Carboplatin, Paclitaxel, and Temozolomide for Patients With Metastatic Melanoma

Study Overview
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Brief Summary
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The number of melanoma cases has been steadily increasing over the past few decades. For many patients with metastatic melanoma, there are no effective therapies. The goal of this study is to determine whether a combination drug treatment of carboplatin, paclitaxel and temozolomide is effective in the treatment of metastatic or recurrent melanoma.

Detailed Description
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Over the past several decades, significant research has been conducted to try to identify active chemotherapeutic agents for the treatment of melanoma. The rationale for combining taxanes and platinum agents is that both have activity in melanoma; in vitro and clinical data suggest synergy between these drugs when used in combination in a wide variety of tumors, including melanoma; and the toxicity profiles of these agents do not overlap. Temozolomide (a drug approved for the treatment of melanoma) has been combined with other drugs, including taxanes and platinums, in previous clinical trials for melanoma. Specifically, a previous phase I study of the combination of temozolomide, paclitaxel, and carboplatin in melanoma showed objective responses. The efficacy of this combination is now being studied in this phase II trial.

Official Title
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Phase II Trial of Carboplatin, Paclitaxel, and Temozolomide for Patients With Metastatic Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Paclitaxel, carboplatin, temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients with biopsy proven advanced melanoma are eligible if there is measurable disease. Patients must have a life expectancy of at least 12 weeks. Prior surgery, immunotherapy, minimal chemotherapy (1 drug for less than 4 months), or radiotherapy for primary tumor is acceptable but must be completed at least 4 weeks from study entry, and patient should have completely recovered from such procedures. Patients must have a Zubrod performance status of 0-2. Patients must sign an informed consent. Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of ≥ 1500 cells/mm3, hemoglobin > 8 g/dl, platelet count ≥ 100 000/mm3. Patients should have a normal hepatic function with a total bilirubin < 1.5 the upper limit of normal (ULN) and serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase (SGPT) < 2 times the upper limit of normal (ULN),and adequate renal function as defined by a serum creatinine ≤ 1.5 times the ULN. Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and at least for 3 months. Patients with brain metastases are eligible if they have been appropriately treated, are asymptomatic Exclusion Criteria: Pregnant women or nursing mothers are not eligible. Patients must not receive any other concurrent chemotherapy or radiation during this trial. Patients with severe medical problems that would interfere with the therapy are not eligible.

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: Chemotherapy Combination<br>Chemotherapy Combination of paclitaxel, carboplatin, temozolomide: Carboplatin at an AUC of 5 on Day 1, paclitaxel at 175 mg/m2 on Day 1, and temozolomide at 125 mg/m2 Day 2-Day 6, on a 28 day cycle. | Drug: Paclitaxel, carboplatin, temozolomide<br>* Combination chemotherapy was administered for up to 6 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by physical exam and/or computerized tomography (CT): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The Objective Response Rate (ORR) is the sum of the percentages of patients achieving CR or PR. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The time from treatment initiation to death by any cause. | 2 years | 
| Safety Profile | All toxicities encountered during the study by patients who receive at least one on-study treatment will be graded according to the NCI CTCAE (Version 3.0). The number of patients experiencing adverse events will be reported according to grade. | Up to 30 days after last on-study treatment, for up to 2 years | 
| Time to Progression | The time from treatment initiation to disease progression or death by any cause. Progression is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by physical exam or computerized tomography (CT): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic, melanoma, skin cancer, paclitaxel, carboplatin, temozolomide