Temozolomide Alone or With Pegylated Interferon-Alpha 2b (PGI) in Melanoma Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00525031
First received: August 31, 2007
Last updated: November 7, 2013
Last verified: November 2013
  Purpose

The goal of this clinical research study is to learn if temozolomide alone or given with pegylated interferon alpha-2b can help to control metastatic melanoma. Researchers also want to study the safety of these 2 treatments.

Objectives:

  1. To determine the anti-tumor activity (pathological response CR+PR) and toxicity of temozolomide (TMZ) alone or in combination with pegylated interferon alpha-2b (PGI) in patients with resectable stage IIIC or stage IV (M1a) metastatic melanoma prior to definitive surgical resection.
  2. To determine the relapse-free survival, overall survival and the impact of tumor response to chemotherapy in these patients.
  3. To differentiate the in vivo treatment effects of TMZ alone vs.TMZ plus PGI and correlate with clinical outcome by analysis the pre- and post-treatment tumors and peripheral blood mononuclear cells with respect to:

1) Known cellular and molecular markers of apoptosis and cell proliferation, 2) Promotor methylation status of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), 3) DNA sequence variability of tumor suppressor genes and DNA repair enzymes, 4) Tumor genomic expression profiles analysis by cDNA microarray and protein array


Condition Intervention Phase
Melanoma
Drug: Temozolomide (TMZ)
Drug: Pegylated Interferon Alpha-2b (PGI)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Randomized Phase II Neoadjuvant Study of Temozolomide Alone or With Pegylated Interferon-alpha 2b in Patients With Resectable AJCC Stage IIIB/IIIC or Stage IV (M1a) Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Pathological Response CR+PR [ Time Frame: Evaluated after a total of 8 weeks of therapy before definitive surgery. ] [ Designated as safety issue: No ]

Estimated Enrollment: 124
Study Start Date: August 2006
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Temozolomide (TMZ)
Temozolomide = TMZ - 150 mg/m^2 by mouth once daily for 7 days, followed by 7 days off (alternating weekly) for a total of 8 weeks.
Drug: Temozolomide (TMZ)
150 mg/m^2 by mouth once daily for 7 days, followed by 7 days off (alternating weekly) for a total of 8 weeks.
Other Name: Temodar
Experimental: Temozolomide (TMZ) + Pegylated Interferon-alpha 2b (PGI)

Temozolomide = TMZ and PGI = Pegylated Interferon-alpha 2b

Temozolomide 150 mg/m^2 by mouth once daily for 7 days, followed by 7 days off (alternating weekly) for a total of 8 weeks. Pegylated Interferon-alpha 2b 0.5 mcg/kg subcutaneous injection once weekly for a total of 8 weeks.

Drug: Temozolomide (TMZ)
150 mg/m^2 by mouth once daily for 7 days, followed by 7 days off (alternating weekly) for a total of 8 weeks.
Other Name: Temodar
Drug: Pegylated Interferon Alpha-2b (PGI)
0.5 mcg/kg subcutaneous injection once weekly for a total of 8 weeks.
Other Name: PEG-Intron

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically documented diagnosis of melanoma metastases.
  2. Stage IIIB/IIIC (N2b, N2c and N3) or stage IV (M1a) melanoma patients with measurable and potentially resectable metastases without clinical and radiological evidence of other distant metastases.
  3. An ECOG performance status of 0-1.
  4. Age 18 or older.
  5. Adequate organ function defined as follows: a.) Absolute granulocytes greater than or equal to 1,000/mm^3 and Platelets greater than or equal to 100,000/mm^3, b.) Serum bilirubin and serum creatinine of less than or equal to 1.5 times upper limit of laboratory normal. If serum creatinine is greater than 1.5 times upper limit of laboratory normal, the urine creatinine clearance must be greater than 60 ml/min., c.) SGOT (AST), SGPT (ALT) and alkaline phosphatase less than or equal to 3 times upper limit of laboratory normal.
  6. Patients have not had any previous systemic chemotherapy for metastatic melanoma. Prior biologic therapy, targeted therapy or immunotherapy are allowable, but must be at least 2 weeks since prior therapy before starting study drugs. No other concurrent chemotherapy, immunotherapy, or radiotherapy.
  7. Prior radiation therapy used to enhance local regional control is permitted, but must be at least 2 weeks since prior therapy before starting study drugs. In addition, the patient must have unirradiated metastatic sites for response evaluation and has fully recovered from its toxicity. Lesions within the prior field of radiation may only be used as indicator lesions if there has been recent evidence of disease progression after .
  8. Ability to understand and sign an informed consent form, indicating awareness of the investigational nature of this study.

Exclusion Criteria:

  1. Significant cardiac or pulmonary dysfunction, such as a history of severe cardiovascular disease, myocardial infarction within 6 months of the start of treatment, unstable angina, Class III or Class IV congestive heart failure, ventricular arrhythmia, or any uncontrolled arrhythmia.
  2. Current significant psychiatric illness.
  3. Serious infection requiring intravenous antibiotics, or any non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by complications of this therapy.
  4. Frequent vomiting or any medical condition (e.g. partial bowel obstruction) that could interfere with oral medication intake.
  5. Autoimmune or immunosuppressive disorders (e.g. HIV or AIDS-related illness).
  6. Patients who require therapy with systemic corticosteroids.
  7. No evidence of active secondary malignancy that requires chemotherapy within the past 2 years (excluding non-melanoma skin cancer, and/or all carcinoma in-situ)
  8. Pregnant or lactating women are ineligible. Women of childbearing potential must have a negative urine pregnancy test within a week of initiation of therapy. All patients must agree to use medically approved contraceptive measures to prevent pregnancy during treatment.
  9. Any other medical condition or reason that, in the principal investigator's opinion, makes the patient unsuitable to participate in a clinical trial.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00525031

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Schering-Plough
Investigators
Principal Investigator: Wen-Jen Hwu, MD PhD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00525031     History of Changes
Other Study ID Numbers: 2005-0143
Study First Received: August 31, 2007
Last Updated: November 7, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Melanoma
Temozolomide
Temodar
Pegylated Interferon Alpha-2b
PEG-Intron
PGI
Resectable metastatic melanoma
Surgery

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Interferon-alpha
Interferons
Peginterferon alfa-2b
Temozolomide
Dacarbazine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014