Clinical trial NCT01912963
Conditions: HER2-positive Breast Cancer Metastatic Breast Cancer
Keywords: HER-2 Positive Breast Cancer Metastatic Breast Cancer
Sponsor: Dana-Farber Cancer Institute
Start date: 2013-09-01; Completion date: 2016-12-01
Enrollment: 32 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
In this study, the investigators are testing the effectiveness of the combination of eribulin, pertuzumab and trastuzumab to learn whether this combination of drugs works in treating advanced HER2-positive breast cancer that had received at least one prior treatment previously. At this point, the standard treatment for HER2-positive cancer that has progressed (grown) after a first treatment is chemotherapy combined with therapies that target the HER2 protein (e.g., trastuzumab or lapatinib).

Detailed description:
All of the medications that are being tested in this study are approved by the Food and Drug administration (FDA) for the treatment of metastatic breast cancer. However, the combination of these three medications in participants has not yet been tested. Eribulin is a chemotherapy agent that is approved for the treatment of metastatic breast cancer for women who have previously received at least two prior chemotherapeutic regimens for the treatment of their metastatic disease. Pertuzumab and trastuzumab are also both approved for the treatment of advanced HER2-positive breast cancer. Both agents help treat breast cancer by binding HER2 receptor. However, pertuzumab and trastuzumab bind to different parts of the HER2 receptor. Another scientific goal of this research study is to perform gene sequencing (gene tests) on your cancer cells (obtained from biopsies or surgery) and normal tissues (usually blood). The results of the gene tests will be used to try to develop better ways to treat and prevent cancers.

After the Phase I run-in, two cohorts based on prior exposure to pertuzumab were evaluated. The target accrual for Cohort A, without prior pertuzumab, is 56 participants. Using a two-stage design (n=34 stage 1, n=22 stage 2), there is 90% power assuming 10% Type I error to determine whether objective response (OR) rate is consistent with the alternative rate of 40% versus the null rate of 24%. There is 57% probability of stopping the trial at stage one if the true OR rate is 24%. Cohort B, with prior pertuzumab, is evaluated using a single stage design. There is 91% power to detect an improvement in OR from 10% to 30% with accrual of 25 participants.

Arms: arm 1: Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (D1)

Cycle duration=21 days

The Phase I run-in potentially evaluates 2 dose levels of eribulin in combination with pertuzumab and trastuzumab. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase. arm 2: Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase. arm 3: Pertuzumab: 840 mg/cycle 1 then 420 mg/cycle IV on day 1

Trastuzumab: 8 mg/kg/cycle 1 then 6 mg/kg cycle IV on day 1

Eribulin: 1.4 mg/m2/cycle IV on days 1 and 8 (recommended phase II dose)

Cycle duration=21 days

In the Phase II study, participants enrolled into two possible cohorts based on prior pertuzumab exposure. Participants first receive antibody administration then eribulin. In the treatment phase, participants receive up to 6 cycles of combination therapy unless disease progression (PD) or withdrawal for other reasons (w/d). Participants who complete 6 cycles have the option to continue with antibody therapy only until PD or w/d in the extension phase.
Interventions: intervention 1: Pertuzumab intervention 2: Trastuzumab intervention 3: eribulin
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol documents: