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Melanotan-I

Afamelanotide, MT-I, [Nle4-D-Phe7]-α-MSH, Scenesse, CUV-1647

Quick Stats
Studies 225
Trials 100
Completed PHASE1, PHASE2 INTERVENTIONAL NCT00924352

Trial of Dasatinib Plus Ixabepilone in 2nd or 3rd Line Metastatic Breast Cancer

View on ClinicalTrials.gov Updated Dec 15, 2025

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.

Interventions

Name: Dasatinib
Type: DRUG
Description: 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.
Name: Ixabepilone
Type: DRUG
Description: 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.

Primary Outcomes

Measure: Determination of the Maximum Tolerated Dose (MTD) of Dasatinib When Given in Combination With Ixabepilone (Phase I)
TimeFrame: MTD was assessed during the first cycle of combination therapy (days 1-28).
Description: The MTD of dasatinib (taken daily, continuously) when given in combination with ixabepilone (administered on Days 1, 8, and 15 of a 28-day cycle) was determined using a standard 3 + 3 dose escalation cohort design. The total sample and the number of patients who receive each dose in this design depends on the frequency of dose limiting toxicities (DLT) at each dosage. The MTD was defined as the dose at which ≤ 1 of 6 patients experienced DLT, and above which ≥ 2 of 6 patients experienced DLT.
Measure: Determination of the Maximum Tolerated Dose (MTD) of Ixabepilone When Given in Combination With Dasatinib (Phase I)
TimeFrame: MTD was assessed during the first cycle of combination therapy (days 1-28).
Description: The MTD of ixabepilone (administered on Days 1, 8, and 15 of a 28-day cycle) when given in combination with dasatinib (taken daily, continuously) was determined using a standard 3 + 3 dose escalation cohort design. The total sample and the number of patients who receive each dose in this design depends on the frequency of dose limiting toxicities (DLT) at each dosage. The MTD was defined as the dose at which ≤ 1 of 6 patients experienced DLT, and above which ≥ 2 of 6 patients experienced DLT.
Measure: Determination of the Dose Limiting Toxicities (DLTs) of the Combination of Dasatinib and Ixabepilone (Phase I)
TimeFrame: DLTs were assessed during the first cycle of combination therapy (days 1-28).
Description: DLTs were assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose limiting toxicity was defined as any grade 4 hematologic event or any grade 3 or 4 non-hematologic event occurring during cycle 1 that is attributable to dasatinib, ixabepilone, or the combination. The following events were excluded from this definition: grade 4 neutropenia lasting for 3 days or less; grade 3 nausea responsive to antiemetics; grade 3 infection with normal ANC or grade 1 or 2 neutrophils; grade 3 diarrhea responsive to optimal use of antidiarrheal therapy.
Measure: Evaluation of Progression-free Survival (PFS) of the Combination of Dasatinib and Ixabepilone (Phase II)
TimeFrame: PFS was measured from day 1 of treatment until time of progression (assessed about every 8 weeks) or death, whichever came first, for up to 27.2 months.
Description: Disease progression was determined through radiology imaging measurements and by clinical or symptomatic progression during or after treatment. Progression is defined per RECIST v1.0 guidelines as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions.

Trial Information

NCT ID

NCT00924352

Status

Completed

Study Type

INTERVENTIONAL

Phases

PHASE1, PHASE2

Sponsor

Accelerated Community Oncology Research Network

Last Updated

December 15, 2025

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