Clinical trial NCT00924352
Conditions: Metastatic Breast Cancer
Keywords: Metastatic Breast Cancer
Sponsor: Accelerated Community Oncology Research Network
Start date: 2009-06-01; Completion date: 2013-10-01
Enrollment: 56 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The primary objective for the Phase I portion of the study is to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) and for the Phase II portion of the study is to evaluate progression free survival (PFS). Secondary objectives are response rate, clinical benefit rate, and overall toxicity.

Detailed description:
In the Phase I portion of the study, patients will receive study treatment according to the assigned dose level. Ixabepilone will be administered over 1 hour on Days 1, 8, and 15 of a 28-day cycle. Dasatinib will be administered continuously starting on Day 1, Cycle 1 once daily (QD).

Three patients will be enrolled at dose level 0 and observed for dose-limiting toxicity (DLT) for 1 course of treatment.

Dose escalation or reduction will depend on the number of patients experiencing DLT as follows:

* If 0 of 3 patients experiences a DLT, then 3 additional patients will be enrolled at the next higher dose level.
* If 1 of 3 patients experiences a DLT, then 3 additional patients will be enrolled at that dose level.
* If 2 of 3 or 3 of 3 patients experience a DLT, then 3 patients will be enrolled at the next lower dose unless 6 patients have already been treated at that dose.
* If ≥2 of 6 patients experience a DLT at that dose level, then the MTD is considered to have been exceeded. At that point, 3 patients are treated at the next lower dose.
* If no more than 1 of the 6 patients experiences a DLT, then the dose level will be escalated 1 level.

Maximum-tolerated dose (MTD) is defined as the dose at which ≤1 of 6 patients experience DLT, and above which ≥2 of 6 patients experience DLT.

In the Phase II portion of the study, dasatinib and ixabepilone will be administered at the MTD determined during Phase I. Dasatinib will be started on Day 1, Cycle 1 and will be administered continuously once daily. Ixabepilone will be administered over 1 hour on Days 1, 8, and 15 of a 28-day cycle. Patients will be treated with both agents for up to 8 cycles, after which stable or responding patients are eligible for monotherapy with dasatinib at the investigator's discretion in the absence of disease progression or unacceptable toxicity.

Arms: arm 1: Ixabepilone, for injection 15 mg supplied with diluent for ixabepilone, 8 mL. Dose Level 2;20 mg/m2,Dose Level 1;20 mg/m2,Dose Level 0 (Starting Dose);16 mg/m2,Dose Level - 1;12 mg/m2,Dose Level - 2;12 mg/m2.

Dasatinib tablets will be administered continuously starting on Day 1, Cycle 1 once daily (QD).Dose Level 2;140 mg QD,Dose Level 1;100 mg QD,Dose Level 0 (Starting Dose);100 mg QD,Dose Level - 1;100 mg QD,Dose Level - 2;70 mg QD.
Interventions: intervention 1: Dasatinib intervention 2: Ixabepilone
Intervention descriptions: intervention 1: Dasatinib tablets will be administered continuously starting on Day 1, Cycle 1 once daily (QD).Dose Level 2;140 mg QD,Dose Level 1;100 mg QD,Dose Level 0 (Starting Dose);100 mg QD,Dose Level - 1;100 mg QD,Dose Level - 2;70 mg QD. intervention 2: Ixabepilone, for injection 15 mg supplied with diluent for ixabepilone, 8 mL. Dose Level 2;20 mg/m2,Dose Level 1;20 mg/m2,Dose Level 0 (Starting Dose);16 mg/m2,Dose Level - 1;12 mg/m2,Dose Level - 2;12 mg/m2.

Protocol documents: