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

A Phase 2 Study of HKI-272 In Subjects With Advanced Non-Small Cell Lung Cancer

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

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung; Lung Neoplasms
• Intervention / Treatment: Drug: HKI-272

• Study Type: Interventional
• Enrollment (Actual): 172
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Hungary
  • Budapest, Hungary, H-1529
    • Orszagos Koranyi Tbc es Pulmonologiai Intezet
  • Debrecen, Hungary, H-4012
    • University of Debrecen
• Poland
  • Gdansk, Poland, 80-952
    • Akademia Medyczna W Gdansku
  • Otwock, Poland, 05-400
    • Mazowieckie Centrum Leczenia chorób Płuc i Gruźlicy
  • Poznan, Poland, 60-569
    • Wielkopolskie Centrum Chorób Płuc i Gruźlicy
  • Wrocław, Poland, 54-439
    • Dolnośląskie Centrum Chorób Płuc we Wrocławiu
• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias I Puyol
• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
  • Illinois
    • Zion, Illinois, United States, 60099
      • Midwestern Regional Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital, Yawkey Center for Outpatient Care
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Hematology-Oncology Associates
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6868
      • Vanderbilt University Medical Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prior Tarceva or Iressa With EGFR Mutation; HKI-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	Drug: HKI-272; 320mg or 240mg daily by mouth. The starting dose was reduced from 320mg to 240mg per amendment #1 to the protocol for subject safety and tolerability.; Other Names: Neratinib
Experimental: Prior Tarceva or Iressa w/o EGFR Mutation; HKI-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	Drug: HKI-272; 320mg or 240mg daily by mouth. The starting dose was reduced from 320mg to 240mg per amendment #1 to the protocol for subject safety and tolerability.; Other Names: Neratinib
Experimental: No Prior EGFR Tyrosine Kinase Inhibitor Treatment; HKI-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)	Drug: HKI-272; 320mg or 240mg daily by mouth. The starting dose was reduced from 320mg to 240mg per amendment #1 to the protocol for subject safety and tolerability.; Other Names: Neratinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate for Neratinib in Patients With Non-small Cell Lung Cancer	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.	From first dose date to progression/death or last tumor assessment, up to three years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate for Neratinib in Patients With Non-small Cell Lung Cancer	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.	From first dose date to progression/death or last tumor assessment, up to three years.
Duration of Response for Neratinib in Patients With Non-small Cell Lung Cancer	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.	From start date of response to first PD, assessed up to three years after the first randomization.
Progression Free Survival for Neratinib in Patients With Non-small Cell Lung Cancer	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.	From first dose date to progression/death, assessed up to three years.

Collaborators and Investigators

• Sponsor: Puma Biotechnology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2005
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: December 16, 2005
• First Submitted That Met QC Criteria: December 16, 2005
• First Posted (Estimate): December 19, 2005

Study Record Updates

• Last Update Posted (Actual): April 13, 2018
• Last Update Submitted That Met QC Criteria: April 6, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Lung Cancer; Neratinib; HKI-272; Nerlynx
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 3144A1-200; B1891037