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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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ClinicalTrials.gov Identifier: NCT00266877
Recruitment Status : Completed
First Posted : December 19, 2005
Results First Posted : April 13, 2018
Last Update Posted : April 13, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Lung Neoplasms Drug: HKI-272 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 172 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of HKI-272 In Subjects With Advanced Non-Small Cell Lung Cancer
Actual Study Start Date : December 2005
Actual Primary Completion Date : January 2009
Actual Study Completion Date : January 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Neratinib

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 Name: 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 Name: 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 Name: Neratinib




Primary Outcome Measures :
  1. Objective Response Rate for Neratinib in Patients With Non-small Cell Lung Cancer [ Time Frame: From 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 :
  1. Clinical Benefit Rate for Neratinib in Patients With Non-small Cell Lung Cancer [ Time Frame: From 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.

  2. Duration of Response for Neratinib in Patients With Non-small Cell Lung Cancer [ Time Frame: From 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.

  3. Progression Free Survival for Neratinib in Patients With Non-small Cell Lung Cancer [ Time Frame: From 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00266877


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

Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT00266877     History of Changes
Other Study ID Numbers: 3144A1-200
B1891037
First Posted: December 19, 2005    Key Record Dates
Results First Posted: April 13, 2018
Last Update Posted: April 13, 2018
Last Verified: April 2018

Keywords provided by Puma Biotechnology, Inc.:
Lung Cancer
HKI-272
Neratinib
Nerlynx

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Gefitinib
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action