Metronomic Therapy in Patients With Metastatic Melanoma

Study Overview
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Brief Summary
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SUMMARY: Metronomic Therapy in Patients with Metastatic Melanoma: A Phase II Study of Low Dose Vinblastine, Cyclophosphamide, and Dacarbazine. Patients with measurable metastatic melanoma are eligible. All patients will be treated as outlined below with combined vinblastine, cyclophosphamide, and dacarbazine. Patients will be treated continuously, until evidence of progression of disease, or for up to two cycles following disappearance of all disease. A cycle will be defined as three weeks of continuous therapy with a one week rest.

Detailed Description
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Low dose continuous chemotherapy, called metronomic chemotherapy, is designed to target vascular cells and inhibit tumor growth and metastasises. A recent study in a melanoma mouse model has identified low dose vinblastine, cyclophosphamide and dacarbazine as a treatment which improves the animal's survival and is superior to full dose dacarbazine alone. This clinical trial seeks to translate this laboratory model directly into metastatic melanoma patients.

Official Title
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Metronomic Therapy in Patients With Metastatic Melanoma: A Phase II Study of Low Dose Vinblastine, Cyclophosphamide, and Dacarbazine

Conditions
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Metastatic Melanoma

Intervention / Treatment
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* Drug: vinblastine
* Drug: Cyclophosphamide
* Drug: dacarbazine


Participation Criteria
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Eligibility Criteria
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Metastatic melanoma with measurable disease Patients must be at least 4 weeks from their last immunotherapy, radiation, surgery or chemotherapy (6 weeks for nitrosoureas) and recovered from all ill Karnofsky Performance Status ≥60% Life expectancy ≥ twelve weeks Adequate end organ function Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study. Appropriate Contraception in both sexes The patient must be competent and signed informed consent. EXCLUSION CRITERIA Concomitant second malignancy except for non-melanoma skin cancer, and non-invasive cancer such as cervical CIS, superficial bladder cancer without local recurrence, breast CIS. In patients with a prior history of invasive malignancy, less than five years in complete remission. Have evidence of significant co-morbid illness such as uncontrolled diabetes - Uncontrolled brain metastasis: Patients with brain metastasis most have been treated with brain radiation therapy or surgery and remain clinically stable for a minimum of 4 weeks.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined Low Dose Treatment<br>A cycle of therapy is 3 weeks of continuous dosing with a 1 week rest. Schema of treatment is: 1 mg/m2 vinblastine three times a week iv 60 mg/m2 cyclophosphamide by mouth 15 mg/m2 dacarbazine three times a week iv | Drug: vinblastine<br>* 1 mg/m2 vinblastine given three times per week administered intravenously.<br>* Other names: Velban;Drug: Cyclophosphamide<br>* 60 mg/m2 cyclophosphamide taken orally every day for 3 weeks with one week rest<br>* Other names: Cytoxan;Drug: dacarbazine<br>* 15 mg/m2 dacarbazine given three times per week for 3 weeks with 1 week rest<br>* Other names: DTIC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Tumor evaluation will be performed every 8 weeks from day 1 of cycle 1 (+/- 1 week) while on therapy assessed by RECIST 1.0 criteria. | From date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response Rate | To be assigned a status of partial response or complete response, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met. In the case of stable disease, follow-up measurements must have met the stable disease criteria at least once after study entry at a minimum interval (in general, not less than 6-8 weeks) that is defined in the study protocol | Tumor evaluation will be performed every 8 weeks from day1 of cycle 1 (+ 1 week) while on therapy, clinical response will be assessed no less than 4 weeks after response criteria met. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metronomic Therapy, Metastatic Melanoma, Vinblastine, Cyclophosphamide, Dacarbazine