Clinical trial NCT00525031
Conditions: Melanoma
Keywords: Melanoma Temozolomide Temodar Pegylated Interferon Alpha-2b PEG-Intron PGI Resectable metastatic melanoma Surgery
Sponsor: M.D. Anderson Cancer Center
Start date: 2006-08-01; Completion date: 2016-06-01
Enrollment: 55 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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 complementary DNA (cDNA) microarray and protein array

Detailed description:
Temozolomide is a drug that is designed to work by stopping cancer cells from making new DNA. If they cannot make DNA, they can't split into 2 new cancer cells.

Pegylated Interferon alpha-2b is a protein made by the human immune system that helps to fight viral infections and regulate cell function.

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of two treatment groups (Arm A or Arm B). You have an equal chance of being assigned to either group and getting the treatment assigned to that group. You will not know which group you are assigned to.

Arm A: Participants in this group will take temozolomide once a day for 7 days in a row. This will be followed by 7 days without any treatment. This will be repeated 3 more times(for a total of 8 weeks - 1 cycle) before you have routine surgery.

Arm B: Participants in this group will take temozolomide on the same schedule as those in Arm A. However, participants in this group will also receive pegylated interferon alpha-2b as an injection under the skin once a week for a total of 8 weeks before they have routine surgery. Tylenol will be given to participants in this group before their pegylated interferon alpha-2b injection. After the first injection, they will also need to stay in the clinic for 2 hours of observation.

Your body weight will be used when calculating the dosage of Temozolomide.

You will have blood (about 1 tablespoon each time) drawn at 2 times, to check your response to treatment. The first sample will be drawn before you start treatment. The second sample will be drawn around Day 57 of treatment.

On Days 15, 29, 43, and 57 of treatment, you will be asked about any illness you have experienced and any medications you may be taking. You will have a physical exam, including measurement of vital signs. You will have tumor measurements and a performance status evaluation. You will also have about 1 tablespoon of blood drawn for routine tests at each visit . Any side effects you may have experienced will also be recorded.

All participants will receive 1 cycle (8 weeks) of treatment followed by surgery to remove the tumor. The size of the tumor will be closely monitored during study treatment. If the tumor increases in size by 50% (half) or greater, study treatment will be stopped and you will immediately have surgery. If you have to stop treatment due to side effects from the drug(s), you may be able to start up again once the side effect has gone away or decreased in severity enough. However, the time you are off therapy will count towards the total 8 weeks that you can receive treatment. If recovery from the side effect requires a total of 8 weeks or more from the start of treatment, you will be removed from the study and receive surgery. Tumor and blood samples will be collected during surgery to check how the disease is responding to treatment.

Your routine surgery will be scheduled to take place up to 90 days following completion of your treatment and as soon as your blood counts have recovered to the normal level.

After surgery, if you are experiencing side effects from the study drugs, but show stable disease or you are responding to treatment, you will be able to receive 3 additional cycles of therapy (24 weeks). You will have a physical exam, including measurement of vital signs and routine blood tests (about 1 tablespoon) every 4 weeks. You will then be followed every 3 months with routine blood tests (about 1 tablespoon each time) for the first 3 years, and every 6 months up to 8 years. After that, follow-up will be at the discretion of your primary physician. CT scans of your chest, abdomen, and pelvis will be performed after each cycle of therapy for the 3 additional cycles, then every 6 months up to 5 years and then, at the discretion of your primary physician.

This is an investigational study. Temozolomide alone and given with pegylated interferon alpha-2b is authorized for use in research only. Neither of these drugs is currently approved by the FDA for this treatment. About 124 patients will be enrolled on this study. All will be enrolled at M. D. Anderson.

Arms: arm 1: 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. arm 2: 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.
Interventions: intervention 1: Temozolomide (TMZ) intervention 2: Pegylated Interferon Alpha-2b (PGI)
Intervention descriptions: intervention 1: 150 mg/m\^2 by mouth once daily for 7 days, followed by 7 days off (alternating weekly) for a total of 8 weeks. intervention 2: 0.5 mcg/kg subcutaneous injection once weekly for a total of 8 weeks.

Protocol documents: