A Phase I-II Study of Dasatinib in Combination With Weekly Paclitaxel for Patients With Metastatic Breast Carcinoma
Overview
- Phase
- Phase 1
- Intervention
- Dasatinib and Paclitaxel
- Conditions
- Breast Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 55
- Locations
- 1
- Primary Endpoint
- Phase I Portion: Maximum Tolerated Dose/MTD of Dasatinib When Administered in Combination With a Fixed Dose of Weekly Paclitaxel.
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to find the highest dose of dasatinib that can be safely given to a patient when the drug is given in combination with the known anticancer drug paclitaxel. Paclitaxel is an established anti-cancer drug, used in the treatment of many cancers, and it is an approved treatment for breast cancer. Dasatinib has been approved by the Food and Drug Administration for use as a single therapy in another kind of cancer, but its use in breast cancer patients, and in combination with paclitaxel is investigational.
In this study, we will test the safety of dasatinib when given at different dose levels in combination with paclitaxel. We want to find out what effects, good and/or bad, it has on the patient and on metastatic breast cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female or male patients with diagnosis of invasive adenocarcinoma of the breast confirmed at MSKCC.
- •For the phase I portion, patients with any ER/PR/HER2 disease status, no longer eligible for hormonal therapy or HER2-targeted therapy, will be eligible.
- •For the phase II portion, there needs to be documentation of negative HER2 (IHC 0-1+ or FISH/CISH negative) status. Patients with any ER/PR disease status are eligible.
- •A paraffin-embedded tissue block or unstained slides from prior surgery must be available.
- •Evidence of recurrent or progressive locally advanced or metastatic breast cancer.
- •Presence of:
- •For the phase I portion: at least one evaluable or measurable metastatic lesion ,
- •For the phase II portion: at least one measurable metastatic lesion according to the RECIST criteria which has not been irradiated (i.e. newly arising lesions in previously irradiated areas are accepted). Ascites, pleural effusion, and bone metastases are not considered measurable. Minimum indicator lesion size: \> or = to 10 mm measured by spiral CT or \> or = to 20 mm measured by conventional techniques.
- •Prior therapies:
- •For the phase I portion: Any number of prior endocrine or biologic therapies is permitted . In addition, patients may be untreated in the metastatic setting or have received any number of prior cytotoxic regimens.
Exclusion Criteria
- •Life expectancy \< 3 months.
- •Prior severe allergic reaction to paclitaxel therapy.
- •Presence of new or recurrent pleural effusion which is symptomatic and/or requiring medical intervention (NCI CTC Grade 2, 3 or 4).
- •Completion of previous chemotherapy regimen \< 3 weeks prior to the start of study treatment.
- •Prior hormonal therapy must be discontinued prior to treatment start. Biologic therapy (eg, bevacizumab, trastuzumab) for the treatment of metastatic disease must be discontinued \> or = to 3 weeks from the start of protocol treatment.
- •Concurrent medical condition which may increase the risk of toxicity.
- •Patients may not have any clinically significant cardiovascular disease including the following:
- •myocardial infarction or ventricular tachyarrhythmia within 6 months
- •prolonged QTc \>480 msec (Fridericia correction)
- •ejection fraction less than institutional normal
Arms & Interventions
dasatinib and paclitaxel
The phase I portion is a standard, three-patient per cohort, dose escalation schedule will be used. Between 6 and 54 patients will likely be necessary to determine the MTD of dasatinib in combination with weekly paclitaxel. The phase II portion of this trial has a Simon two-stage design to determine the efficacy of dasatinib when administered in combination with paclitaxel.
Intervention: Dasatinib and Paclitaxel
Outcomes
Primary Outcomes
Phase I Portion: Maximum Tolerated Dose/MTD of Dasatinib When Administered in Combination With a Fixed Dose of Weekly Paclitaxel.
Time Frame: Through completion of Phase I, up to 1 year
Efficacy (Objective Response Rate; ORR; Complete Response (CR) + Partial Response (PR)) of Dasatinib When Administered in Combination With Weekly Paclitaxel at the MTD Established During the Phase I Portion of This Trial.
Time Frame: Through study completion, up to 2 years
Secondary Outcomes
- Participant Adverse Events to Measure Safety and Tolerability of Dasatinib When Administered in Combination With Weekly Paclitaxel.(Through study completion, up to 2 years)
- Median Time To Progression for Phase II Participants(Through study completion, up to 2 years)
- Median Overall Survival for Phase II Participants(Through study completion, up to 2 years)
- Median Progression Free Survival for Phase II Participants(Through study completion, up to 2 years)
- Phase II: Exploratory Somatic Gene Mutations Detection in Archived Tumor Samples(2 years)
- Phase II: Number of Participants With Clinical Benefit According to Circulating Tumor Cells (CTC) at Baseline and After 2 Cycles of Treatment (8 Weeks)(8 weeks)
- Phase II: Number of Participants With Clinical Benefit According to Tumor Biomarker Data: Assays of VEGFR2(8 weeks)