Decitabine in Treating Patients With Advanced Solid Tumors

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

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

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific; Recurrent Melanoma; Recurrent Bladder Cancer; Stage IV Bladder Cancer; Male Breast Cancer; Stage IV Breast Cancer; Stage IV Melanoma; Recurrent Breast Cancer; Stage III Melanoma
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: decitabine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033-0804
      • University of Southern California

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (decitabine); 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.

Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: decitabine; Given IV; Other Names: DAC; 5-aza-dCyd; 5AZA

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jeffrey Weber, University of Southern California

Study record dates

Study Major Dates

• Study Start: December 1, 2001
• Primary Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: February 14, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): February 7, 2013
• Last Update Submitted That Met QC Criteria: February 6, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Disease Attributes; Breast Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Breast Neoplasms; Recurrence; Urinary Bladder Neoplasms; Melanoma; Breast Neoplasms, Male; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine; Azacitidine
• Other Study ID Numbers: NCI-2012-02727; U01CA062505 (U.S. NIH Grant/Contract); OC-01-01; CDR0000069182 (Registry Identifier: PDQ (Physician Data Query))