NCT01111825

Temsirolimus Plus Neratinib for Patients With Metastatic HER2-Amplified or Triple Negative Breast Cancer

A Phase I/II Trial of Temsirolimus Plus Neratinib for Patients With Metastatic HER2-Amplified or Triple Negative Breast Cancer

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 99 (actual)
• Sponsor: Puma Biotechnology, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, single arm, multi-center, multi-national, adaptive design, dose-escalation Phase 1/2 study to determine the maximum tolerated dose (MTD) of temsirolimus with daily neratinib, and to determine the safety and efficacy of this combination when given to patients with advanced breast carcinoma, specifically trastuzumab-refractory HER2-amplified disease or triple-negative disease.

Detailed description

Phase I Design A standard, 3+3, dose escalation schedule to determine the MTD of temsirolimus in combination with neratinib with no intrapatient dose escalation and a starting dose of temsirolimus 8 mg administered intravenously (IV) weekly (dose level 1) and three patients enrolled in each cohort. Phase II Design The phase II portion of this trial is comprised of three cohorts. Two of the cohorts utilized a Simon two-stage design to determine the sample size to assess the efficacy of temsirolimus when administered in combination with neratinib: HER2-amplified and triple negative breast cancer. The third cohort was a single stage design with HER2-amplified patients and dose escalation.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	Temsirolimus	28 day treatment cycle Phase 1 * Weekly intravenously (IV) on days 1, 8, 15, and 22 * Starting dose 8 mg IV weekly (dose level 1). Three patients initially enrolled in each cohort Phase 2 * Dose escalation cohort - 8 mg IV weekly on Days 1, 8, 15, and 22, and then 15 mg IV weekly starting on Day 29 * HER2-amplified and Triple negative - 8 mg IV weekly on Days 1, 8, 15, and 22
DRUG	Neratinib	28 day treatment cycle • 240 mg orally daily

Timeline

• Start date: 2010-04-01
• Primary completion: 2016-07-01
• Completion: 2016-07-01
• First posted: 2010-04-28
• Last updated: 2018-09-26
• Results posted: 2017-11-07

Locations

12 sites across 6 countries: United States, Denmark, France, Hong Kong, Spain, United Kingdom

Regulatory

• FDA-regulated drug study