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Trial record 41 of 42 for:    Malignant Hyperthermia 5

Combination of Decitabine and Temozolomide in the Treatment of Patients With Metastatic Melanoma (UPCI-07-008)

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ClinicalTrials.gov Identifier: NCT00715793
Recruitment Status : Completed
First Posted : July 15, 2008
Results First Posted : October 3, 2017
Last Update Posted : October 3, 2017
Sponsor:
Collaborators:
Eisai Inc.
Schering-Plough
Information provided by (Responsible Party):
Hussein Tawbi, University of Pittsburgh

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

Condition or disease Intervention/treatment Phase
Malignant Melanoma Drug: Decitabine Drug: Temozolomide Procedure: biopsy Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 39 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of the Combination of Decitabine and Temozolomide in the Treatment of Patients With Metastatic Melanoma
Study Start Date : June 2008
Actual Primary Completion Date : May 2015
Actual Study Completion Date : August 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Single Arm Drug: 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.
Other Name: DTIC

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.
Other Name: TMZ

Procedure: 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.
Other Names:
  • fine needle aspirate
  • FNA
  • core biopsy




Primary Outcome Measures :
  1. Percentage of Participants That Experienced a Dose Limiting Toxicity (DLT) [ Time Frame: Up to 26 months ]
    Dose-limiting toxicities (DLTs) were defined as grade 4 neutropenia or thrombocytopenia which lasts >7 days; grade 3 or 4 febrile neutropenia; grade 3 or greater non-hematological toxic effects.

  2. Overall Response Rate (ORR) [ Time Frame: Up to 30 months ]
    Using RECIST v1.0 criteria, overall response rate (ORR) was determined by the number of participants with complete response (CR) + the number of participants with partial response (PR) / the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) + the number of participants with progressive disease (PD), multiplied by 100. Per RECIST v1.0 criteria (assessed by MRI or CT): Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response (PR) nor sufficient increase to to qualify for Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions.

  3. Recommended Phase 2 Dose (RP2D) of DAC + TMZ [ Time Frame: Up to 26 months ]
    Toxicity assessments used CTCAE v3.0. Two dose levels were explored in the phase I portion of the study. A modified 3 + 3 'up and down' design was used. Given the knowledge that DAC exhibits its epigenetic effects at 30-fold lower doses than at its maximum-tolerated dose (MTD), escalation of DAC to the MTD was not done.


Secondary Outcome Measures :
  1. Disease Control Rate (DCR) [ Time Frame: Up to 30 months ]
    Using RECIST v1.0 criteria, disease control rate (DCR) was determined by the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) / the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) + the number of participants with progressive disease (PD). Per RECIST v1.0 criteria (assessed by MRI or CT): Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response (PR) nor sufficient increase to to qualify for Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions.

  2. Progression-free Survival (PFS) [ Time Frame: Up to 42 months ]
    PFS was defined as the time from study entry until the documented radiological or symptomatic progression. Per RECIST v1.0 criteria (assessed by MRI or CT): Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions.

  3. 6-month Progression-free Survival (PFS) Rate [ Time Frame: 6 months ]
  4. Overall Survival (OS) [ Time Frame: Up to 42 months ]
    OS was defined as the time from study entry until the death or date of last contract.

  5. 1-year Overall Survival (OS) Rate [ Time Frame: 12 months ]
    Percentage of patients alive at one year (number of patients alive / total number of evaluable (analyzed) patients).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00715793


Locations
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United States, Pennsylvania
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Hussein Tawbi
Eisai Inc.
Schering-Plough
Investigators
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Principal Investigator: Hussein Tawbi, MD University of Pittsburgh

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Responsible Party: Hussein Tawbi, Principal Investigator, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00715793     History of Changes
Other Study ID Numbers: UPCI 07-008
First Posted: July 15, 2008    Key Record Dates
Results First Posted: October 3, 2017
Last Update Posted: October 3, 2017
Last Verified: September 2017
Keywords provided by Hussein Tawbi, University of Pittsburgh:
Decitabine
Temozolomide
Metastatic
Melanoma
Non-resectable
Stage IIIB melanoma
stage IV melanoma
TMZ
DTIC
promoter methylation
skin cancer
chemotherapy
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Temozolomide
Decitabine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Enzyme Inhibitors