Brief Summary
This pilot clinical trial studies isolated limb perfusion with melphalan in treating patients with stage IIIB-IV melanoma or sarcoma. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Heating a chemotherapy solution and infusing it directly into the arteries around the tumor may kill more tumor cells.
Brief Title
Isolated Limb Perfusion With Melphalan in Treating Patients With Stage IIIB-IV Melanoma or Sarcoma
Detailed Description
PRIMARY OBJECTIVES:
I. This prospective trial will evaluate total response rate, including complete and partial response, in patients with unresectable extremity melanoma (or other skin cancer including but not limited to Merkel cell carcinoma) or soft tissue sarcoma treated with hyperthermic-isolated limb perfusion (ILP) with melphalan.
SECONDARY OBJECTIVES:
I. To evaluate the technical parameters including achievement of regional hyperthermia, arterial blood gas (ABG), tourniquet time, and their association with tumor response.
II. To evaluate time to recurrence and progression free survival (PFS) for patients with advanced extremity melanoma or sarcoma who achieved complete response after treatment with ILP with melphalan.
III. To evaluate overall survival rate and duration of survival for patients with advanced melanoma or sarcoma limited to extremity undergoing ILP with melphalan.
IV. To assess quality of life (QOL) score for patients undergoing ILP with melphalan.
OUTLINE:
Patients undergo ILP with melphalan intravenously (IV) over 60 minutes.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 4 months for 1 year, and then periodically thereafter.
I. This prospective trial will evaluate total response rate, including complete and partial response, in patients with unresectable extremity melanoma (or other skin cancer including but not limited to Merkel cell carcinoma) or soft tissue sarcoma treated with hyperthermic-isolated limb perfusion (ILP) with melphalan.
SECONDARY OBJECTIVES:
I. To evaluate the technical parameters including achievement of regional hyperthermia, arterial blood gas (ABG), tourniquet time, and their association with tumor response.
II. To evaluate time to recurrence and progression free survival (PFS) for patients with advanced extremity melanoma or sarcoma who achieved complete response after treatment with ILP with melphalan.
III. To evaluate overall survival rate and duration of survival for patients with advanced melanoma or sarcoma limited to extremity undergoing ILP with melphalan.
IV. To assess quality of life (QOL) score for patients undergoing ILP with melphalan.
OUTLINE:
Patients undergo ILP with melphalan intravenously (IV) over 60 minutes.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 4 months for 1 year, and then periodically thereafter.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Basal Cell Carcinoma of the Skin
Eccrine Carcinoma of the Skin
Recurrent Adult Soft Tissue Sarcoma
Recurrent Melanoma
Recurrent Skin Cancer
Squamous Cell Carcinoma of the Skin
Stage III Adult Soft Tissue Sarcoma
Stage IIIB Melanoma
Stage IIIC Melanoma
Stage IV Adult Soft Tissue Sarcoma
Stage IV Melanoma
Eligibility Criteria
Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* The patient must have histological-proven primary or recurrent extremity melanoma (or other skin cancer including but not limited to Merkel cell carcinoma) or sarcoma, stage IIIB, IIIC, or IV (American Joint Committee on Cancer \[AJCC\] staging must be documented in patient's medical record, as determined by computed tomography \[CT\] of the chest, abdomen and pelvis, and/or whole body positron emission tomography \[PET\] scan, within six weeks prior to administration of study drug)
* Patients with stage IV disease who have high tumor burden and extensive symptomatic extremity disease
* Patients with stage IIIC disease must either have had regional lymph nodes previously removed or will have them removed either at the time of regional treatment or soon thereafter
* Disease to be treated by ILP must be unresectable and distal to the planned site of tourniquet placement (which for the leg is generally the apex of the femoral triangle, or for the arm is distal to the deltoid insertion)
* Patient's disease must be bi-dimensionally measurable by caliper or radiological method as defined in the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (RECIST updated version 1.1); lesional tissue not necessary for diagnostic or other clinical purposes may be designated prospectively for research tissue banking
* Hemoglobin \>= 8.0 g/dl
* White blood count (WBC) of \>= 2000 m\^3
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Total bilirubin =\< 1.5 x upper limit of normal (ULN)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x the ULN
* Creatinine =\< 1.5 x ULN
* Patient must have a palpable femoral/radial pulse in the affected extremity
* Patients must have a life expectancy of \> 6 months
* Patient or the patient's legally acceptable representative must provide a signed and dated written informed consent prior to registration and any study-related procedures
* Patient or the patient's legally acceptable representative must provide written authorization to allow the use and disclosure of their protected health information at any institution subject to United States Health Insurance Portability and Accountability Act (US HIPAA) regulations; NOTE: This may be obtained in either the study-specific informed consent or in a separate authorization form and must be obtained from the patient prior to study registration
Exclusion Criteria:
* Cardiac disease: congestive heart failure \> class II New York Heart Association (NYHA); patients must not have unstable angina (angina symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
* Known brain metastasis; patients with neurological symptoms must undergo a CT scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis
* Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
* Active clinically serious infection \> Common Terminology Criteria for Adverse Events (CTCAE) grade 2
* Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
* Pulmonary hemorrhage/bleeding event \>= CTCAE grade 2 within 4 weeks of ILP/isolated limb infusion (ILI); any other hemorrhage/bleeding event \>= CTCAE grade 3 within 4 weeks ILP/ILI
* Major surgery or significant traumatic injury within 30 days of ILI/ILP
* Evidence or history of bleeding diathesis or coagulopathy
* Antineoplastic therapy, radiotherapy, or any other investigational drug within 30 days prior to first study drug administration
* Patients with symptoms or signs of vascular insufficiency; specifically, patients with any history of blood clots or lifestyle altering ischemic peripheral vascular disease will be excluded
* History of allergic reactions and/or hypersensitivity to melphalan
* Psychiatric conditions or diminished capacity that could compromise the giving of informed consent, or interfere with study compliance
* Pregnant or nursing women are not eligible for this study
* Unable to return at the regular required intervals for reassessment, or study drug administration
* Patients with known heparin induced thrombocytopenia
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* The patient must have histological-proven primary or recurrent extremity melanoma (or other skin cancer including but not limited to Merkel cell carcinoma) or sarcoma, stage IIIB, IIIC, or IV (American Joint Committee on Cancer \[AJCC\] staging must be documented in patient's medical record, as determined by computed tomography \[CT\] of the chest, abdomen and pelvis, and/or whole body positron emission tomography \[PET\] scan, within six weeks prior to administration of study drug)
* Patients with stage IV disease who have high tumor burden and extensive symptomatic extremity disease
* Patients with stage IIIC disease must either have had regional lymph nodes previously removed or will have them removed either at the time of regional treatment or soon thereafter
* Disease to be treated by ILP must be unresectable and distal to the planned site of tourniquet placement (which for the leg is generally the apex of the femoral triangle, or for the arm is distal to the deltoid insertion)
* Patient's disease must be bi-dimensionally measurable by caliper or radiological method as defined in the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (RECIST updated version 1.1); lesional tissue not necessary for diagnostic or other clinical purposes may be designated prospectively for research tissue banking
* Hemoglobin \>= 8.0 g/dl
* White blood count (WBC) of \>= 2000 m\^3
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Total bilirubin =\< 1.5 x upper limit of normal (ULN)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x the ULN
* Creatinine =\< 1.5 x ULN
* Patient must have a palpable femoral/radial pulse in the affected extremity
* Patients must have a life expectancy of \> 6 months
* Patient or the patient's legally acceptable representative must provide a signed and dated written informed consent prior to registration and any study-related procedures
* Patient or the patient's legally acceptable representative must provide written authorization to allow the use and disclosure of their protected health information at any institution subject to United States Health Insurance Portability and Accountability Act (US HIPAA) regulations; NOTE: This may be obtained in either the study-specific informed consent or in a separate authorization form and must be obtained from the patient prior to study registration
Exclusion Criteria:
* Cardiac disease: congestive heart failure \> class II New York Heart Association (NYHA); patients must not have unstable angina (angina symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
* Known brain metastasis; patients with neurological symptoms must undergo a CT scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis
* Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
* Active clinically serious infection \> Common Terminology Criteria for Adverse Events (CTCAE) grade 2
* Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
* Pulmonary hemorrhage/bleeding event \>= CTCAE grade 2 within 4 weeks of ILP/isolated limb infusion (ILI); any other hemorrhage/bleeding event \>= CTCAE grade 3 within 4 weeks ILP/ILI
* Major surgery or significant traumatic injury within 30 days of ILI/ILP
* Evidence or history of bleeding diathesis or coagulopathy
* Antineoplastic therapy, radiotherapy, or any other investigational drug within 30 days prior to first study drug administration
* Patients with symptoms or signs of vascular insufficiency; specifically, patients with any history of blood clots or lifestyle altering ischemic peripheral vascular disease will be excluded
* History of allergic reactions and/or hypersensitivity to melphalan
* Psychiatric conditions or diminished capacity that could compromise the giving of informed consent, or interfere with study compliance
* Pregnant or nursing women are not eligible for this study
* Unable to return at the regular required intervals for reassessment, or study drug administration
* Patients with known heparin induced thrombocytopenia
Inclusion Criteria
Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* The patient must have histological-proven primary or recurrent extremity melanoma (or other skin cancer including but not limited to Merkel cell carcinoma) or sarcoma, stage IIIB, IIIC, or IV (American Joint Committee on Cancer \[AJCC\] staging must be documented in patient's medical record, as determined by computed tomography \[CT\] of the chest, abdomen and pelvis, and/or whole body positron emission tomography \[PET\] scan, within six weeks prior to administration of study drug)
* Patients with stage IV disease who have high tumor burden and extensive symptomatic extremity disease
* Patients with stage IIIC disease must either have had regional lymph nodes previously removed or will have them removed either at the time of regional treatment or soon thereafter
* Disease to be treated by ILP must be unresectable and distal to the planned site of tourniquet placement (which for the leg is generally the apex of the femoral triangle, or for the arm is distal to the deltoid insertion)
* Patient's disease must be bi-dimensionally measurable by caliper or radiological method as defined in the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (RECIST updated version 1.1); lesional tissue not necessary for diagnostic or other clinical purposes may be designated prospectively for research tissue banking
* Hemoglobin \>= 8.0 g/dl
* White blood count (WBC) of \>= 2000 m\^3
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Total bilirubin =\< 1.5 x upper limit of normal (ULN)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x the ULN
* Creatinine =\< 1.5 x ULN
* Patient must have a palpable femoral/radial pulse in the affected extremity
* Patients must have a life expectancy of \> 6 months
* Patient or the patient's legally acceptable representative must provide a signed and dated written informed consent prior to registration and any study-related procedures
* Patient or the patient's legally acceptable representative must provide written authorization to allow the use and disclosure of their protected health information at any institution subject to United States Health Insurance Portability and Accountability Act (US HIPAA) regulations; NOTE: This may be obtained in either the study-specific informed consent or in a separate authorization form and must be obtained from the patient prior to study registration
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* The patient must have histological-proven primary or recurrent extremity melanoma (or other skin cancer including but not limited to Merkel cell carcinoma) or sarcoma, stage IIIB, IIIC, or IV (American Joint Committee on Cancer \[AJCC\] staging must be documented in patient's medical record, as determined by computed tomography \[CT\] of the chest, abdomen and pelvis, and/or whole body positron emission tomography \[PET\] scan, within six weeks prior to administration of study drug)
* Patients with stage IV disease who have high tumor burden and extensive symptomatic extremity disease
* Patients with stage IIIC disease must either have had regional lymph nodes previously removed or will have them removed either at the time of regional treatment or soon thereafter
* Disease to be treated by ILP must be unresectable and distal to the planned site of tourniquet placement (which for the leg is generally the apex of the femoral triangle, or for the arm is distal to the deltoid insertion)
* Patient's disease must be bi-dimensionally measurable by caliper or radiological method as defined in the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (RECIST updated version 1.1); lesional tissue not necessary for diagnostic or other clinical purposes may be designated prospectively for research tissue banking
* Hemoglobin \>= 8.0 g/dl
* White blood count (WBC) of \>= 2000 m\^3
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Total bilirubin =\< 1.5 x upper limit of normal (ULN)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x the ULN
* Creatinine =\< 1.5 x ULN
* Patient must have a palpable femoral/radial pulse in the affected extremity
* Patients must have a life expectancy of \> 6 months
* Patient or the patient's legally acceptable representative must provide a signed and dated written informed consent prior to registration and any study-related procedures
* Patient or the patient's legally acceptable representative must provide written authorization to allow the use and disclosure of their protected health information at any institution subject to United States Health Insurance Portability and Accountability Act (US HIPAA) regulations; NOTE: This may be obtained in either the study-specific informed consent or in a separate authorization form and must be obtained from the patient prior to study registration
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02507076
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
11-12-411
Overall Status
Withdrawn
Phases
Not Applicable
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Isolated Limb Perfusion for Advanced Melanoma or Sarcoma Limited to Extremity With or Without Distant Metastases
Primary Outcomes
Outcome Description
Rates of complete and partial response will be computed and reported with their 95% confidence intervals.
Outcome Measure
Overall response rate (complete and partial response) assessed by the RECIST v1.1
Outcome Time Frame
Up to 12 weeks
Secondary Ids
Secondary Id
NCI-2013-01218
Secondary Id
11-103
Secondary Id
11-12-411
Secondary Id
P30CA013330
Secondary Outcomes
Outcome Description
Kaplan-Meier methods will be used. 95% confidence intervals will be computed using Greenwood's formula.
Outcome Time Frame
Up to 4 years
Outcome Measure
Time to recurrence
Outcome Description
Kaplan-Meier methods will be used. 95% confidence intervals will be computed using Greenwood's formula.
Outcome Time Frame
Time of ILP procedure to date of recurrence, assessed up to 4 years
Outcome Measure
Progression-free survival
Outcome Description
Kaplan-Meier methods will be used. 95% confidence intervals will be computed using Greenwood's formula.
Outcome Time Frame
Time of ILP treatment to time of death, assessed up to 4 years
Outcome Measure
Overall survival
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Katia Papalezova
Investigator Email
kpapalez@montefiore.org
Investigator Phone