Clinical trial NCT00715793: Combination of Decitabine and Temozolomide in the Treatment of Patients With Metastatic Melanoma
Official title: Phase I/II Trial of the Combination of Decitabine and Temozolomide in the Treatment of Patients With Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Malignant Melanoma
Keywords: Decitabine
Temozolomide
Metastatic
Melanoma
Non-resectable
Stage IIIB melanoma
stage IV melanoma
TMZ
DTIC
promoter methylation
skin cancer
chemotherapy
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Eisai Inc.
name: Schering-Plough
First posted: 2008-07-15
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Participants That Experienced a Dose Limiting Toxicity (DLT)
timeFrame: Up to 26 months
measure: Overall Response Rate (ORR)
timeFrame: Up to 30 months
measure: Recommended Phase 2 Dose (RP2D) of DAC + TMZ
timeFrame: Up to 26 months
Secondary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: Up to 30 months
measure: Progression-free Survival (PFS)
timeFrame: Up to 42 months
measure: 6-month Progression-free Survival (PFS) Rate
timeFrame: 6 months
measure: Overall Survival (OS)
timeFrame: Up to 42 months
measure: 1-year Overall Survival (OS) Rate
timeFrame: 12 months
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Hussein Tawbi, MD
role: PRINCIPAL_INVESTIGATOR
References: