Back to resultsStudy Evaluating the Safety Of HKI-272 (Neratinib) In Subjects With Advanced Non-Small Cell Lung Cancer
Primary Purpose
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
HKI-272
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung focused on measuring Lung Cancer, HKI-272, Neratinib, Nerlynx
Eligibility Criteria
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.
Sites / Locations
- USC Norris Comprehensive Cancer Center
- Midwestern Regional Medical Center
- Massachusetts General Hospital, Yawkey Center for Outpatient Care
- University of Minnesota
- Memorial Sloan-Kettering
- Carolinas Hematology-Oncology Associates
- Case Western Reserve University
- Cleveland Clinic
- Vanderbilt University Medical Center
- Swedish Cancer Institute
- Seattle Cancer Care Alliance
- Institut Gustave Roussy
- Országos Korányi TBC és Pulmonológiai Intézet
- University of Debrecen
- Akademia Medyczna W Gdansku
- Mazowieckie Centrum Leczenia Chorób Płuc i Gruźlicy
- Wielkopolskie Centrum Chorób Płuc i Gruźlicy
- Dolnośląskie Centrum Chorób Płuc we Wrocławiu
- Hospital Germans Trias I Puyol
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Prior Tarceva or Iressa With EGFR Mutation
Prior Tarceva or Iressa w/o EGFR Mutation
No Prior EGFR Tyrosine Kinase Inhibitor Treatment
Arm Description
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
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
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)
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Full Information
NCT ID
NCT00266877
First Posted
December 16, 2005
Last Updated
April 6, 2018
Sponsor
Puma Biotechnology, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00266877
Brief Title
Study Evaluating the Safety Of HKI-272 (Neratinib) In Subjects With Advanced Non-Small Cell Lung Cancer
Official Title
A Phase 2 Study of HKI-272 In Subjects With Advanced Non-Small Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
December 2005 (Actual)
Primary Completion Date
January 2009 (Actual)
Study Completion Date
January 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Puma Biotechnology, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to learn whether HKI-272 is safe and effective in treating non-small cell lung cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
Keywords
Lung Cancer, HKI-272, Neratinib, Nerlynx
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
172 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Prior Tarceva or Iressa With EGFR Mutation
Arm Type
Experimental
Arm Description
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
Arm Title
Prior Tarceva or Iressa w/o EGFR Mutation
Arm Type
Experimental
Arm Description
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
Arm Title
No Prior EGFR Tyrosine Kinase Inhibitor Treatment
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
HKI-272
Other Intervention Name(s)
Neratinib
Intervention Description
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.
Primary Outcome Measure Information:
Title
Objective Response Rate for Neratinib in Patients With Non-small Cell Lung Cancer
Description
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.
Time Frame
From first dose date to progression/death or last tumor assessment, up to three years.
Secondary Outcome Measure Information:
Title
Clinical Benefit Rate for Neratinib in Patients With Non-small Cell Lung Cancer
Description
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.
Time Frame
From first dose date to progression/death or last tumor assessment, up to three years.
Title
Duration of Response for Neratinib in Patients With Non-small Cell Lung Cancer
Description
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.
Time Frame
From start date of response to first PD, assessed up to three years after the first randomization.
Title
Progression Free Survival for Neratinib in Patients With Non-small Cell Lung Cancer
Description
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.
Time Frame
From first dose date to progression/death, assessed up to three years.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Puma
Organizational Affiliation
Biotechnology
Official's Role
Study Director
Facility Information:
Facility Name
USC Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Midwestern Regional Medical Center
City
Zion
State/Province
Illinois
ZIP/Postal Code
60099
Country
United States
Facility Name
Massachusetts General Hospital, Yawkey Center for Outpatient Care
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Memorial Sloan-Kettering
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Carolinas Hematology-Oncology Associates
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-6868
Country
United States
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Országos Korányi TBC és Pulmonológiai Intézet
City
Budapest
ZIP/Postal Code
H-1529
Country
Hungary
Facility Name
University of Debrecen
City
Debrecen
ZIP/Postal Code
H-4012
Country
Hungary
Facility Name
Akademia Medyczna W Gdansku
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Mazowieckie Centrum Leczenia Chorób Płuc i Gruźlicy
City
Otwock
ZIP/Postal Code
05-400
Country
Poland
Facility Name
Wielkopolskie Centrum Chorób Płuc i Gruźlicy
City
Poznan
ZIP/Postal Code
60-569
Country
Poland
Facility Name
Dolnośląskie Centrum Chorób Płuc we Wrocławiu
City
Wrocław
ZIP/Postal Code
54-439
Country
Poland
Facility Name
Hospital Germans Trias I Puyol
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
12. IPD Sharing Statement
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Study Evaluating the Safety Of HKI-272 (Neratinib) In Subjects With Advanced Non-Small Cell Lung Cancer
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