Clinical trial NCT00591370: Phase II Trial of Extended-Dosing Temozolomide in Patients With Melanoma
Official title: Phase II Trial of Extended-Dosing Temozolomide in Patients With Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma
Keywords: Memorial Sloan-Kettering Cancer Center patients with measurable, unresectable stage
III or IV melanoma
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Schering-Plough
First posted: 2008-01-11
Enrollment: 51
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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,


Eligibility criteria: 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.

Primary outcomes:
measure: Determine the Overall Objective Response Rate (CR and PR).
timeFrame: From start of treatment through 24 weeks after ending treatment
Secondary outcomes:
measure: Overall Survival
timeFrame: 18 months after ending treatment
measure: Duration of Objective Clinical Responses
timeFrame: 24 weeks after ending treatment
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Paul Chapman, MD
role: PRINCIPAL_INVESTIGATOR
References: