Melanoma
Conditions
Keywords
Memorial Sloan-Kettering Cancer Center patients with measurable, unresectable stage, III or IV melanoma
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,
Interventions
DRUGTemozolomide (TMZ)
One group treatment study
Sponsors
Schering-Plough
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the Overall Objective Response Rate (CR and PR). | From start of treatment through 24 weeks after ending treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 18 months after ending treatment | Overall survival at 18 months post treatment |
| Duration of Objective Clinical Responses | 24 weeks after ending treatment | Duration of Response (Objective Clinical Responses) |
Countries
United States
Participant flow
Recruitment details
Protocol Open to Accrual-01/12/2005 Protocol Closed to Accrual-11/27/2007 Primary Completion Date-06/10/2008 Recruitment Location is the medical clinic
Participants by arm
| Arm | Count |
|---|---|
| Temozolomide (TMZ) Temozolomide (TMZ) 75 mg/m2/day x 6 weeks every 8 weeks | 51 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not Treated | 2 |
Baseline characteristics
| Characteristic | Temozolomide (TMZ) |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 27 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants |
| Region of Enrollment United States | 51 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 49 |
| serious Total, serious adverse events | 7 / 49 |
Outcome results
Primary
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.
Time frame: From start of treatment through 24 weeks after ending treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Temozolomide (TMZ) | Determine the Overall Objective Response Rate (CR and PR). | Complete Response | 0 participants |
| Temozolomide (TMZ) | Determine the Overall Objective Response Rate (CR and PR). | Partial Response | 6 participants |
| Temozolomide (TMZ) | Determine the Overall Objective Response Rate (CR and PR). | Stable Disease | 16 participants |
| Temozolomide (TMZ) | Determine the Overall Objective Response Rate (CR and PR). | Progression of Disease | 27 participants |
Secondary
Duration of Objective Clinical Responses
Duration of Response (Objective Clinical Responses)
Time frame: 24 weeks after ending treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Temozolomide (TMZ) | Duration of Objective Clinical Responses | 7.7 months |
Secondary
Overall Survival
Overall survival at 18 months post treatment
Time frame: 18 months after ending treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temozolomide (TMZ) | Overall Survival | 27 percentage of participants |