A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer

NCT00585195 | Completed Phase 1 Results

• 2 other identifiers: A8081001PROFILE 1001
• Study Type: interventional
• Target: 596
• Locations: 4 countries
• Sites: 29

Brief Summary

PF-02341066 may work in cancer by blocking the cell growth, migration and invasion of tumor cells. PF-02341066 is a new class of drugs called c-Met/Hepatocyte growth factor receptor tyrosine kinase inhibitors. This compound is also an inhibitor of the anaplastic lymphoma kinase (called ALK) tyrosine kinase and ROS receptor tyrosine kinases. This research study is the first time PF-02341066 will be given to people. PF-02341066 is taken by mouth daily.

Conditions

Non-Small Cell Lung Cancer ALK-positive; Non-Small Cell Lung Cancer c-Met Dependent; Non-Small Cell Lung Cancer ROS Marker Positive; Systemic Anaplastic Large-Cell Lymphoma; Advanced Malignancies Except Leukemia

Keywords

Crizotinib; dose-finding; drug-drug interaction; ALK rearrangements; c-Met mutations or amplifications; c-Met dependent tumors; ROS1 rearrangements; c-Met exon 14 deletion; c-Met exon 14 skipping; c-Met exon 14 alterations

Outcome Measures

Primary Outcomes (53)

• Dose-Escalation Cohort: Maximum Tolerated Dose (MTD) of Crizotinib

  MTD: Dose level at which at most 1 of 6 participants experienced DLT within and including 28 days of treatment (during Cycle 1 \[1 cycle=28 days\]) with next higher dose having at least 2/3 or 2/6 participants experiencing a DLT. DLT was defined as any of following: Hematologic toxicities- 1) prolonged grade 4 neutropenia for \>7 days. 2) Febrile neutropenia: grade 4 neutropenia with fever greater than (\>) 38.5 degree Celsius, both sustained over a 24 hour period (3) neutropenic infection: greater than or equal to (\>=) Grade 3 neutropenia with Grade \>=3 infection. (4) Grade \>=3 thrombocytopenia with bleeding/grade 4 lasting \>=7 days. Other non-hematologic toxicity included: Grade 3/4 toxicities (except for alopecia, Grade 3/4 hypophosphatemia, grade 3 hypertension with controlled blood pressure \[less than (\<) 140/90 millimeter of mercury, and Grade 3/4 hyperuricemia without signs and symptoms of gout). Nausea, vomiting/diarrhea must persist at grade 3/4 despite maximal medical therapy.

  Cycle 1 (28 days)

• Dose-Escalation Cohort: Recommended Phase 2 Dose (RP2D) of Crizotinib

  RP2D was defined as a dose below or equal to MTD, at which crizotinib was unlikely to cause a significant inhibition of CYP3A4 activity.

  Cycle 1 (28 days)

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Crizotinib on Day -7

  AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) extrapolated to infinite time (0-inf).

  Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Day -7

  Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

  Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 1 Day 1

  Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

  Pre-dose, 2, 4 and 6 hours post dose on Cycle 1 Day 1

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 1 Day 15

  Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

  Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 2 Day 1

  Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

  Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 2 Day 1

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Trough Concentration (Ctrough) of Crizotinib Cycle 1 Day 15

  Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

  Pre-dose on Cycle 1 Day 15

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Trough Concentration (Ctrough) of Crizotinib on Cycle 2 Day 1

  Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

  Pre-dose on Cycle 2 Day 1

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Day -7

  Cmax is defined as the observed maximum plasma concentration post drug administration.

  Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 1 Day 1

  Cmax is defined as the observed maximum plasma concentration post drug administration.

  Pre-dose, 2, 4 and 6 hours post dose on Cycle 1 Day 1

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 1 Day 15

  Cmax is defined as the observed maximum plasma concentration post drug administration.

  Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 2 Day 1

  Cmax is defined as the observed maximum plasma concentration post drug administration.

  Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 2 Day 1

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Day -7

  Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

  Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Cycle 1 Day 1

  Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

  Pre-dose, 2, 4 and 6 hours post dose on Cycle 1 Day 1

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Cycle 1 Day 15

  Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

  Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib Cycle 2 Day 1

  Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

  Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 2 Day 1

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Plasma Decay Half-Life (t1/2) of Crizotinib on Day -7

  Plasma decay half-life is the time measured for the plasma concentration of Crizotinib to decrease by one half.

  Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7

• Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Number of Participants With Treatment Emergent Adverse Events (TEAES) and Serious Adverse Events (SAEs)

  An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. AEs included both serious and all non-serious adverse events. TEAEs were those with initial onset or increasing in severity on or after the first dose of investigational product administration.

  up to 189 Months

• Dose-Escalation Cohort: Number of Participants With Dose-limiting Toxicities (DLT)

  Dose-limiting toxicity (DLT) was defined as any of the following: Hematologic- prolonged grade 4 neutropenia for \>7 days. Febrile neutropenia, defined as grade 4 neutropenia with fever greater than (\>)38.5 degree Celsius, both sustained over a 24 hour period, neutropenic infection: greater than or equal to (\>=)Grade 3 neutropenia with Grade \>=3 infection. Grade \>=3 thrombocytopenia with bleeding or grade 4 lasting \>=7 days Lymphopenia was not considered a DLT unless accompanied by infection. Other non-hematologic toxicity: Grade 3 or 4 toxicities (except for alopecia, Grade 3/4 hypophosphatemia, grade 3 hypertension with controlled blood pressure \[less than (\<) 140/90\], and Grade 3/4 hyperuricemia without signs and symptoms of gout). Nausea, vomiting or diarrhea must persist at grade 3 or 4 despite maximal medical therapy.

  Cycle 1 (28 days)

• Midazolam Interaction Cohort: Maximum Observed Plasma Concentration (Cmax) of Midazolam When Taken Alone or Taken With Crizotinib

  Cmax is defined as the observed maximum plasma concentration post drug administration.

  pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Day -7 (midazolam alone arm), pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Cycle 2 Day 1 (midazolam with crizotinib arm)

• Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Midazolam When Taken Alone or Taken With Crizotinib

  AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).

  pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Day -7 (midazolam alone arm), pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Cycle 2 Day 1 (midazolam with crizotinib arm)

• RP2D Cohort: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Crizotinib When Taken With Food

  AUC0-24 of Crizotinib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.

  pre-dose, 1, 2, 4, 6, 8, 9, and 24 hours post-dose on Day -7

• RP2D Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib When Taken With Food

  Cmax is defined as the observed maximum plasma concentration post drug administration.

  pre-dose, 1, 2, 4, 6, 8, 9, and 24 hours post-dose on Day -7

• Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib Alone and When Taken With Rifampin

  Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau).

  pre-dose, 2, 4, 6, 8 and 10 hours on Cycle 1 Day 15 (Crizotinib alone arm) and Cycle 2 Day 1 (Crizotinib with Rifampin arm)

• Rifampin Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib Alone and When Taken With Rifampin

  pre-dose, 2, 4, 6, 8 and 10 hours on Cycle 1 Day 15 (Crizotinib alone) and Cycle 2 Day 1 (Crizotinib with Rifampin)

• Rifampin Cohort: Ctrough of Crizotinib Alone and When Taken With Rifampin

  Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

  pre-dose on Cycle 1 Day 15 (Crizotinib alone arm) and Cycle 2 Day 1 (Crizotinib with Rifampin arm)

• Itraconazole Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib When Taken Alone and When Taken With Itraconazole

  Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 24 hours.

  pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15 (Crizotinib with itraconazole) and Cycle 2 Day 1 (itraconazole alone)

• Itraconazole Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib When Taken Alone and When Taken With Itraconazole

  pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15 (Crizotinib with itraconazole) and Cycle 2 Day 1 (itraconazole alone)

• Itraconazole Cohort: Trough Plasma Concentration (Ctrough) of Crizotinib When Taken Alone and When Taken With Itraconazole

  Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

  pre-dose on Cycle 1 Day 15 (crizotinib with itraconazole) and Cycle 2 Day 1 (itraconazole alone)

• Recommended Phase 2 Dose (RP2D) Cohort: Percentage of Participants With Objective Response (OR)

  ORR was defined as participants with a best overall response of complete response (CR) or partial response (PR) divided by the total number of evaluable participants per RECIST version 1.0 (RECIST1.1 for ALK-negative NSCLC cohort 1 and ALK-negative NSCLC cohort 2). CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response. PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response.

  Baseline up to 172 months

• Recommended Phase 2 Dose (RP2D) Cohort: Duration of Response (DOR)

  Duration of response (DoR) was the time from first documentation of PR or CR to date of first documentation of progressive disease (PD) or death due to any cause. PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response. CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response. PD: \>=20% increase in the sum of the longest diameter of target lesions taking as references the smallest sum longest diameter recorded since the treatment started, unequivocal progression of existing non-target lesions, or the appearance of 1 or more new lesions.

  From first documentation of response to date of PD or death due to any cause (up to 172 months)

• Recommended Phase 2 Dose (RP2D) Cohort: Time to Response (TTR)

  TTR: time between first dose until first documented response of PR or CR. PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response. CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response.

  From first dose until first documented response of PR or CR (up to 172 months)

• Recommended Phase 2 Dose (RP2D) Cohort: Percentage of Participants With Disease Control at Week 8

  Disease control was defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) per RECIST version 1.0 (RECIST1.1 for ALK-negative NSCLC cohort 1 and ALK-negative NSCLC cohort 2). PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response. CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  Week 8

• Recommended Phase 2 Dose (RP2D) Cohort: Percentage of Participants With Disease Control at Week 16

  Disease control was defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) per RECIST version 1.0 (RECIST1.1 for ALK-negative NSCLC cohort 1 and ALK-negative NSCLC cohort 2). PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response. CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  Week 16

• Recommended Phase 2 Dose (RP2D) Cohort: Progression Free Survival (PFS)

  Progression free survival (PFS) was the time from randomization date to date of first documentation of PD or death due to any cause RECIST version 1.0 (RECIST1.1 for ALK-negative NSCLC cohort 1 and ALK-negative NSCLC cohort 2). PD: \>=20% increase in the sum of the longest diameter of target lesions taking as references the smallest sum longest diameter recorded since the treatment started, unequivocal progression of existing non-target lesions, or the appearance of 1 or more new lesions.

  From randomization until PD or death, whichever occurred first (up to 172 months)

• Recommended Phase 2 Dose (RP2D) Cohort: Probability of Being Event Free at Month 6

  Probability of being event free (event defined as PD or death due to any cause) at 6 months after the first dose of crizotinib was reported. PD: \>=20% increase in the sum of the longest diameter of target lesions taking as references the smallest sum longest diameter recorded since the treatment started, unequivocal progression of existing non-target lesions, or the appearance of 1 or more new lesions.

  From randomization to 6 months

• Recommended Phase 2 Dose (RP2D) Cohort: Overall Survival (OS)

  OS was defined as the time from randomization to death due to any cause.

  From randomization date to the date of death (up to 172 Months)

• Probability of Participant Survival at Month 6

  Probability of survival was defined as the probability of being alive at Month 6.

  Month 6

• Probability of Participant Survival at Month 12

  Probability of survival was defined as the probability of being alive at Month 12.

  Month 12

• Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 1 Day 15

  Geometric mean of ratio (Cycle1Day15/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.

  Baseline, Cycle 1 Day 15

• Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 2 Day 1

  Geometric mean of ratio (Cycle 2 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.

  Baseline, Cycle 2 Day 1

• Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 4 Day 1

  Geometric mean of ratio (Cycle 4 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.

  Baseline, Cycle 4 Day 1

• Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 6 Day 1

  Geometric mean of ratio (Cycle 6 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.

  Baseline, Cycle 6 Day 1

• Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 9 Day 1

  Geometric mean of ratio (Cycle 9 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

  Baseline, Cycle 9 Day 1

• Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 12 Day 1

  Geometric mean of ratio (Cycle 12 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

  Baseline, Cycle 12 Day 1

• Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 15 Day 1

  Geometric mean of ratio (Cycle 15 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

  Baseline, Cycle 15 Day 1

• Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 18 Day 1

  Geometric mean of ratio (Cycle 18 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

  Baseline, Cycle 18 Day 1

• Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 21 Day 1

  Geometric mean of ratio (Cycle 21 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

  Baseline, Cycle 21 Day 1

• Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 24 Day 1

  Geometric mean of ratio (Cycle 24 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

  Baseline, Cycle 24 Day 1

• Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 27 Day 1

  Geometric mean of ratio (Cycle 27 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

  Baseline, Cycle 27 Day 1

• Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 30 Day 1

  Geometric mean of ratio (Cycle 30 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

  Baseline, Cycle 30 Day 1

• Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at End of Treatment

  Geometric mean of ratio (End of treatment/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

  Baseline, End of Treatment (28 days post last dose)

Study Arms (1)

1

EXPERIMENTAL

Drug: PF-02341066; Drug: Rifampin; Drug: Itraconazole

Interventions

PF-02341066 DRUG

Escalating doses of PF-02341066 will be administered orally on a continuous dosing schedule. Doses to be evaluated will range from 50 mg to 2000 mg/day administered either once or twice a day. A treatment cycle is considered to be 28 days (or 21 days depending on the cohort).

1

Rifampin DRUG

600 mg QD administered from Cycle 1, Day 16 to Cycle 2, Day 1 (14 days of dosing) in combination with PF-02341066.

1

Itraconazole DRUG

Multiple Dose Design: 200 mg QD administered from Cycle 1, Day 1 to Cycle 1, Day 16 (16 days) in combination with PF-02341066.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced malignancies (except leukemias), histologically proven at diagnosis; Histologically confirmed advanced malignancies that are known to be sensitive to PF-03241066 inhibition, e.g. ALK, c-MET and ROS
• Solid tumors must have measurable disease (Recommended Phase 2 Dose Cohort patients with non-measurable disease may enter on a case-by-case basis); not required for DDI sub-studies.
• Adequate blood cell counts, kidney function, liver function and Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 (for the Recommended Phase 2 Cohort, a ECOG score of 2 may be allowed on a case-by-case basis)

You may not qualify if:

• Major surgery, radiation therapy or anti-cancer therapy within 2 to 4 weeks of starting study treatment, depending on the patient cohort
• Prior stem cell transplant except of patients with neuroblastoma, lymphoma or myeloma
• Active or unstable cardiac disease or heart attack within 3 months of starting study treatment

Sponsors & Collaborators

• Pfizer: lead

Study Sites (29)

University of California, Irvine Medical Center

Orange, California, 92868-3201, United States

Location

University of Colorado Hospital/ Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Ophthalmic Consultants of Boston Inc.

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Center

Boston, Massachusetts, 02215, United States

Location

Joslin Beetham Eye Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Kresge Eye Institute

Detroit, Michigan, 48201, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10022, United States

Location

Memorial Sloan Kettering Cancer Center: Breast and Imaging Center

New York, New York, 10065, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

UNC Hospitals

Chapel Hill, North Carolina, 27599-7600, United States

Location

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

Location

Ohio State Eye and Ear Institute

Columbus, Ohio, 43212, United States

Location

The Ohio State University Martha Morehouse Medical Plaza

Columbus, Ohio, 43221, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Henry-Joyce Cancer Clinic

Nashville, Tennessee, 37232, United States

Location

Vanderbilt Eye Institute

Nashville, Tennessee, 37232, United States

Location

The University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

The University of Vermont Cancer Center

Burlington, Vermont, 05405, United States

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Aichi cancer center central hospital

Nagoya, Aichi-ken, 464-8681, Japan

Location

Hyogo Cancer Center

Akashi, Hyōgo, 673-8558, Japan

Location

Kindai University Hospital

Sayama, Osaka, 589-8511, Japan

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Related Publications (18)

• Ng TL, Tsui DCC, Wang S, Usari T, Patil T, Wilner K, Camidge DR. Association of anticoagulant use with clinical outcomes from crizotinib in ALK- and ROS1-rearranged advanced non-small cell lung cancers: A retrospective analysis of PROFILE 1001. Cancer Med. 2022 Dec;11(23):4422-4429. doi: 10.1002/cam4.4789. Epub 2022 May 5.

  PMID: 35510711 DERIVED

• Camidge DR, Otterson GA, Clark JW, Ignatius Ou SH, Weiss J, Ades S, Shapiro GI, Socinski MA, Murphy DA, Conte U, Tang Y, Wang SC, Wilner KD, Villaruz LC. Crizotinib in Patients With MET-Amplified NSCLC. J Thorac Oncol. 2021 Jun;16(6):1017-1029. doi: 10.1016/j.jtho.2021.02.010. Epub 2021 Mar 4.

  PMID: 33676017 DERIVED

• Solomon BJ, Kim EE, Winter M, Monti K, Tang Y, Wilner KD, Wang S, Ou SI. Ophthalmological assessment of crizotinib in advanced non-small-cell lung cancer. Lung Cancer. 2020 Jul;145:167-172. doi: 10.1016/j.lungcan.2020.04.010. Epub 2020 Apr 28.

  PMID: 32460197 DERIVED

• Clark JW, Camidge DR, Kwak EL, Maki RG, Shapiro GI, Chen I, Tan W, Randolph S, Christensen JG, Ozeck M, Tang Y, Wilner KD, Salgia R. Dose-escalation trial of the ALK, MET & ROS1 inhibitor, crizotinib, in patients with advanced cancer. Future Oncol. 2020 Jan;16(1):4289-4301. doi: 10.2217/fon-2019-0653. Epub 2019 Nov 28.

  PMID: 31778074 DERIVED

• Shaw AT, Riely GJ, Bang YJ, Kim DW, Camidge DR, Solomon BJ, Varella-Garcia M, Iafrate AJ, Shapiro GI, Usari T, Wang SC, Wilner KD, Clark JW, Ou SI. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann Oncol. 2019 Jul 1;30(7):1121-1126. doi: 10.1093/annonc/mdz131.

  PMID: 30980071 DERIVED

• Camidge DR, Kim EE, Usari T, Polli A, Lewis I, Wilner KD. Renal Effects of Crizotinib in Patients With ALK-Positive Advanced NSCLC. J Thorac Oncol. 2019 Jun;14(6):1077-1085. doi: 10.1016/j.jtho.2019.02.015. Epub 2019 Feb 26.

  PMID: 30822515 DERIVED

• Yoneda KY, Scranton JR, Cadogan MA, Tassell V, Nadanaciva S, Wilner KD, Stollenwerk NS. Interstitial Lung Disease Associated With Crizotinib in Patients With Advanced Non-Small Cell Lung Cancer: Independent Review of Four PROFILE Trials. Clin Lung Cancer. 2017 Sep;18(5):472-479. doi: 10.1016/j.cllc.2017.03.004. Epub 2017 Mar 14.

  PMID: 28373069 DERIVED

• Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, Riely GJ, Varella-Garcia M, Shapiro GI, Costa DB, Doebele RC, Le LP, Zheng Z, Tan W, Stephenson P, Shreeve SM, Tye LM, Christensen JG, Wilner KD, Clark JW, Iafrate AJ. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Nov 20;371(21):1963-71. doi: 10.1056/NEJMoa1406766. Epub 2014 Sep 27.

  PMID: 25264305 DERIVED

• Go H, Kim DW, Kim D, Keam B, Kim TM, Lee SH, Heo DS, Bang YJ, Chung DH. Clinicopathologic analysis of ROS1-rearranged non-small-cell lung cancer and proposal of a diagnostic algorithm. J Thorac Oncol. 2013 Nov;8(11):1445-50. doi: 10.1097/JTO.0b013e3182a4dd6e.

  PMID: 24128715 DERIVED

• Awad MM, Katayama R, McTigue M, Liu W, Deng YL, Brooun A, Friboulet L, Huang D, Falk MD, Timofeevski S, Wilner KD, Lockerman EL, Khan TM, Mahmood S, Gainor JF, Digumarthy SR, Stone JR, Mino-Kenudson M, Christensen JG, Iafrate AJ, Engelman JA, Shaw AT. Acquired resistance to crizotinib from a mutation in CD74-ROS1. N Engl J Med. 2013 Jun 20;368(25):2395-401. doi: 10.1056/NEJMoa1215530. Epub 2013 Jun 1.

  PMID: 23724914 DERIVED

• Camidge DR, Bang YJ, Kwak EL, Iafrate AJ, Varella-Garcia M, Fox SB, Riely GJ, Solomon B, Ou SH, Kim DW, Salgia R, Fidias P, Engelman JA, Gandhi L, Janne PA, Costa DB, Shapiro GI, Lorusso P, Ruffner K, Stephenson P, Tang Y, Wilner K, Clark JW, Shaw AT. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012 Oct;13(10):1011-9. doi: 10.1016/S1470-2045(12)70344-3. Epub 2012 Sep 4.

  PMID: 22954507 DERIVED

• Ou SH, Azada M, Dy J, Stiber JA. Asymptomatic profound sinus bradycardia (heart rate </=45) in non-small cell lung cancer patients treated with crizotinib. J Thorac Oncol. 2011 Dec;6(12):2135-7. doi: 10.1097/JTO.0b013e3182307e06.

  PMID: 22088989 DERIVED

• Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA, Shapiro GI, Costa DB, Ou SH, Butaney M, Salgia R, Maki RG, Varella-Garcia M, Doebele RC, Bang YJ, Kulig K, Selaru P, Tang Y, Wilner KD, Kwak EL, Clark JW, Iafrate AJ, Camidge DR. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011 Oct;12(11):1004-12. doi: 10.1016/S1470-2045(11)70232-7. Epub 2011 Sep 18.

  PMID: 21933749 DERIVED

• Kijima T, Takeuchi K, Tetsumoto S, Shimada K, Takahashi R, Hirata H, Nagatomo I, Hoshino S, Takeda Y, Kida H, Goya S, Tachibana I, Kawase I. Favorable response to crizotinib in three patients with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion-type oncogene-positive non-small cell lung cancer. Cancer Sci. 2011 Aug;102(8):1602-4. doi: 10.1111/j.1349-7006.2011.01970.x.

  PMID: 21767331 DERIVED

• Ou SH, Kwak EL, Siwak-Tapp C, Dy J, Bergethon K, Clark JW, Camidge DR, Solomon BJ, Maki RG, Bang YJ, Kim DW, Christensen J, Tan W, Wilner KD, Salgia R, Iafrate AJ. Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification. J Thorac Oncol. 2011 May;6(5):942-6. doi: 10.1097/JTO.0b013e31821528d3.

  PMID: 21623265 DERIVED

• Costa DB, Kobayashi S, Pandya SS, Yeo WL, Shen Z, Tan W, Wilner KD. CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib. J Clin Oncol. 2011 May 20;29(15):e443-5. doi: 10.1200/JCO.2010.34.1313. Epub 2011 Mar 21. No abstract available.

  PMID: 21422405 DERIVED

• Butrynski JE, D'Adamo DR, Hornick JL, Dal Cin P, Antonescu CR, Jhanwar SC, Ladanyi M, Capelletti M, Rodig SJ, Ramaiya N, Kwak EL, Clark JW, Wilner KD, Christensen JG, Janne PA, Maki RG, Demetri GD, Shapiro GI. Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. N Engl J Med. 2010 Oct 28;363(18):1727-33. doi: 10.1056/NEJMoa1007056.

  PMID: 20979472 DERIVED

• Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Janne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28;363(18):1693-703. doi: 10.1056/NEJMoa1006448.

  PMID: 20979469 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic

Interventions

Crizotinib; Rifampin; Itraconazole

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Triazoles; Azoles; Piperazines

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2007
• First Posted: January 3, 2008
• Study Start: April 19, 2006
• Primary Completion: July 30, 2020
• Study Completion: January 19, 2022
• Last Updated: February 8, 2023
• Results First Posted: October 14, 2021

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (24); JP (3); AU (1); KR (1)