Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Paclitaxel

Albumin-Bound Paclitaxel

Dasatinib

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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.

A treatment cycle will consist of 28 days, according to the following schedule:

Dasatinib 120MG PO once daily, Weekly paclitaxel 80 mg/m2 given intravenously over 1 hour on day 1, 8, and 15 of a 28 day cycle.

The trial will initially test the combination of weekly paclitaxel and dasatinib given PO, once daily , continuously. In case of 2 dose-limiting toxicities (DLT) in the first cohort (0), the next cohort will test dasatinib given with a different schedule, 5 days on and 2 days off, omitting dasatinib the day prior and the day of administration of paclitaxel.

Dasatinib and Paclitaxel

Monica Fornier, MD

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.

Dasatinib In Combination With Weekly Paclitaxel For Patients With Metastatic Breast Carcinoma CA 180 194

A Phase I-II Study of Dasatinib in Combination With Weekly Paclitaxel for Patients With Metastatic Breast Carcinoma

Overall Survival for Phase II Participants

Per RECIST criteria, Progression (PD) is defined at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Tumor biomarker data obtained at baseline and after 2 cycles of treatment (8 weeks), will be performed by enzyme-linked immunosorbent assay. Clinical Benefit is defined as the sum of the percentage of participants who achieved CR, PR and stable disease for \> 6 months.

Bristol-Myers Squibb

Memorial Sloan Kettering Cancer Center

3 participants treated in the Phase I portion of the study at Paclitaxel 80mg/m2 + Dasatinib 120 mg were included in the group of 40 participants in the Phase II portion of this study.

Paclitaxel 80 mg/m2 weekly 3/4; Dasatinib 100 mg daily continuously

Phase 1: Paclitaxel 80 mg/m2 + Dasatinib 100 mg

Paclitaxel 80 mg/m2 weekly 3/4; Dasatinib 150 mg daily continuously

Phase 1: Paclitaxel 80 mg/m2 + Dasatinib 150 mg

Paclitaxel 80 mg/m2 weekly 3/4; Dasatinib 70 mg daily continuously

Phast 1: Paclitaxel 80 mg/m2 + Dasatinib 70 mg

Paclitaxel 80 mg/m2 weekly 3/4; Dasatinib 120 mg daily continuously

Phase 2: Paclitaxel 80 mg/m2 + Dasatinib 120 mg

No Arm Selected

Phase 1: Paclitaxel 80 mg/m2 + Dasatinib 70 mg

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

The 3 participants treated in the Phase I portion of the study at Paclitaxel 80mg/m2 + Dasatinib 120 mg were included in the group of 40 participants in the Phase II portion of this study.

Dr. Monica Fornier

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.

Dasatinib and Paclitaxel: A treatment cycle will consist of 28 days, according to the following schedule:

Dasatinib 120MG PO once daily, Weekly paclitaxel 80 mg/m2 given intravenously over 1 hour on day 1, 8, and 15 of a 28 day cycle.

The trial will initially test the combination of weekly paclitaxel and dasatinib given PO, once daily , continuously. In case of 2 dose-limiting toxicities (DLT) in the first cohort (0), the next cohort will test dasatinib given with a different schedule, 5 days on and 2 days off, omitting dasatinib the day prior and the day of administration of paclitaxel.

15 participants were enrolled for the Phase I portion of the study. These 15 participants determined the MTD for the study.

Phase I Portion: Maximum Tolerated Dose/MTD of Dasatinib When Administered in Combination With a Fixed Dose of Weekly Paclitaxel.

The 3 participants treated in the Phase I portion of the study at Paclitaxel 80mg/m2 + Dasatinib 120 mg were included in the group of 40 participants in the Phase II portion of this study. Results and data analysis reflect this.

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.

This objective is specific for the Phase II participants

Median Overall Survival for Phase II Participants

Arm 1: Paclitaxel 80 mg/m2 + Dasatinib 100 mg

Arm 2: Paclitaxel 80 mg/m2 + Dasatinib 120 mg

Arm 3: Paclitaxel 80 mg/m2 + Dasatinib 150 mg

Paclitaxel 80 mg/m2 + Dasatinib 70 mg

Participant Adverse Events to Measure Safety and Tolerability of Dasatinib When Administered in Combination With Weekly Paclitaxel.

Median Progression Free Survival for Phase II Participants

Phase II: Number of Participants With Clinical Benefit According to Tumor Biomarker Data: Assays of VEGFR2

Median Time To Progression for Phase II Participants

Phase II: Number of Participants With Clinical Benefit According to Circulating Tumor Cells (CTC) at Baseline and After 2 Cycles of Treatment (8 Weeks)

Spots Global Cancer Trial Database for Dasatinib In Combination With Weekly Paclitaxel For Patients With Metastatic Breast Carcinoma CA 180 194

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