Clinical trial NCT00597038
Conditions: Metastatic Melanoma
Keywords: Dasatinib Dacarbazine
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Start date: 2007-11-01; Completion date: 2011-09-01
Enrollment: 50 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to:

Phase I Objectives:

* Find the most tolerated dose to use for Phase II
* Collect information on how the body responds to this combination of study drug

Phase II Objectives:

* To determine the overall response of participants using this combination of study drug

The expression of proto-oncogene tyrosine-protein kinase (Src), a substance present in a significant proportion of melanomas plays a role in the growth, multiplying, and dividing of cancer cells. Melanoma cells appear to be sensitive to these agents that block the action of Src in concentrations that can be achieved in patients. We suggest that Src inhibitors (such as Dasatinib) may be a good choice for treatment of melanoma in combination with Dacarbazine (a chemotherapy drug that can cause the shrinkage of melanomas). We wish to to evaluate the Src inhibitor Dasatinib in combination with the chemotherapy drug Dacarbazine. The novel oral Src inhibitor Dasatinib may be able to increase the effectiveness of chemotherapy for melanoma compared to chemotherapy alone. Dacarbazine is a standard treatment for melanoma currently. The effectiveness of this chemotherapy drug may be increased by combination with Dasatinib. Dacarbazine has been approved by the US Food and Drug Administration (FDA) for treating melanoma; Dasatinib has been approved by the FDA to treat leukemia, but it has not been approved alone or in combination with Dacarbazine to treat melanoma.

Detailed description:
Patient will receive Dacarbazine intravenously (IV), which means it is given through a needle in a vein in the arm or through a venous port (if patient already has one). Dasatinib will be given orally starting day 2 for 17 days straight (days 2 through 19) starting the day after patient receives their first dose of Dacarbazine. The therapy will be repeated every 21 days (21 days = 1 cycle). Patient may be given other drugs before each cycle to help reduce side effects of the therapy. If patient experiences severe side effects, the amount of Dacarbazine and/or Dasatinib they receive in future cycles may be decreased.

Cycle 1 day 1:

* Dacarbazine Intravenous
* Toxicity assessment - evaluation of any side effects that patient may be experiencing
* Medical history\*
* Physical examination\* - measure height, weight, blood pressure, pulse, breathing rate, temperature, assessment of patient's energy and activity level (Eastern Cooperative Group \[ECOG\] Performance Status)
* Blood tests (3 tablespoons) for safety tests\*- Complete blood count with differential and platelets (CBC), Comprehensive metabolic profile (CMP), \& Magnesium test \*(certain tests may not need to be performed if they were performed during screening within 1 week; study doctor will tell patient if they need to have these tests redone)

Cycle 1 day 8:

* Toxicity assessment - (these will be done for the first cycle of treatment, but will be discontinued for later cycles unless deemed necessary by study doctor)
* CBC - (1 tablespoon) (this will be done for the first cycle of treatment, but will be discontinued for later cycles unless deemed necessary by study doctor)
* Dasatinib orally

Cycle 1 day 15:

* Toxicity assessment - (these will be done for the first cycle of treatment, but will be discontinued for later cycles unless deemed necessary by study doctor)
* CBC - (1 tablespoon) these will be done for the first cycle of treatment, but will be discontinued for later cycles unless deemed necessary by study doctor)
* Dasatinib orally
* Blood sample for pharmacokinetic (PK) analysis

Patient will also take Dasatinib orally as instructed days: 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19 each cycle.

Day 1 for all cycles after the first cycle:

* Dacarbazine Intravenous (IV)
* Dasatinib orally
* Medical history
* Physical examination: measure height, weight, blood pressure, pulse, breathing rate, temperature, assessment of patient's energy and activity level (ECOG Performance Status)
* Blood tests (2 tablespoon) for safety tests: CMP \& CBC
* An electrocardiogram (EKG)
* Computed tomography (CT) scan (done every other cycle starting with cycle 2)
* Toxicity assessment

If patient decides not to continue participation in this study or is taken off the study by their study doctor or the sponsor they will return to the clinic for one more visit.

During this visit the following procedures will be performed:

* Medical history
* Perform a physical examination: measure height, weight, blood pressure, pulse, breathing rate, temperature, assessment of patient's energy and activity level (Eastern Cooperative Group \[ECOG\] Performance Status)
* Blood tests (2 tablespoons) for safety tests: CBC \& CMP
* Toxicity assessment Patient will need to take their assigned Dasatinib dose twice daily. It may be taken with or without food.

Arms: arm 1: Dasatinib and Dacarbazine (DTIC). The first cohort was a dasatinib dose of 50 mg by mouth (PO) twice a day (BID) given days 2-19 with DTIC given at a dose of 800 mg/m2 once every 3 weeks. The dose escalation was continued until MTD and a recommended Phase II dose was established. arm 2: Dasatinib and Dacarbazine (DTIC). The recommended phase II dose was dasatinib 70 mg BID with dacarbazine 800 mgm\^2.
Interventions: intervention 1: Dasatinib and Dacarbazine (DTIC)
Intervention descriptions: intervention 1: Arm A/ Phase I Potential Dose Levels.

Dose Level -1: Dasatinib 40 mg; DTIC 600 mg/m\^2. Dose Level 1: Dasatinib 50 mg; DTIC 800 mg/m\^2. Dose Level 2: Dasatinib 70 mg; DTIC 800 mg/m\^2. Dose Level 3: Dasatinib 70 mg; DTIC 1000 mg/m\^2.

Arm B/Phase II Potential Dose Levels.

MTD1: Dasatinib 70 mg; DTIC 1000 mg/m\^2. MTD2: Dasatinib 70 mg; DTIC 800 mg/m\^2. MTD3: Dasatinib 100 mg: DTIC 1000 mg/m\^2.

Protocol documents: