Decitabine in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This phase I trial is studying the side effects and best dose of decitabine in treating patients with advanced solid tumors that have not responded to previous treatment. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose of decitabine in patients with advanced solid tumors. II. Determine the toxic effects of this drug in these patients. III. Determine the dose of this drug with biologic activity in these patients. IV. Determine the pharmacokinetics of this drug in these patients. V. Determine clinical response to this drug in these patients. OUTLINE: This is a dose-escalation, multicenter study. Patients receive decitabine IV over 30 minutes on days 1-5 weekly for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of decitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed at 2 weeks.

Official Title
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A Phase I Study Of The Toxicities, Biologic And Clinical Effects Of Daily 5 Aza 2'Deoxycytidine (DAC), NSC 127716 (IND 50733) For Four Weeks In Patients With Advanced Malignancies

Conditions
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Male Breast Cancer, Recurrent Bladder Cancer, Recurrent Breast Cancer, Recurrent Melanoma, Stage III Melanoma, Stage IV Bladder Cancer, Stage IV Breast Cancer, Stage IV Melanoma, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: decitabine
* Other: pharmacological study
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of advanced metastatic solid tumor for which all standard therapy has failed, including, but not limited to the following: Stage III or IV melanoma Mucosal melanoma allowed No resectable stage III melanoma Bladder cancer Breast cancer No active symptomatic CNS disease No radiographically evident cerebral edema Hormone receptor status: Not specified Male or female Performance status - ECOG 0-1 Hemoglobin at least 9.0 g/dL Platelet count at least 100,000/mm^3 WBC at least 3,500/mm^3 Absolute granulocyte count at least 1,500/mm^3 No coagulation disorders Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT and SGPT less than 2.5 times ULN Hepatitis B surface antigen negative Hepatitis C antibody negative Creatinine no greater than 1.5 times ULN No major cardiovascular system illness No major respiratory system illness Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No major systemic infection At least 1 month since prior radiotherapy At least 1 month since any prior anticancer therapy or adjuvant therapy No other experimental treatment within 30 days prior to, during, and for 30 days after study therapy

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: Treatment (decitabine)<br>Patients receive decitabine IV over 30 minutes on days 1-5 weekly for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of decitabine until the MTD is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. | Drug: decitabine<br>* Given IV<br>* Other names: DAC;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose determined by dose-limiting toxicities graded according to CTC 2.0 toxicity criteria |  | 6 weeks |