Combination of Decitabine and Temozolomide in the Treatment of Patients With Metastatic Melanoma

NCT ID: NCT00715793

Last Updated: 2017-10-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2015-08-31

Brief Summary

The combination of TMZ and DAC may effect dual modulation of DNA repair genes resulting in improved clinical response.

Detailed Description

Primary Objectives:

• Phase I: To determine the safety, tolerability, and Phase II recommended dose of the combination of extended schedule TMZ and DAC.
• Phase II: To determine the efficacy, as measured by overall response rate, of the combination of extended schedule TMZ and DAC given at the Phase II recommended dose to patients with metastatic melanoma.

Secondary Objectives:

• To determine pharmacokinetics of the combination of TMZ and DAC in patients with metastatic melanoma.
• To determine, in peripheral blood mononuclear cells (PBMC) and tumor tissue, the pharmacodynamic effects of the combination of TMZ and DAC on promoter methylation and expression of selected genes and correlate these with response.
• To determine the progression-free survival of patients treated with the combination of TMZ and DAC.

Conditions

Malignant Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm

Group Type: EXPERIMENTAL

Decitabine

Intervention Type: DRUG

In Part I patients will be treated on a standard "3+3" phase I dose-escalation design starting at 0.075 mg/kg until a decitabine dose level of 0.15 mg/kg is reached, or, in case unacceptable toxicities are observed, at the maximum tolerated dose (Phase II recommended dose). Decitabine will be administered at the specified dose level, intravenously, daily 5 days a week for the first 2 weeks of a 6-week cycle.

Temozolomide

Intervention Type: DRUG

Temozolomide is available in 25 mg and 100 mg tablets that will be administered orally; doses will be rounded to the nearest 25 mg. Temozolomide will be administered orally at 75 mg/m2 daily for 4 weeks starting on week 2 of a 6-week cycle.

biopsy

Intervention Type: PROCEDURE

Fine needle aspirates (FNA) and/or core biopsies of tumor samples will be obtained from consenting patients with accessible, evaluable disease, on days 1, 8, 15, and 29 of the first cycle and when patients go off study. Biopsies are optional in Phase I and required for all consenting subjects in Phase II.

Interventions

Decitabine

In Part I patients will be treated on a standard "3+3" phase I dose-escalation design starting at 0.075 mg/kg until a decitabine dose level of 0.15 mg/kg is reached, or, in case unacceptable toxicities are observed, at the maximum tolerated dose (Phase II recommended dose). Decitabine will be administered at the specified dose level, intravenously, daily 5 days a week for the first 2 weeks of a 6-week cycle.

Intervention Type: DRUG

Temozolomide

Temozolomide is available in 25 mg and 100 mg tablets that will be administered orally; doses will be rounded to the nearest 25 mg. Temozolomide will be administered orally at 75 mg/m2 daily for 4 weeks starting on week 2 of a 6-week cycle.

Intervention Type: DRUG

biopsy

Fine needle aspirates (FNA) and/or core biopsies of tumor samples will be obtained from consenting patients with accessible, evaluable disease, on days 1, 8, 15, and 29 of the first cycle and when patients go off study. Biopsies are optional in Phase I and required for all consenting subjects in Phase II.

Intervention Type: PROCEDURE

Other Intervention Names

DTIC; TMZ; fine needle aspirate; FNA; core biopsy

Eligibility Criteria

Inclusion Criteria

• Patients who have non-resectable Stage IIIB or stage IV metastatic melanoma that have progressed despite prior therapies.
• Life expectancy of at least 12 weeks.
• ECOG performance status of 0, 1 and 2.
• ≥18 years of age.
• Patients who have not received any other chemotherapeutic, biological or investigational agent within 28 days of study drug administration.
• First line and active brain metastases (metastatic lesions to the brain that have been adequately treated with surgery and/or appropriate radiation therapy and that have documented stability for >4 weeks or >2 weeks if treated with stereotactic radiosurgery, remain eligible)

Exclusion Criteria

• Any evidence of renal dysfunction (proteinuria, estimated creatinine clearance from serum creatinine test of <60 ml/min).
• Impaired hepatic function (liver enzymes greater than twice the upper limit of normal or bilirubin > 2.0 except in patients with Gilbert's syndrome).
• Prior treatment with alkylating agents (including TMZ and DTIC).
• Active brain metastases (metastatic lesions to the brain that have been adequately treated with surgery and/or appropriate radiation therapy and that have documented stability for >4 weeks remain eligible).
• Active infections or serious general medical conditions.
• Female patients of child-bearing age who are not on adequate contraception, or are pregnant or breast-feeding.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: collaborator

Schering-Plough

INDUSTRY

Sponsor Role: collaborator

Hussein Tawbi

OTHER

Sponsor Role: lead

Responsible Party

Hussein Tawbi

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Hussein Tawbi, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

UPMC Cancer Centers

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

UPCI 07-008

Identifier Type: -

Identifier Source: org_study_id