SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate how effective Sunitinib works in treating acral lentiginous and mucosal melanoma which has spread beyond the local region. Suninitib is a protein-tyrosine kinase inhibitor and acts as a c-kit inhibitor drug. It is believed to work by blocking signals on certain cancer cells which allow the malignant cells to multiply and spread due to a change in the genetic make up of the cancer cell.

Detailed Description
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OBJECTIVES: Primary To determine the proportion of participants with metastatic mucosal or acral/lentiginous melanoma who are alive and without disease progression at two months after beginning treatment with sunitinib. To determine the best overall response rate. Secondary To determine the time to progression and overall survival. To correlate c-kit mutational status with response to therapy. To evaluate the use of FDG-PET scanning in determining early biologic response to therapy. To assess amplification of c-kit status through quantitative PCR and/or FISH and other related molecular pathway targets.

Official Title
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A Phase II Study of SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma

Conditions
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Mucosal Lentiginous Melanoma, Acral Lentiginous Malignant Melanoma

Intervention / Treatment
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* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of primary mucosal or acral/lentiginous melanoma Histologically documented stage III unresectable or IV metastatic melanoma ECOG Performance Status 0,1 or 2 Estimated life expectancy of 6 months or greater 18 years of age or older Lab values as outlined in protocol Tumor blocks or slides must be available of either primary or metastatic tumor site for c-kit mutation testing Negative pregnancy test within 48 hours of starting treatment At least one measurable site of disease as defined by at least 1cm in greatest dimension Exclusion Criteria: Severe and/or uncontrolled medical disease Pregnant or nursing mothers Known brain metastasis. History of or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan Less than 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or cervical carcinoma in situ Grade III/IV cardiac problems as defined by the New York Heart Association Criteria Ongoing cardiac dysrhythmias of grade 2 or greater, atrial fibrillation, QTc interval >450msec for males of >470 msec for females Hypertension that cannot be controlled by medication Any of the following within 12 months prior to starting treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism NCI CTCAE version 3.0 grade 3 hemorrhage within 4 weeks of starting the study treatment Concurrent treatment with warfarin Prior treatment with SU011248 or any other antiangiogenic agent No H2 blockers or proton pump inhibitors Known chronic liver disease Known HIV infection Previous radiotherapy to 25% or more of the bone marrow and/or radiation therapy within 4 weeks prior to study entry Major surgery within 4 weeks prior to study entry Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sunitinib<br>Cohort A participants received 50 mg sunitinib orally daily for 4 weeks followed by a two-week break from treatment. These 6-week cycles would be repeated until progression or unacceptable toxicity up to 1 year. Cohort B participants received 37.5 mg sunitinib daily on a continuous basis until progression or unacceptable toxicity up to 1 year. | Drug: Sunitinib<br> <br> * Other names: SU011248;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-month Progression-free Survival Rate | 2-month progression-free survival rate was defined as the proportion of patients absent death or progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) before 2 months. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. | Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued for 12 months unless disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 2 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response Rate | The best overall response rate was defined as achieving partial response (PR) or complete response (CR) on treatment based on RECIST 1.0 criteria. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. | Disease was evaluated radiologically at baseline and every 8 weeks on treatment. Mean treatment duration was 3 cycles (Cohort A/B mean 2/3 cycles). The range of treatment duration overall was 1-11 cycles. | 
| Overall Survival | Overall survival (OS) is defined as the time from study entry to death or date last known alive. | Patients were followed long-term every 3 months until first progression, death or lost to follow-up. Median survival follow-up was 6.7 months (range 0.8-47.3 months; Cohort A/B median 7.7 m/ 6.2 m). | 
| Time to Progression | Time to progression based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. | Disease was evaluated radiologically at baseline and every 8 weeks on treatment and long-term every 3 months until first progression, death or lost to follow-up. Mean treatment duration was 3 cycles (range 1-11; Cohort A/B mean 2/3 cycles). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sutent, malignant melanoma