A Study Of Dacomitinib (PF-00299804) In Patients With Advanced Non-Small Cell Lung Cancer

NCT01858389 | Completed Phase 2 Results

• 1 other identifier: A7471047
• Study Type: interventional
• Target: 41
• Locations: 2 countries
• Sites: 14

Brief Summary

This is a Phase 2 study of oral dacomitinib given every 12 hours over days 1-4 of each two-week cycle to patients with Non-small cell lung cancer. The study includes two groups of patients, those whose tumor has a documented T790M mutation, and those without this mutation. All patients will receive repeated cycles of dacomitinib until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met.

Conditions

Non-small Cell Lung Cancer

Keywords

Non-small cell lung cancer; T790M mutation. dacomitinib

Outcome Measures

Primary Outcomes (2)

• Best Overall Response (BOR) in Participants With T790M Mutation

  BOR was best response from start of treatment until disease progression, according to the RECIST,v1.1. CR=disappearance of all preexisting lesions except nodal disease, with all nodal lesions decreased to normal size (short axis \<10 mm) and no appearance of new unequivocal malignant lesions. PR= ≥30% decrease from baseline of sum of diameters of all target lesions with no unequivocal progression of preexisting non-target lesions or appearance of new lesions. CR and PR were confirmed on a follow-up imaging assessment ≥4 weeks after the initial response documentation. Progression= ≥20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions. Stable disease=not qualify for CR, PR or progression. BOR was analyzed only for participants with T790M mutation according to the primary study objective.

  From baseline until disease progression, up to 61 weeks.

• Objective Response Rate (ORR) in Participants With T790M Mutation

  ORR was calculated as the percentage of participants with a confirmed CR or PR relative to the total number of participants enrolled. Response Evaluation Criteria in Solid Tumors (RECIST), version (v) 1.1 were used to define CR and PR. CR=disappearance of all preexisting lesions except nodal disease, with all nodal lesions decreased to normal size (short axis \<10 mm) and no appearance of new unequivocal malignant lesions. PR= ≥30% decrease from baseline of sum of diameters of all target lesions with no unequivocal progression of preexisting non-target lesions or appearance of new lesions. CR and PR were confirmed on a follow-up imaging assessment ≥4 weeks after the initial response documentation. ORR was analyzed only for participants with T790M mutation according to the primary study objective.

  From baseline to disease progression, up to 61 weeks.

Secondary Outcomes (7)

• Disease Control Rate (DCR) for Participants With T790M Mutation

  From baseline to baseline to disease progression, up to 61 weeks.

• Duration of Response in Participants With T790M Mutation

  From baseline to date of disease progression or death, up to 61 weeks.

• Progression-free Survival

  From baseline to disease progression or death, up to 61 weeks.

• Progression-free Survival at 4 Months

  Month 4

• Maximum Plasma Concentration (Cmax) for Dacomitinib and PF-05199265

  Pre-dose (hour 0), 2, 4, 6, 8, and 10 hours post-dose on Day 4, Cycle 0.

Study Arms (2)

Cohort A

EXPERIMENTAL

Patients with NSCLC whose tumor has a documented T790M mutation in exon 20 of the Epidermal Growth Factor Receptor.

Drug: Dacomitinib

Cohort B

EXPERIMENTAL

Patients with NSCLC. No requirement of a specific molecular signature, but excluding known T790M mutations.

Drug: Dacomitinib

Interventions

Dacomitinib DRUG

Dacomitinib 45 mg every 12 hours Days 1-4 of the first week, and then 60 mg every 12 hours Days 1-4 of each 2-week cycle thereafter. The dose of dacomitinib for patients in Cohort A may be further escalated in increments of 15 mg.

Cohort A

Eligibility Criteria

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

You may qualify if:

• Evidence of histologically confirmed, advanced NSCLC (stage IIIB/IV).
• Evidence of T790M mutation to enroll in Cohort A.
• Evidence of measurable disease by radiographic technique.
• Adequate organ function.

You may not qualify if:

• Patients with T790M mutation who stopped any prior EGFR-directed therapy without evidence of disease progression.
• Symptomatic brain metastases.
• Uncontrolled or significant cardiovascular disease.
• Pregnant or breastfeeding.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (14)

Tower Hematology Oncology Medical Group

Beverly Hills, California, 90211, United States

Location

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

Location

Georgetown University Hospital-Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Georgetown University Medical Center Department of Pharmacy, Research

Washington D.C., District of Columbia, 20007, United States

Location

Memorial Sloan-Kettering Cancer Center-Rockefeller Outpatient Pavilion

New York, New York, 10022, United States

Location

Investigational Drug Service, Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

UT Southwestern Medical Center-Simmons Cancer Center Pharmacy

Dallas, Texas, 75390-9015, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

UT Southwestern University Hospital - William P. Clements, Jr.

Dallas, Texas, 75390, United States

Location

UT Southwestern University Hospital - Zale Lipshy

Dallas, Texas, 75390, United States

Location

Severance Hospital, Yonsei University Health System

Seoul, 120-752, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Related Publications (2)

• Tan W, Giri N, Quinn S, Wilner K, Parivar K. Evaluation of the potential effect of dacomitinib, an EGFR tyrosine kinase inhibitor, on ECG parameters in patients with advanced non-small cell lung cancer. Invest New Drugs. 2020 Jun;38(3):874-884. doi: 10.1007/s10637-019-00887-0. Epub 2019 Dec 19.

  PMID: 31858327 DERIVED

• Yu HA, Ahn MJ, Cho BC, Gerber DE, Natale RB, Socinski MA, Giri N, Quinn S, Sbar E, Zhang H, Giaccone G. Phase 2 study of intermittent pulse dacomitinib in patients with advanced non-small cell lung cancers. Lung Cancer. 2017 Oct;112:195-199. doi: 10.1016/j.lungcan.2017.08.017. Epub 2017 Aug 23.

  PMID: 29191595 DERIVED

Related Links

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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

dacomitinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

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

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 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2013
• First Posted: May 21, 2013
• Study Start: July 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: July 18, 2017
• Results First Posted: July 18, 2017

Record last verified: 2017-07

Locations

KR (2); US (12)