Phase II Trial of Extended-Dosing Temozolomide in Patients With Melanoma

Temozolomide (also known as TMZ) is a chemotherapy drug given by mouth. It is similar to DTIC, the only FDA-approved chemotherapy for melanoma, but because temozolomide is given by mouth, it can be given daily over a long period of time. We think that temozolomidemay work best if it is given every day for 6 weeks at a time. Temozolomide given by this extended schedule is experimental, although we have found that it is safe and can shrink melanoma in some patients.

One big advantage of TMZ is that it is given by mouth instead of by vein. This means that it can be given daily over a long period of time rather than off and on like DTIC. We think that TMZ may work better if it is given every day for 6 weeks. TMZ given by this extended schedule is experimental although we have found that TMZ given in this way is safe and can shrink melanoma in some patients. When extended dosing TMZ was given with either thalidomide or long-acting interferon-α, about 30% of patients had their tumors shrink. We think that this shrinkage was due mostly to the TMZ since neither thalidomide nor interferon-α alpha work in melanoma by themselves.

In this study, we will treat patients with TMZ alone using this extended dosing schedule to see how many patients experience tumor shrinkage.

We also want to learn more about which tumors are more likely to shrink from TMZ treatment. We will test samples of your tumor for whether or not a gene called MGMT has been turned on,

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Drug: Temozolomide (TMZ)

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Stage III (unresectable) or Stage IV melanoma from a cutaneous or an unknown primary.
• Histologic proof of melanoma reviewed and confirmed at MSKCC
• Measurable disease (RECIST criteria)
• No prior chemotherapy for melanoma. Prior interferon, interleukin-2 or vaccine therapy are allowed.
• No other concurrent chemotherapy, immunotherapy, or radiotherapy
• Karnofsky performance status ≥ 60
• Adequate organ function defined as follows: ANC > 1500, Platelets > 100,000, creatinine < 2, Alkaline Phosphatase, AST and total bilirubin < 1.5x upper limit of normal. For patients with suspected Gilbert's syndrome bilirubin will not be a requirement.
• Tumor tissue for MGMT promoter methylation analysis and/or IHC must be available. In most cases, this will be unstained slides from previously-obtained paraffin-embedded tumor material. If this is not available, patients must have an easily-accessable tumor for biopsy (e.g. skin or lymph node).

Exclusion Criteria:

• History of CNS metastases unless brain metastases have been resected and the patient has been free from CNS recurrence for 6 months.
• Uveal or mucosal melanoma primary
• Frequent vomiting or medical conditions that could interfere with oral medication intake
• Serious infection requiring antibiotics, or nonmalignant medical illnesses that are uncontrolled or whose control might be jeopardized by the complications of this therapy.
• History of HIV infection even if on HAART
• Immunosuppressive drugs
• High dose vitamins and herbs
• Other on-going investigational therapy, concurrent chemotherapy, immunotherapy or radiotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 - Temozolomide (TMZ)	Drug: Temozolomide (TMZ); One group treatment study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the Overall Objective Response Rate (CR and PR).	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	From start of treatment through 24 weeks after ending treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival at 18 months post treatment	18 months after ending treatment
Duration of Objective Clinical Responses	Duration of Response (Objective Clinical Responses)	24 weeks after ending treatment

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Schering-Plough
• Investigators: Principal Investigator: Paul Chapman, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan-Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: December 26, 2007
• First Submitted That Met QC Criteria: January 10, 2008
• First Posted (Estimated): January 11, 2008

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Memorial Sloan-Kettering Cancer Center patients with measurable, unresectable stage; III or IV melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: 04-138