Enhancing Efficacy of Chemotherapy in Triple Negative/Basal-Like Breast Cancer by Targeting Macrophages: A Multicenter Phase Ib/II Study of PLX 3397 and Eribulin in Patients With Metastatic Breast Cancer
This is a nonrandomized, open label phase Ib/II study evaluating the safety and efficacy of
eribulin in combination with PLX3397, a novel CSF1 inhibitor, in patients with metastatic
breast cancer. The phase II portion of this trial will be limited to patients with triple
negative disease.
The phase I portion of this trial is a dose escalation of PLX3397 to determine the maximum
tolerated dose (MTD) of PLX3397 when given in combination with standard dose eribulin.
Patients will be enrolled in cohorts of three, using the dose levels and plan outlined in
the statistical section, with 6 patients enrolled at the MTD. All patients with accessible
tumor will be required to have a tumor biopsy at study start before starting therapy.
Pharmacokinetics of PLX3397 and eribulin, and blood levels of CSF1 will be obtained as
outlined in section 14. To allow rapid accrual to phase Ib, and an earlier start to the
phase II trial, patients will be enrolled in phase I with both hormone receptor positive and
negative disease, and at any line of therapy assuming eligibility criteria are otherwise
met.
Dose limiting toxicity (DLT) will be defined as any treatment-related toxicity meeting the
criteria below and occurring within the first 21 days of combination therapy. Patients must
receive at least 14 days of PLX3397 and 2 doses of eribulin during the first cycle in order
to be considered evaluable for DLT (unless the missed doses are due to a DLT).
Patients in each cohort will be followed for at least 3 weeks (one full cycle) before
opening accrual to the next dose level. If one patient in any cohort develops a DLT, an
additional 3 patients will be enrolled at that level. If no additional toxicities occur in
the six patients, then this particular dose would be used for the phase II trial, and the
next higher dose would be considered the MTD. A minimum of 12 and maximum of 24 patients
will be enrolled in the phase I study. The phase II trial will not open until the last
patient in the phase I study has been followed for at least 3 weeks.
The phase II portion of this trial will evaluate PFS in patients with TNBC treated with
PLX3397 and eribulin, using the dose of PLX3397 determined in the phase Ib study in a
two-step design. Please see the statistical section for details regarding enrollment and
statistical design. Treatment is preceded by a 5 to 7 day lead-in phase, in which patients
will take PLX3397 alone daily. Patients with accessible tumor will undergo a core biopsy of
tumor before the start of PLX3397 treatment, and then a fine needle aspiration or core
biopsy will be performed on the day of or the day before the start of eribulin (day -1 to
day 0).
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of PLX3397 given in combination with with standard dose eribulin in patients with metastatic breast cancer (Phase 1b)
Estimated up to 24 months
Yes
Hope S. Rugo, MD
Study Chair
University of California, San Francisco
United States: Food and Drug Administration
UCSF Protocol No. 12751
NCT01596751
July 2012
January 2016
Name | Location |
---|---|
Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
UCSF Comprehensive Cancer Center | San Francisco, California 94115 |
Duke University Cancer Center | Durham, North Carolina 27710 |