Isolated Limb Perfusion With Melphalan in Treating Patients With Stage IIIB-IV Melanoma or Sarcoma

Stage IV Melanoma Clinical Trial

Official title:

Isolated Limb Perfusion for Advanced Melanoma or Sarcoma Limited to Extremity With or Without Distant Metastases

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02507076
• Other study ID #: 11-12-411
• Secondary ID: NCI-2013-0121811
• Status: Withdrawn
• Phase: N/A
• First received: July 22, 2015
• Last updated: July 22, 2015
• Start date: April 2012
• Est. completion date: July 2014

Study information

• Verified date: July 2015
• Source: Albert Einstein College of Medicine of Yeshiva University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Basal Cell Carcinoma of the Skin
• Carcinoma
• Carcinoma, Basal Cell
• Carcinoma, Squamous Cell
• Eccrine Carcinoma of the Skin
• Melanoma
• Recurrent Adult Soft Tissue Sarcoma
• Recurrent Melanoma
• Recurrent Skin Cancer
• Sarcoma
• Skin Neoplasms
• 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

Intervention

Drug:
• isolated limb perfusion
Undergo ILP with melphalan
• melphalan
Undergo ILP with melphalan

Procedure:
• quality-of-life assessment
Ancillary studies

Locations

Country	Name	City	State
United States	Albert Einstein College of Medicine	Bronx	New York

Sponsors (2)

Lead Sponsor	Collaborator
Albert Einstein College of Medicine of Yeshiva University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate (complete and partial response) assessed by the RECIST v1.1	Rates of complete and partial response will be computed and reported with their 95% confidence intervals.	Up to 12 weeks	No
Secondary	Time to recurrence	Kaplan-Meier methods will be used. 95% confidence intervals will be computed using Greenwood's formula.	Up to 4 years	No
Secondary	Progression-free survival	Kaplan-Meier methods will be used. 95% confidence intervals will be computed using Greenwood's formula.	Time of ILP procedure to date of recurrence, assessed up to 4 years	No
Secondary	Overall survival	Kaplan-Meier methods will be used. 95% confidence intervals will be computed using Greenwood's formula.	Time of ILP treatment to time of death, assessed up to 4 years	No