SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma
Primary Purpose
Mucosal Lentiginous Melanoma, Acral Lentiginous Malignant Melanoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sunitinib
Sponsored by
About this trial
This is an interventional treatment trial for Mucosal Lentiginous Melanoma focused on measuring Sutent, malignant melanoma
Eligibility Criteria
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
Sites / Locations
- Massachusetts General Hospital
- Beth Israel Deaconess Medical Center
- Dana-Farber Cancer Institute
- Washington University in St. Louis
- Vanderbilt University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sunitinib
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Overall Survival
Overall survival (OS) is defined as the time from study entry to death or date last known alive.
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.
Full Information
NCT ID
NCT00577382
First Posted
December 18, 2007
Last Updated
October 16, 2016
Sponsor
Dana-Farber Cancer Institute
Collaborators
Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT00577382
Brief Title
SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma
Official Title
A Phase II Study of SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
August 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Pfizer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mucosal Lentiginous Melanoma, Acral Lentiginous Malignant Melanoma
Keywords
Sutent, malignant melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sunitinib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Sunitinib
Other Intervention Name(s)
Sutent, SU011248
Primary Outcome Measure Information:
Title
2-month Progression-free Survival Rate
Description
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.
Time Frame
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 Measure Information:
Title
Best Overall Response Rate
Description
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.
Time Frame
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.
Title
Overall Survival
Description
Overall survival (OS) is defined as the time from study entry to death or date last known alive.
Time Frame
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).
Title
Time to Progression
Description
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.
Time Frame
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).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
F. Stephen Hodi, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Washington University in St. Louis
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
26264378
Citation
Buchbinder EI, Sosman JA, Lawrence DP, McDermott DF, Ramaiya NH, Van den Abbeele AD, Linette GP, Giobbie-Hurder A, Hodi FS. Phase 2 study of sunitinib in patients with metastatic mucosal or acral melanoma. Cancer. 2015 Nov 15;121(22):4007-15. doi: 10.1002/cncr.29622. Epub 2015 Aug 11.
Results Reference
result
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SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma
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