Conditions: Breast Cancer
Keywords: HKI-272 (NERATINIB) TEMSIROLIMUS (CCI-779) HER2-Amplified Triple-negative invasive adenocarcinoma 10-005 Nerlynx PB-272
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 99
Healthy volunteers: no

Brief 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.

Arms:
arm 1: This is an open-label, single arm, dose-escalation phase I-II 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. Patients with trastuzumab-refractory HER2-amplified disease or triple negative disease will be enrolled in both phases of this clinical trial.

Interventions: intervention 1: Temsirolimus intervention 2: Neratinib
Intervention descriptions: intervention 1: 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 intervention 2: 28 day treatment cycle

• 240 mg orally daily

Protocol document: