Phase Ib/II Study of PLX 3397 and Eribulin in Patients With Metastatic Breast Cancer
The purpose of the Phase 1b portion of the study is to determine the best dose of PLX3397 when given in combination with standard dose eribulin (Halaven™). The purpose of the Phase 2 portion of the study is to find out what effects, good and/or bad, these drugs have on patients and their metastatic breast cancer.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Maximum tolerated dose of PLX3397 given in combination with with standard dose eribulin in patients with metastatic breast cancer (Phase 1b) [ Time Frame: Estimated up to 24 months ] [ Designated as safety issue: Yes ]
- Percentage of patients with chemotherapy pre-treated triple negative metastatic breast cancer treated with PLX3397 in combination with eribulin who are progression free at 12 weeks (Phase 2) [ Time Frame: Evaluated at week 12 tumor assessment ] [ Designated as safety issue: No ]
- Serum concentrations for the combination of PLX3397 and eribulin (Phase 1b) [ Time Frame: Up to 42 days. ] [ Designated as safety issue: No ]
- Safety of treatment (Phase 1b & 2) [ Time Frame: Approximately 24 months ] [ Designated as safety issue: Yes ]AE and toxicity assessments (laboratory tests, physical exams & history) on Days 1 and Day 8 of each cycle during treatment
- Immune response (Phase 1b & 2) [ Time Frame: Up to 42 days. ] [ Designated as safety issue: No ]
- Efficacy of drug combination including response rate and duration of response (Phase 2) [ Time Frame: Participants will be assessed every 3 weeks and have CT scans every 6 weeks during treatment. Average participation is approximately 24 months. ] [ Designated as safety issue: No ]
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||January 2016|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Experimental: Eribulin in combination with PLX3397
21 day treatment cycle: PLX3397 100-200 mg gelcaps, po daily & Eribulin 1.4 mg/m2 IV day 1 and 8
Lead in period of 5-7 d with PLX3397 at MTD po qd (day -7/5 to day 0)
21 day cycles; Day 1:
Dosage Form: 100 mg or 200 mg capsules, Dosage: 400 - 1000 mg, oral administrationDrug: Eribulin
Dosage Form: 1 mg per 2 mL (0.5 mg per mL); Solution (clear, colorless, sterile, packaged in glass vial) Dosage: 1.4 mg/m2, 2-5 min IV, Day 1, 8 q21 days
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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01596751
|Contact: Hope S. Rugo, MDemail@example.com|
|United States, California|
|UCSF Comprehensive Cancer Center||Recruiting|
|San Francisco, California, United States, 94115|
|Contact: Paula Fiermonte 415-885-7605 firstname.lastname@example.org|
|Contact: Lauren Metzroth 415-885-7213 Lauren.Metzroth@ucsfmedctr.org|
|Principal Investigator: Hope S. Rugo, MD|
|United States, North Carolina|
|Duke University Cancer Center||Not yet recruiting|
|Durham, North Carolina, United States, 27710|
|Contact: Kimberly Blackwell, MD 919-668-1748 email@example.com|
|Principal Investigator: Kimberly Blackwell, MD|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center||Not yet recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: Ingrid Mayer, MD 615-322-4967 Ingrid.firstname.lastname@example.org|
|Principal Investigator: Ingrid Mayer, MD|
|Study Chair:||Hope S. Rugo, MD||University of California, San Francisco|