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

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00266877
• Other study ID #: 3144A1-200
• Secondary ID: B1891037
• Status: Completed
• Phase: Phase 2
• First received: December 16, 2005
• Last updated: April 6, 2018
• Start date: December 2005
• Est. completion date: January 2009

Study information

• Verified date: April 2018
• Source: Puma Biotechnology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 172
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

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.

Locations

Country	Name	City	State
France	Institut Gustave Roussy	Villejuif
Hungary	Országos Korányi TBC és Pulmonológiai Intézet	Budapest
Hungary	University of Debrecen	Debrecen
Poland	Akademia Medyczna W Gdansku	Gdansk
Poland	Mazowieckie Centrum Leczenia Chorób Pluc i Gruzlicy	Otwock
Poland	Wielkopolskie Centrum Chorób Pluc i Gruzlicy	Poznan
Poland	Dolnoslaskie Centrum Chorób Pluc we Wroclawiu	Wroclaw
Spain	Hospital Germans Trias I Puyol	Badalona	Barcelona
United States	Massachusetts General Hospital, Yawkey Center for Outpatient Care	Boston	Massachusetts
United States	Carolinas Hematology-Oncology Associates	Charlotte	North Carolina
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Memorial Sloan-Kettering	New York	New York
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	Midwestern Regional Medical Center	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Puma Biotechnology, Inc.

Countries where clinical trial is conducted

United States,  France,  Hungary,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.