NCT01465802|CompletedPhase 2Results

Study Of Dacomitinib (PF-00299804) In Advanced NSCLC Patients (Post Chemo Or Select First Line) To Evaluate Prophylactic Intervention On Derm And GI AEs And PRO

ARCHER 1042

ARCHER 1042: A PHASE 2 STUDY OF DACOMITINIB IN ADVANCED NON-SMALL CELL LUNG CANCER (POST-CHEMOTHERAPY OR SELECT FIRST LINE PATIENTS) TO EVALUATE PROPHYLACTIC INTERVENTION ON DERMATOLOGIC AND GASTROINTESTINAL ADVERSE EVENTS AND PATIENT REPORTED OUTCOMES

Pfizer ClinicalTrials.gov

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1 other identifier

A7471042

Study Type

interventional

Target

236

Locations

2 countries

Sites

Timeline

RegisteredNov 2011

StartedDec 2011

CompletionMay 2015

Brief Summary

To assess the impact of prophylactic treatment on the incidence of adverse events in advanced NSCLC patients (post chemotherapy) treated with dacomitinib daily as a single agent. To assess the impact of an interrupted dacomitinib dosing schedule in Cycle 1 on the incidence of adverse events in first-line advanced NSCLC patients with an EGFR mutation (HER-1 mutation, HER-2 mutation or HER-2 amplification).

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

236

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started Dec 2011

Typical duration for phase_2

Geographic Reach

2 countries

81 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

3.4 years study duration

First Submitted

Initial submission to the registry

October 20, 2011

Completed

18 days until next milestone

First Posted

Study publicly available on registry

November 7, 2011

Completed

2 months until next milestone

Study Start

First participant enrolled

December 26, 2011

Completed

3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 18, 2015

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 18, 2015

Completed

1.3 years until next milestone

Results Posted

Study results publicly available

August 17, 2016

Completed

Last Updated

January 9, 2019

Status Verified

December 1, 2018

Enrollment Period

3.4 years

First QC Date

October 20, 2011

Results QC Date

April 15, 2016

Last Update Submit

December 20, 2018

Conditions

Non Small Cell Lung Cancer (NSCLC)

Keywords

non-small cell lung canceradvancedpreviously treated

Outcome Measures

Primary Outcomes (11)

Percentage of Participants With Select Dermatologic Adverse Events of Interest (SDAEI) (All Causality, All Grade) in the First 8 Weeks of Treatment by Treatment Arm for Cohort I
SDAEI of all causality and all grades were evaluated in participants in Cohort I. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer. 95% confidence interval (CI) calculated using exact method based on binomial distribution. After protocol amendment 1, Arm C was removed from Cohort I and enrollment to Arm C was terminated. Only 7 participants were enrolled in Cohort I Arm C as a result. Given the smaller sample size, analyse of Outcome Measure 1 was not conducted in Cohort I Arm C.
First 8 Weeks of Treatment
Percentage of Participants With SDAEI (All Causality, Grade Greater Than or Equal to [≥] 2) in the First 8 Weeks of Treatment by Treatment Arm for Cohort I
SDAEI of all causality and Grade ≥2 were evaluated in participants in Cohort I. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer. Adverse events (AEs) were graded for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 4.0). 95% CI calculated using exact method based on binomial distribution. After protocol amendment 1, Arm C was removed from Cohort I and enrollment to Arm C was terminated. Only 7 participants were enrolled in Cohort I Arm C as a result. Given the smaller sample size, analyse of Outcome Measure 2 was not conducted in Cohort I Arm C.
First 8 Weeks of Treatment
Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) by Treatment Arm for Cohort I
Patient Reported Outcomes (PROs) of Health Related Quality of Life (HRQoL) \& disease/treatment-related symptoms were assessed using Dermatologic Survey (Skindex-16) that assesses "bother". It includes 3 multi-item scales: symptoms, emotions \& functioning. Individual scaled scores \& total scores were determined. Skindex questions were transformed to a linear scale of 0 (never bothered) to 100 (always bothered). Subscale scores are an average of non-missing questions in a given scale if greater than (\>) 75% of total subscale questions are non-missing. The Total Score is an average of all non-missing questions in the Skindex if \>75% of total questions are non-missing. A negative change score represents a better quality of life. A change score of 10 points is considered clinically significant. Skindex completion criteria were defined as completion of 3 out of 4 items for questions 1 to 4, 6 out of 7 items for questions 5 to 11, 4 out of 5 items for questions 12 to 16 for the visit.
First 8 Weeks of Treatment
Percentage of Participants With Diarrhea AEs (All Causality, All Grade and Grade ≥2) in the First 8 Weeks of Treatment for Cohort II
Diarrhea AEs of all causality, all grade and Grade ≥2 were evaluated in participants in Cohort II. AEs were graded for severity using the NCI-CTCAE, Version 4.0. 95% CI calculated using exact method based on binomial distribution.
First 8 Weeks of Treatment
Mean Change From Baseline (Cycle 1 Day 1) Modified Oral Mucositis Daily Questionnaire (OMDQ) Scores (Mouth and Throat Soreness Categories and Scale, and Diarrhea Categories and Scale) for Cohort II
Diarrhea severity was assessed using the modified-OMDQ. This questionnaire is comprised of 6 questions in total; however, only two items relate to diarrhea symptoms (item 5 and item 6). Symptoms scores were developed for both the full questionnaire and for the diarrhea-only questions for each completed survey. Mucositis questions were transformed to a score range of 0 to 10. Increasing OMDQ values are associated with greater symptom burden. Modified OMDQ completion criteria were defined as completion of all 4 questions (questions 2, 4, 5 and 6). M/T = mouth and throat.
Cycles 1, 2, 3, 4, 5, and 6, EoT and Follow-up
Percentage of Participants With SDAEI (All Causality, All Grade) in the First 8 Weeks of Treatment for Cohort II
SDAEI of all causality and all grades were evaluated in participants in Cohort II. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer. 95% CI calculated using exact method based on binomial distribution.
First 8 Weeks of Treatment
Percentage of Participants With SDAEI (All Causality, Grade ≥2) in the First 8 Weeks of Treatment for Cohort II
SDAEI of all causality and Grade ≥2 were evaluated in participants in Cohort II. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer. AEs were graded for severity using the NCI-CTCAE, Version 4.0. 95% CI calculated using exact method based on binomial distribution.
First 8 Weeks of Treatment
Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II
PROs of HRQoL and disease/treatment-related symptoms were assessed using Dermatologic Survey (Skindex-16) that assesses "bother". It includes 3 multi-item scales: symptoms, emotions \& functioning. Individual scaled scores \& total scores were determined. Skindex questions were transformed to a linear scale of 0 (never bothered) to 100 (always bothered). Subscale scores are an average of non-missing questions in a given scale if \> 75% of total subscale questions are non-missing. The Total Score is an average of all non-missing questions in the Skindex if \>75% of total questions are non-missing. A negative change score represents a better quality of life. A change score of 10 points is considered clinically significant. Skindex completion criteria were defined as completion of 3 out of 4 items for questions 1 to 4, 6 out of 7 items for questions 5 to 11, 4 out of 5 items for questions 12 to 16 for the visit.
Cycles 1, 2, 3, 4, 5, and 6, EoT and Follow-up
Mean Area Under the Plasma Concentration Time Curve From 0 to 24 Hours (AUC0-24) and From 0 to 120 Hours (AUC0-120) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III
AUC0-24 is the area under the plasma concentration-time curve (AUC) from time 0 to 24 hours post-dose. AUC0-120 is the AUC from time 0 to 120 hours post-dose. AUC was calculated by the linear trapezoidal method using a non-compartmental pharmacokinetic (PK) analysis. ng\*hr/mL = nanogram hours per milliliter
Cycle 1 Day 10: Pre-dose and 2, 4, 6, 24, 48, 72, 96, and 120 hours post-dose (the 120 hour sample was obtained on Day 15 pre-dose).
Mean Maximum Observed Plasma Concentrations (Cmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III
Cmax was obtained from direct inspection of the data. ng/mL = nanograms per milliliter
Cycle 1 Day 10: Pre-dose and 2, 4, 6, 24, 48, 72, 96, and 120 hours post-dose (the 120 hour sample was obtained on Day 15 pre-dose).
Median Time of Occurrence of Cmax (Tmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III
Tmax was obtained from direct inspection of the data as the time of first occurence of Cmax.
Cycle 1 Day 10: Pre-dose and 2, 4, 6, 24, 48, 72, 96, and 120 hours post-dose (the 120 hour sample was obtained on Day 15 pre-dose).

Secondary Outcomes (7)

Percentage of Participants Receiving Any Concomitant Drug or Non-Drug Treatment for SDAEI, Diarrhea and Mucositis for Cohort I by Treatment Arm, Cohort II, and Cohort III
Screening to the Post-Teatment Follow-Up Visit (at least 28 days and no more than 35 days after the end of dacomitinib treatment due to progression of disease, intolerance to dacomitinib treatment, or participant withdrawal)
Mean AUC From 0 to the End of the Dosing Interval (AUC0-tau) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I
Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Mean Cmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I
Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Median Tmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I
Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Mean Apparent Clearance (CL/F) for Dacomitinib on Cycle 2 Day 1 for Cohort I
Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
+2 more secondary outcomes

Study Arms (3)

Cohort I

EXPERIMENTAL

Arm A: Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent Doxycycline placebo orally BID for 4 weeks Arm B: Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent Doxycycline 100 mg orally BID for 4 weeks

Drug: DacomitinibDrug: Doxycycline

Cohort II

EXPERIMENTAL

Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent Topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks VSL#3 probiotic 4 capsules orally daily or 1 sachet orally daily for up to 5 weeks (starting between Day minus 7 to Day minus 4 and continuing through Day 28)

Drug: DacomitinibDrug: ProbioticDrug: Alclometasone cream

Cohort III

EXPERIMENTAL

Cohort III is an interrupted dosing schedule of dacomitinib in the first cycle only

Drug: Dacomitinib

Interventions

DacomitinibDRUG

Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent

Cohort ICohort II

DoxycyclineDRUG

Doxycycline or Doxycycline placebo BID for 4 weeks

Cohort I

ProbioticDRUG

VSL#3 probiotic 4 capsules orally daily or 1 sachet orally daily for up to 5 weeks (starting between Day minus 7 to Day minus 4 and continuing through Day 28)

Cohort II

Alclometasone creamDRUG

Topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks

Cohort II

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Advanced Non-Small Cell Lung Cancer (NSCLC).
For Cohort I and Cohort II, advanced NSCLC patients must have received at least one prior regimen of systemic therapy which includes at least one standard chemotherapy for advanced NSCLC and who have failed (ie, progressed or intolerant due to toxicity which precludes further treatment) standard therapy for advanced or metastatic disease. To be considered intolerant to treatment, a patient must have received at least two cycles to be considered previously treated.
For Cohort III, advanced NSCLC patients must not have received prior systemic treatment for their advanced disease and require a known EGFR (HER-1) mutation, HER-2 mutation or HER-2 amplification. Cohort III patients could have received prior adjuvant chemotherapy for Stage I-III disease or combined modality chemotherapy-radiation for Stage IIIA disease is allowed if treatment completed\>12 months prior to enrollment.
All cohorts, patients must have evidence of disease; however, measurable disease is not required to enroll.
Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
Estimated creatinine clearance ≥15 mL/min.

You may not qualify if:

Prior treatment with an EGFR-targeted or HER-targeted agent (all cohorts).
Chemotherapy, radiotherapy, biological or investigational agents within 2 weeks of baseline disease assessments (all cohorts).
Patients with known diffuse interstitial lung disease (all cohorts).
Investigational therapy as only treatment for advanced NSCLC without administration of an approved chemotherapy for advanced NSCLC (for Cohort I and Cohort II)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Pfizerlead

Study Sites (81)

City of Hope

Duarte, California, 91010, United States

Location

St. Jude Heritage Healthcare

Fullerton, California, 92835, United States

Location

UCLA Hematology Oncology

Irvine, California, 92604, United States

Location

UC San Diego Medical Center - La Jolla

La Jolla, California, 92037, United States

Location

UC San Diego Moores Cancer Center - Investigational Drug Services

La Jolla, California, 92037, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Drug Management Only: UCLA West Medical Pharmacy

Los Angeles, California, 90095-7349, United States

Location

Drug Management Only: UCLA West Medical Pharmacy Attn: Steven L. Wong, Pharm.D.