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Study Evaluating the Safety Of HKI-272 (Neratinib) In Subjects With Advanced Non-Small Cell Lung Cancer

Phase 2
Completed
Conditions
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Interventions
Registration Number
NCT00266877
Lead Sponsor
Puma Biotechnology, Inc.
Brief Summary

The purpose of this study is to learn whether HKI-272 is safe and effective in treating non-small cell lung cancer.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
172
Inclusion Criteria
  • Pathologic diagnosis of NSCLC and current stage IIIB (with pleural effusion) or IV, not curable with conventional therapy. For Arm C, less than or equal to 20 pack-years smoking history and current non smoker. A pack year = number of packs of cigarettes smoked per day x years smoked.
  • Progression following at least 12 weeks of treatment with Tarceva or Iressa. (Arms A and B only)
  • ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2 (not declining within past 2 weeks).
  • Tumor sample available and adequate for analysis.
  • At least one measurable target lesion.
  • Adequate cardiac, kidney, and liver function
  • Adequate blood counts
Exclusion Criteria
  • More than 3 prior cytotoxic chemotherapy treatments for relapsed or metastatic disease.
  • Significant cardiac disease or dysfunction.
  • Prior treatment with anthracyclines with cumulative dose of >400 mg/m^2.
  • Active central nervous system metastases, as indicated by clinical symptoms and/or progressive growth.
  • Use of Tarceva or Iressa within 14 days of treatment day 1 (Arms A and B only).
  • Major surgery, chemotherapy, radiotherapy, investigational drugs, or other cancer therapy within 3 weeks of treatment day 1.
  • Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom.
  • Inability or unwillingness to swallow HKI-272 capsules.
  • Pregnant or breastfeeding women.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Prior Tarceva or Iressa With EGFR MutationHKI-272HKI-272 administered to patients whose disease has progressed following \> or = 12 weeks of treatment with Tarceva or Iressa and who have a tumor with an EGFR mutation demonstrated at screening
Prior Tarceva or Iressa w/o EGFR MutationHKI-272HKI-272 administered to patients whose disease has progressed following \> or = 12 weeks of treatment with Tarceva or Iressa and who have a tumor without an EGFR mutation demonstrated at screening
No Prior EGFR Tyrosine Kinase Inhibitor TreatmentHKI-272HKI-272 administered to patients with no prior EGFR tyrosine kinase inhibitor treatment, adenocarcinoma, \< or = 20 pack-year smoking history, and current non-smoker (no requirement for EGFR mutation)
Primary Outcome Measures
NameTimeMethod
Objective Response Rate for Neratinib in Patients With Non-small Cell Lung CancerFrom first dose date to progression/death or last tumor assessment, up to three years.

Objective response rate as reported by Independent Assessment (radiographic review by independent radiologists) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.

Secondary Outcome Measures
NameTimeMethod
Clinical Benefit Rate for Neratinib in Patients With Non-small Cell Lung CancerFrom first dose date to progression/death or last tumor assessment, up to three years.

Clinical benefit rate is the percentage of patients with Partial or Complete Response, or with Stable Disease \>= 12 Weeks per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Duration of Response for Neratinib in Patients With Non-small Cell Lung CancerFrom start date of response to first PD, assessed up to three years after the first randomization.

Measured from the time at which measurement criteria were first met for CR or PR (whichever status was recorded first), until the date of first recurrence, PD, or death was objectively documented, taking as a reference for PD the smallest measurements recorded since enrollment, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.

Progression Free Survival for Neratinib in Patients With Non-small Cell Lung CancerFrom first dose date to progression/death, assessed up to three years.

Defined as the interval from the date of randomization until the first date on which recurrence or progression, or death due to any cause, is documented, censored at the last assessable evaluation or at the initiation of new anticancer therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v 1.0 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Trial Locations

Locations (19)

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Case Western Reserve University

🇺🇸

Cleveland, Ohio, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

USC Norris Comprehensive Cancer Center

🇺🇸

Los Angeles, California, United States

Swedish Cancer Institute

🇺🇸

Seattle, Washington, United States

Institut Gustave Roussy

🇫🇷

Villejuif, France

Carolinas Hematology-Oncology Associates

🇺🇸

Charlotte, North Carolina, United States

Akademia Medyczna W Gdansku

🇵🇱

Gdansk, Poland

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Midwestern Regional Medical Center

🇺🇸

Zion, Illinois, United States

Massachusetts General Hospital, Yawkey Center for Outpatient Care

🇺🇸

Boston, Massachusetts, United States

Memorial Sloan-Kettering

🇺🇸

New York, New York, United States

Seattle Cancer Care Alliance

🇺🇸

Seattle, Washington, United States

Wielkopolskie Centrum Chorób Płuc i Gruźlicy

🇵🇱

Poznan, Poland

Országos Korányi TBC és Pulmonológiai Intézet

🇭🇺

Budapest, Hungary

University of Debrecen

🇭🇺

Debrecen, Hungary

Dolnośląskie Centrum Chorób Płuc we Wrocławiu

🇵🇱

Wrocław, Poland

Hospital Germans Trias I Puyol

🇪🇸

Badalona, Barcelona, Spain

Mazowieckie Centrum Leczenia Chorób Płuc i Gruźlicy

🇵🇱

Otwock, Poland

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