A Phase I Trial of Normothermic Isolated Limb Infusion (ILI) With Melphalan Plus Buthionine Sulfoximine (BSO) in Patients With Locally Advanced Malignant Melanoma

NCT00661336 | Withdrawn Phase 1

• 2 other identifiers: Pro00001793DUMC-PRO00001793
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Buthionine sulfoximine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Sometimes when chemotherapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to chemotherapy. Giving buthionine sulfoximine together with chemotherapy may reduce drug resistance and allow the tumor cells to be killed. PURPOSE: This phase I trial is studying the side effects and best dose of melphalan when given as an isolated limb infusion together with buthionine sulfoximine in treating patients with persistent or recurrent stage III malignant melanoma.

Conditions

Melanoma (Skin)

Keywords

stage III melanoma; recurrent melanoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of melphalan when administered as an isolated limb infusion in combination with a systemic infusion of buthionine sulfoximine (BSO)

Secondary Outcomes (8)

• Dose-limiting toxicity of regional melphalan when administered with systemic BSO

• Clinical response

• Effectiveness of systemic BSO in decreasing tumor glutathione (GSH) levels and its effect on GST activity and GST expression

• Correlation between tumor GSH levels and GSH levels in peripheral blood mononuclear cells to determine if the latter can serve as a surrogate marker for tumor GSH depletion

• Pharmacokinetics

Interventions

buthionine sulfoximine DRUG

melphalan DRUG

microarray analysis GENETIC

high performance liquid chromatography OTHER

laboratory biomarker analysis OTHER

pharmacological study OTHER

biopsy PROCEDURE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically proven primary or recurrent in-transit melanoma of the extremity * Stage IIIB or IIIC disease, as determined by whole body imaging with a CT scan of the chest, abdomen, and pelvis AND PET scan within the past 4 weeks * Patients with stage IIIC disease must have undergone removal of regional lymph nodes * Patients with indeterminate staging must be reviewed by the study chairs prior to study registration * Previously treated with melphalan-based regional therapy and had persistent disease at 3 months OR achieved a complete response but disease recurred within 6 months * Disease to be treated by regional therapy must be distal to the planned site of tourniquet placement * Bidimensionally measurable disease by caliper or a radiological method as defined by the RECIST criteria modified for cutaneous lesions * Photo documentation required * Patients with a single lesion must have archived tumor tissue available for study analysis * No history of tumors with clinically significant evidence of active bleeding (e.g., gross hemoptysis, hematemesis, hematuria, melena, or bleeding superficial tumor) within the past 12 weeks * No stage IV disease * No cerebral metastases PATIENT CHARACTERISTICS: * ECOG/Zubrod performance status 0-1 * Serum creatinine ≤ 1.5 mg/dL * WBC ≥ 3,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 10 g/dL * Bilirubin normal * AST and ALT ≤ 2.5 times normal * Must have a palpable femoral/axillary pulse in the affected extremity * No uncontrolled seizures or clinically significant CNS disorders * No psychiatric condition or diminished capacity that could preclude study compliance or giving informed consent * No history of allergic reactions and/or hypersensitivity to melphalan * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No history of other malignancies except adequately treated basal cell or squamous cell carcinoma of the skin; curatively treated carcinoma in situ of the uterine cervix, prostate cancer, or superficial bladder cancer; or other curatively treated solid tumors with no evidence of disease for ≥ 5 years * No stroke or other major tissue injury within the past 4 weeks * No other uncontrolled serious chronic disease or condition that, in the investigator's opinion, could preclude study compliance or follow-up PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from prior therapy * More than 4 weeks since prior major surgery * Wound healing adequate since last major surgery * More than 4 weeks since prior antineoplastic therapy, radiotherapy, or any other investigational drug * More than 7 days since prior antimicrobial agents (i.e., antibiotic, antifungal, or antiviral agents) for active infection or infectious symptoms * No drugs that are known to cause enhanced glutathione depletion (e.g., acetaminophen) for 7 days before, during, and for 7 days after buthionine sulfoximine (BSO) administration * No cephalosporin antibiotics for 7 days before, during, and for 7 days after BSO administration

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Duke University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Buthionine Sulfoximine; Melphalan; Microarray Analysis; Chromatography, High Pressure Liquid; Biopsy

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Methionine Sulfoximine; Methionine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Microchip Analytical Procedures; Investigative Techniques; Chromatography, Liquid; Chromatography; Chemistry Techniques, Analytical; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Douglas S. Tyler, MD

  Duke Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2008
• First Posted: April 18, 2008
• Study Start: April 1, 2008
• Primary Completion: December 1, 2009
• Last Updated: March 13, 2015

Record last verified: 2010-04

Locations

US (2)