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

NCT00820170 | Completed Phase 1 Results

• 1 other identifier: 08-122
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

Breast; Cancer; DASATINIB; TAXOL (PACLITAXEL); 08-122

Outcome Measures

Primary Outcomes (2)

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

  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.

  Through study completion, up to 2 years

Secondary Outcomes (7)

• Median Overall Survival for Phase II Participants

  Through study completion, up to 2 years

• 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 Progression Free Survival for Phase II Participants

  Through study completion, up to 2 years

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

  8 weeks

• Median Time To Progression for Phase II Participants

  Through study completion, up to 2 years

Study Arms (1)

dasatinib and paclitaxel

EXPERIMENTAL

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.

Drug: Dasatinib and Paclitaxel

Interventions

Dasatinib and Paclitaxel DRUG

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

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• For the phase II portion: 0-2 prior therapies for metastatic disease are allowed.
• Prior taxane therapy, either in the adjuvant or in the metastatic setting, either deliver weekly, q 2 weeks or q 3 weeks, will be permitted. Prior therapy with bevacizumab will be allowed. All previous chemotherapy, radiotherapy and intravenous biphosphonates must have been discontinued at least 3 weeks prior to study entry, 3 weeks also for trastuzumab and bevacizumab. All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to NCI CTC (Version 3) Grade ≤1.
• Endocrine therapy with an aromatase inhibitor, SERM (ie, tamoxifen) or fulvestrant is permitted, however it must be discontinued before enrolling in the study.
• ECOG performance status of 0 or 1.
• Age \> or = to 18 years old. Adequate Organ Function

You may not qualify if:

• Patient agrees to discontinue QT-prolonging agents strongly associated with Torsades de Pointes including: (patients must discontinue drug ≥ 7 days prior to starting dasatinib) such as:
• quinidine, procainamide, disopyramide
• amiodarone, sotalol, ibutilide, dofetilide
• erythromycin, clarithromycin
• chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
• cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
• The concomitant use of H2 blockers or proton pump inhibitors with dasatinib is not recommended. The use of antacids should be considered in place of H2 blockers or proton pump inhibitors in patients receiving dasatinib therapy. If antacid therapy is needed, the antacid dose should be administered at least 2 hours prior to or 2 hours after the dose of dasatinib.
• Patient may not be receiving any potent CYP3A4 inhibitors. These are prohibited (patients must discontinue drug ≥7 days prior to starting dasatinib) and include:
• itraconazole, ketoconazole, miconazole, coriconazole
• amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir
• ciprofloxacin, clarithromycin, diclofenac, doxycycline, enoxacin, imatinib, isoniazid
• ketamine, nefazodone, nicardipine, propofol, quinidine, telithromycin
• Women of childbearing potential (WOCBP) must have:
• A negative serum or urine pregnancy test within 72 hours prior to the start of study drug administration
• Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms

Interventions

Dasatinib; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Dr. Monica Fornier
• Organization: Memorial Sloan Kettering Cancer Center

fornierm@mskcc.org

646-888-4563

Study Officials

• Monica Fornier, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2009
• First Posted: January 12, 2009
• Study Start: January 1, 2009
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: August 13, 2019
• Results First Posted: August 13, 2019

Record last verified: 2018-08

Locations

US (1)