-02341066 and PF-00299804 for Advanced Non-Small Cell Lung Cancer

NCT01441128 | Terminated Phase 1

• 2 other identifiers: 11025011-C-0250
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- PF-02341066 and PF-00299804 are drugs that specifically target certain proteins that may be more active in cancer cells than normal cells, in particular in non-small cell lung cancer. Both drugs seem to be able to stop the growth of or kill cancer cells. Researchers want to combine them to see if they are a safe and effective treatment for advanced non-small cell lung cancer. Objectives: \- To test the safety and effectiveness of PF-02341066 and PF-00299804 for advanced non-small cell lung cancer. Eligibility: \- Individuals at least 18 years of age with advanced non-small cell lung cancer that has not responded to standard treatments. Design:

• Participants will be screened with a medical history and physical exam. They will also have blood and urine tests, and imaging studies. Heart and lung function tests and an eye exam may also be given.
• The first cycle of treatment will be 28 days. Every cycle after the first will be 21 days. Participants may have up to 17 cycles of treatment.
• Participants will take both study drugs as tablets. Twelve hours after the first dose, participants will take only the PF-02341066. This dose schedule will remain the same throughout the study.
• Participants will be monitored with frequent blood and urine tests and imaging studies. Tumor biopsies will be taken as needed. Those in the study will keep a diary to record any symptoms or side effects of taking the study drugs.
• After 17 cycles of treatment, or after stopping the study drugs early for any other reason, participants will have a final followup visit.

Conditions

Carcinoma, Non-Small Cell Lung; Adenocarcinoma; Carcinoma, Squamous Cell; Carcinoma, Large Cell

Keywords

Lung Neoplasms; Epithelial-Mesenchymal Transition Factor (c-Met); Tyrosine Kinase Inhibitor; Hepatocyte Growth Factor Receptor; Epidermal Growth Factor Receptor; Non Small Cell Lung Cancer; NSCLC

Outcome Measures

Primary Outcomes (1)

• Overall safety profile of combined PF 02341066 plus PF 00299804 including adverse events (AE), as defined and graded by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], and first cycle Dose Limiting Tox...

  18 months

Secondary Outcomes (4)

• Plasma concentrations and pharmacokinetic (PK) parameters of PF 02341066 and PF 00299804 including AUCtau, Cmax, Ctrough, Tmax, and CLss/F

  18 months

• Clinical activity of combined PF 02341066 plus PF 00299804 including objective response (OR) and stable disease (SD) as defined by RECIST version 1.1, duration of response (DR) and progression free survival (PFS).

  18 months

• Biomarkers in tumor and blood that are potentially predictive for drug activity: for example, KRAS mutations, EGFR mutations (eg, T790M), EGFR and HER2 amplifications, c Met amplification and mutations, ALK, PTEN and PIK3A status in tumor biopsi...

  12 months

• Pharmacodynamic biomarkers in tumor biopsies (e.g., phospho c Met, c Met, EGFR, phospho EGFR) and in blood (e.g., HGF and s Met) that are modulated following drug exposure.

  12 months

Study Arms (2)

Arm 1

EXPERIMENTAL

The starting doses will be 200 mg by mouth, twice a day of PF 02341066 in tablet form and 30 mg by mouth once a day of PF 0029804 in tablet form. Thedose of each drug in the combination will be escalated or de-escalated until the maximum tolerated combined dose is reached. Patients will then be treated with the maximum tolerated combined dose.

Drug: PF-02341066/PF-00299804

Arm 2

EXPERIMENTAL

45 mg by mouth once a day of PF-00299804 in tablet form until progressive disease and then the maximum tolerated combined dose of PF-02341066 (given by mouth twice a day in tablet form) and PF-00299804 (given by mouth once a day in tablet form).

Drug: PF-02341066/PF-00299804

Interventions

PF-02341066/PF-00299804 DRUG

Combined PF-02341066 and PF-00299804

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator s study team before subjects are included in the study.
• Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
• Subjects must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Disease Criteria:
• Dose Escalation Phase: Histologically proven diagnosis of NSCLC that is locally advanced or metastatic, after failure of either at least one prior chemotherapy regimen or targeted therapy.
• Expansion Phase: Histologically proven diagnosis of NSCLC that is locally advanced or metastatic and with acquired resistance to erlotinib or gefitinib. Acquired resistance is defined as progression following either an initial response (complete or partial), or stable disease for at least six months, while on single agent erlotinib or single agent gefitinib. In addition to these patients, Cohort 2 will also enroll patients from ongoing trials, including A7471017 and A7471028, who have progressed on single agent PF-00299804.
• For the dose escalation phase, any prior treatment (chemotherapy, targeted therapy, radiation or surgery) must have been completed at least 2 weeks prior to initiation of study medication, except patients being treated with single agent PF-02341066 will have the option of continuing single agent PF-02341066 until the combination of PF- 02341066 and PF-00299804 is given. For the expansion phase, patients must not have had any intervening treatmen (chemotherapy, targeted therapy, radiation or surgery) between single agent erlotinib or single agent gefitinib treatment, and biopsy and dosing with study drug, unless agreed by the sponsor. In Expansion Cohort 2, patients who have received PF-00299804 as part of an ongoing clinical trial will continue with single agent therapy with PF-00299804 at their current dose after documentation of progression until the combination is given.
• Any acute toxicity from prior treatment must have been recovered to less than or equal to Grade 1 (except alopecia).
• At least 1 target lesion used for assessment of antitumor activity must be measurable by RECIST (version 1.1), or considered evaluable by agreement between the investigator and the sponsor.
• Target lesions can be chosen from a previous irradiated area if lesions in those areas have documented progression.
• Female or male, 18 years of age or older.
• ECOG (Zubrod) performance status 0-2.
• Adequate organ function as defined by the following criteria measured within 7 days prior to enrollment.
• Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) less than or equal to 2.5 times upper limit of normal (ULN), or AST and ALT less than or equal to 5 times ULN if liver function abnormalities are due to underlying malignancy;
• Total serum bilirubin less than or equal to 1.5 times ULN (except patients with documented Gilbert s syndrome);

You may not qualify if:

• Subjects presenting with any of the following will not be included in the study:
• Participation in other studies or treatment within 2 weeks before the current study begins and/or during study participation (with the exception of patients who are receiving single agent PF-00299804 and who enroll into Expansion Cohort 2 from ongoing trials including A7471017 and A7471028, and with the exception of patients being treated with single agent PF-02341066 treatment who enroll during the dose escalation phase and exercise the option of continuing single agent PF-02341066 treatment until the combination of PF-02341066 and PF-00299804 is given) to allow for recovery and drug wash-out.
• Known interstitial fibrosis or interstitial lung disease.
• Patients with known brain metastases who are neurologically stable (asymptomatic) for at least 2 weeks and with no ongoing requirement for corticosteroids may enroll on study before treatment of brain metastases.
• History of carcinomatous meningitis, or leptomeningeal disease.
• Any of the following within 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack.
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes). Diagnosed or suspected congenital long QT syndrome. Ongoing cardiac dysrhythmias of Grade greater than or equal to 2 (CTCAE version 4.02), uncontrolled atrial fibrillation of any grade, or QTc interval \>470 msec.
• Hypertension that cannot be controlled by medications (\>150/100 mmHg despite optimal medical therapy).
• Patient must not have had major surgery or trauma within 28 days prior to enrollment.
• Active uncontrolled infection.
• Pregnant or lactating females.
• Significant gastrointestinal condition that may impair intake, transit, absorption or ability to tolerate investigational drugs.
• Prior malignancy (other than NSCLC): patients will not be eligible if they have evidence of active malignancy (other than non-melanoma skin cancer or in situ cervical cancer, or localized and presumed cured prostate cancer with PSA \< ULN) within the last 3 years.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
• Use of drugs or foods that are known potent CYP3A4 inhibitors within 7 days prior to the first dose of study medication, including but not limited to itraconazole, ketoconazole, miconazole, clarithromycin, erythromycin, indinavir, nefazodone, amprenavir, delavirdine, nelfinavir, ritonavir, saquinavir, diltiazem, verapamil and grapefruit juice.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Alberola V, Camps C, Provencio M, Isla D, Rosell R, Vadell C, Bover I, Ruiz-Casado A, Azagra P, Jimenez U, Gonzalez-Larriba JL, Diz P, Cardenal F, Artal A, Carrato A, Morales S, Sanchez JJ, de las Penas R, Felip E, Lopez-Vivanco G; Spanish Lung Cancer Group. Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer: a Spanish Lung Cancer Group phase III randomized trial. J Clin Oncol. 2003 Sep 1;21(17):3207-13. doi: 10.1200/JCO.2003.12.038.

  PMID: 12947054 BACKGROUND

• Kelly K, Crowley J, Bunn PA Jr, Presant CA, Grevstad PK, Moinpour CM, Ramsey SD, Wozniak AJ, Weiss GR, Moore DF, Israel VK, Livingston RB, Gandara DR. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non--small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 2001 Jul 1;19(13):3210-8. doi: 10.1200/JCO.2001.19.13.3210.

  PMID: 11432888 BACKGROUND

• Scagliotti GV, De Marinis F, Rinaldi M, Crino L, Gridelli C, Ricci S, Matano E, Boni C, Marangolo M, Failla G, Altavilla G, Adamo V, Ceribelli A, Clerici M, Di Costanzo F, Frontini L, Tonato M; Italian Lung Cancer Project. Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol. 2002 Nov 1;20(21):4285-91. doi: 10.1200/JCO.2002.02.068.

  PMID: 12409326 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Adenocarcinoma; Carcinoma, Squamous Cell; Carcinoma, Large Cell; Lung Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Study Officials

• Arun Rajan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2011
• First Posted: September 27, 2011
• Study Start: September 1, 2011
• Primary Completion: February 28, 2014
• Study Completion: February 26, 2015
• Last Updated: December 17, 2019

Record last verified: 2015-02-26

Locations

US (1)