Last updated on May 2019

A Dose-Escalation Study Evaluating the Combination of Trastuzumab Emtansine (T-DM1) With Neratinib in Women With Metastatic HER2-Positive Breast Cancer


Brief description of study

This study is being done for the following reasons:

  • The study has two parts. The purpose of the first part (Phase I) of the study is to find out the highest dose of neratinib that can be given safely with T-DM1.
  • The purpose of the second part of the study (Phase II) is to find out whether the dose of neratinib with T-DM1 determined in Phase I will keep breast cancer from getting worse for a period of time.
  • In order to learn more about study therapy levels in blood and discover genetic and protein changes associated with cancer, the study includes special research tests using samples from blood and from breast tumor. Blood samples will be collected before study treatment, once during treatment, and after study treatment stops.
  • In the optional part of this study, three biopsies will be performed to obtain fresh tumor samples from an area where your cancer has spread.

Detailed Study Description

The FB-10 study is designed as an open label, single arm, Phase Ib/II study with a dose-escalation phase and an expanded cohort (phase II) to evaluate the combination of trastuzumab emtansine (T-DM1) with neratinib in women with metastatic, HER2-positive breast cancer. The primary aim of the phase Ib portion of this study is to determine the safety and tolerability of the two-drug combination. The primary aim of the phase II portion is to demonstrate efficacy.

Patients will receive concurrent therapy with T-DM1 (3.6 mg/kg IV) on Day 1 of a 3-week (21 day) cycle and neratinib as a continuous daily oral dose. The neratinib dose-escalation will include 4 dose levels (120 mg, 160 mg, 200 mg, and 240 mg). At the recommended phase II dose (RP2D) of the T-DM1 and neratinib combination, up to 39 additional patients will be treated.

The sample size of the phase I portion of the study will be between 2 and 24 patients. The sample size of the Phase II portion will be 42 patients. Approximately 6 patients at the Phase I RP2D level will be included in the Phase II portion. The total study enrollment will be a maximum of 63 patients. Accrual is expected to occur over 16 months.

Submission of diagnostic tumor samples and blood samples for FB-10 correlative science studies will be a study requirement for all patients. Blood samples will be collected at baseline, at Cycle 2, Day 1, and at progression. Blood samples for pharmacokinetic (PK) determination will be collected at Phase 1 sites from consenting patients at various time points during the first 24 hours of study therapy (Cycle 1, Days 1 and 2).

An optional tumor biopsy will be procured from consenting patients from an accessible site of metastasis before study dose level assignment (after the patient has signed the consent form and has been screened for eligibility), after Cycle 1 of treatment, and at the time of disease progression.

Clinical Study Identifier: NCT02236000

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Women & Infants Hospital of Rhode Island

Providence, RI United States
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