Safety Study of Dacarbazine and Bortezomib in Melanoma and Soft Tissue Sarcoma

Study Overview
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Brief Summary
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Bortezomib will enhance the activity of dacarbazine against melanoma and soft tissue sarcoma. Weekly administration of the combination will prove to be feasible and tolerable at an appropriate dose.

Detailed Description
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The primary objective is to determine recommended phase II doses for the combination dacarbazine and bortezomib administered weekly. Secondary objectives are to determine the maximum tolerated dose combination and to observe anti-tumor activity in terms of response rate(s), duration of response, time to progression, and time on treatment (a measure of both antitumor activity and treatment tolerance).

Official Title
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Phase I Trial of Dacarbazine and Bortezomib in Melanoma and Soft Tissue Sarcoma

Conditions
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Melanoma, Soft Tissue Sarcoma, Parathyroid Carcinoma, Small Cell Carcinoma of the Lung, Carcinoid Tumors

Intervention / Treatment
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* Drug: Dacarbazine and bortezomib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic diagnosis of cutaneous or mucosal melanoma, soft tissue sarcoma (STS), or an APUD (amine precursor uptake and decarboxylation) tumor. APUD tumors include parathyroid carcinoma, medullary carcinoma of the thyroid, small cell carcinoma of the lung, pheochromocytoma, islet cell tumors, carcinoid tumors, and malignant paraganglioma. Measurable or evaluable disease not appropriate for resection and/or radiation with curative intent. Patients with small cell carcinoma must have extended stage disease or, if limited stage disease, must have received at least one prior systemic therapy. Age 18 years or greater ECOG Performance Status 0 or 1 Women must be post-menopausal, infertile as the result of a surgical procedure, or willing to use a medically accepted form of birth control (abstinence, hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condon with spermicide) for the duration of study treatment. Men also must agree to use a medically accepted form of birth control for the duration of study treatment. Exclusion Criteria: Uncontrolled brain metastatic disease Platelet count <100 Absolute neutrophil count <1.5 Blood transfusion or hematopoietic growth factors for cytopenia within one month of enrollment. Calculated or measured (Cockcroft and Gault formula) creatinine clearance <30 mL/minute AST > 3 times the upper limit of normal, unless elevation due to metastatic disease, in which case AST > 5 times the upper limit of normal Bilirubin > 2 mg/mL Grade 2 or greater peripheral neuropathy Hypersensitivity to bortezomib, boron, mannitol, or dacarbazine Pregnant or nursing Other investigational drugs within 14 days of enrollment Other medical or other condition(s) that in the opinion of the investigator/sub-investigator might compromise the objectives of the study

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: A<br>dacarbazine + bortezomib | Drug: Dacarbazine and bortezomib<br>* Level 0: Dacarbazine 190 mg/m2 + Bortezomib 1.0 mg/m2; Level 1: Dacarbazine 250 mg/m2 + Bortezomib 1.0 mg/m2; Level 2: Dacarbazine 250 mg/m2 + Bortezomib 1.3 mg/m2; Level 3: Dacarbazine 250 mg/m2 + Bortezomib 1.6 mg/m2; Level 4: Dacarbazine 330 mg/m2 + Bortezomib 1.6 mg/m2; Level 5: Dacarbazine 440 mg/m2 + Bortezomib 1.6 mg/m2; Level 6: Dacarbazine 580 mg/m2 + Bortezomib 1.6 mg/m2<br>* Other names: bortezomib (velcade);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as measured by serious adverse events |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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melanoma, soft tissue sarcoma, APUD tumor, dacarbazine, bortezomib, velcade