Neratinib With and Without Temsirolimus for Patients With HER2 Activating Mutations in Non-Small Cell Lung Cancer
- Conditions
- HER2-mutant Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT01827267
- Lead Sponsor
- Puma Biotechnology, Inc.
- Brief Summary
This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter, multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus combination therapy in patients with non-small cell lung cancer (NSCLC) who have documented somatic HER2 mutations.
- Detailed Description
This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter, multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus combination therapy in patients with NSCLC and documented somatic HER2 mutations. Patients randomized at study entry into 1 of 2 treatment arms:
* Arm A: neratinib 240 mg orally once daily
* Arm B: neratinib 240 mg orally once daily plus temsirolimus 8 mg once weekly by intravenous (IV) infusion
In the case of disease progression, patients initially assigned to neratinib monotherapy arm given option to add temsirolimus 8 mg IV once weekly.
Patients on combination therapy given option to dose-escalate temsirolimus to 15 mg/week at the end of first cycle of treatment, if well tolerated and at the physician's discretion. If neratinib 240 mg/day plus temsirolimus 15 mg/week dose not well tolerated, patient subsequently dose reduced back to neratinib 240 mg/day plus temsirolimus 8 mg/week.
Dosing continuous on nominal 3-week cycles until evidence of progressive disease, unacceptable toxicity, or patient withdrawal of consent.
Disease measured radiographically at baseline and every 6 weeks until disease progression or withdrawal from the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 62
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description neratinib plus temsirolimus neratinib 240 mg neratinib plus 8 mg temsirolimus IV with optional dose escalation to 15 mg temsirolimus neratinib monotherapy neratinib 240 mg once daily with food, continuously in 21 day cycles neratinib plus temsirolimus temsirolimus 240 mg neratinib plus 8 mg temsirolimus IV with optional dose escalation to 15 mg temsirolimus
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included. ORR is defined as proportion of subjects who achieved confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
A complete or partial response must be confirmed no less than 4-weeks after the criteria for response are initially met.
- Secondary Outcome Measures
Name Time Method Clinical Benefit Rate (CBR) From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included. CBR is defined as the proportion of patients who achieved objective response (CR or PR) or stable disease (SD) for at least 12 weeks.
Progression Free Survival (PFS) From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included. Defined as time from date of randomization until the first disease recurrence or progression per RECIST V1.1 or death due to any cause; censored at the last assessable evaluation or at the initiation of new anti-cancer therapy. Disease assessment is based on investigator tumor assessments. If no post-baseline tumor assessment then censored at enrollment date.
Duration of Response (DOR) From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included. 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, progressive disease (PD), or death was objectively documented, taking as a reference for PD the smallest measurements recorded since enrollment, per RECIST (v1.1) criteria.
Overall Survival (OS) From randomization to death or end of long term follow-up, assessed up to 31.8 months. Defined as the time (month) from randomization to death due to any cause; censored at the date last known alive.
Trial Locations
- Locations (21)
Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Pittsburgh Cancer Institute
🇺🇸Pittsburgh, Pennsylvania, United States
Massachusettes General Hospital
🇺🇸Boston, Massachusetts, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
City of Hope
🇺🇸Duarte, California, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of California Los Angeles
🇺🇸Santa Monica, California, United States
CHU de Grenoble Hopital Albert Michallon
🇫🇷Grenoble, France
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Hopital Nord
🇫🇷Marseille, France
CHU de Toulous Hopital Larre
🇫🇷Toulouse, France
CHRU de Lille - Hopital Calmette
🇫🇷Lille, France
University of Colorado
🇺🇸Aurora, Colorado, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Hopitaux universitaires de Strasbourg Nouvel Hopital Civil
🇫🇷Strasbourg, France
Institut Gustave Roussy
🇫🇷Villejuif, France