Sorafenib and Isolated Limb Infusion of Melphalan in Treating Patients With Stage III Melanoma of the Arm or Leg

NCT00565968 | Completed Phase 1

• 2 other identifiers: Pro00001344CDR0000575427
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. 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. Sorafenib may also make tumor cells more sensitive to melphalan. Giving sorafenib together with an isolated limb infusion of melphalan may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib when given together with an isolated limb infusion of melphalan in treating patients with stage III melanoma of the arm or leg.

Conditions

Melanoma (Skin)

Keywords

stage IIIB melanoma; stage IIIC melanoma; recurrent melanoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  1 year

Secondary Outcomes (5)

• Safety and tolerability

  2 years

• Antitumor activity, as evidenced by best overall response and duration of response

  3 years

• Duration of progression-free survival

  3 years

• Pharmacokinetics of melphalan

  3 years

• Tumor gene and protein expression profiles following treatment

  3 years

Study Arms (1)

Sorafenib dose escalation

EXPERIMENTAL

Drug: melphalan; Drug: sorafenib tosylate; Genetic: gene expression analysis; Genetic: protein expression analysis; Genetic: western blotting; Other: pharmacological study

Interventions

melphalan DRUG

Sorafenib dose escalation

sorafenib tosylate DRUG

Sorafenib dose escalation

gene expression analysis GENETIC

Sorafenib dose escalation

protein expression analysis GENETIC

Sorafenib dose escalation

western blotting GENETIC

Sorafenib dose escalation

pharmacological study OTHER

Sorafenib dose escalation

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed primary or recurrent extremity melanoma * Stage IIIB or IIIC disease * Patients with stage IIIC disease must have had regional lymph nodes previously removed * Disease to be treated by regional therapy must be distal to the planned site of tourniquet placement * Bidimensionally measurable disease by caliper or radiological method * Must have identifiable target lesions for disease assessment * Patients with a single lesion must have archived tumor tissue available for research analysis * No stage IV disease * No known brain metastasis * Patients with neurological symptoms must have undergone a CT scan or MRI of the brain within the past 4 weeks to exclude brain metastasis PATIENT CHARACTERISTICS: * ECOG or Zubrod performance status 0-1 * Life expectancy \> 6 months * Hemoglobin ≥ 9.0 g/dL * WBC ≥ 3,000/mm\^3 * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) * ALT and AST ≤ 2.5 x ULN * INR \< 1.5 or PT/PTT normal * Creatinine ≤ 1.5 x ULN * Not pregnant or nursing * Negative serum pregnancy test * Fertile patients must use effective contraception * Must have a palpable femoral or axillary pulse in the extremity to be treated * No cardiac disease, including any of the following: * NYHA class III or IV congestive heart failure * Unstable angina (i.e., angina symptoms at rest) or new onset angina within the past 3 months * Myocardial infarction within the past 6 months * No cardiac ventricular arrhythmias requiring antiarrhythmic therapy * No uncontrolled hypertension, defined as systolic blood pressure (BP) \> 150 mm Hg or diastolic BP \> 90 mm Hg, despite optimal medical management * No known HIV infection * No chronic hepatitis B or C * No active clinically serious infection \> CTCAE grade 2 * No thrombotic or embolic events (e.g., cerebrovascular accident or transient ischemic attacks) within the past 6 months * No signs or symptoms of vascular insufficiency (i.e., any history of blood clots or other ischemic peripheral vascular disease) * No evidence or history of bleeding diathesis or coagulopathy * No pulmonary hemorrhage or bleeding event ≥ CTCAE grade 2 within the past 4 weeks * No other hemorrhage or bleeding event ≥ CTCAE grade 3 within the past 4 weeks * No serious nonhealing wound, ulcer, or bone fracture * No significant traumatic injury within the past 4 weeks * No condition that impairs the patient's ability to swallow whole pills * No malabsorption problem * No known history of allergic reactions and/or hypersensitivity to melphalan, sorafenib tosylate, or any other agent used in the study * No psychiatric condition or diminished capacity that would compromise giving informed consent, or interfere with study compliance * No history of other malignancies, except for any of the following: * Adequately treated basal cell or squamous cell carcinoma of the skin * Curatively treated in situ carcinoma of the uterine cervix, prostate cancer, or superficial bladder cancer * Other curatively treated solid tumor with no evidence of disease for ≥ 5 years PRIOR CONCURRENT THERAPY: * Recovered from prior therapy * No prior sorafenib tosylate * Prior melphalan via isolated limb infusion allowed * No antineoplastic therapy, radiotherapy, or any other investigational drug within the past 4 weeks * No major surgery or open biopsy within the past 4 weeks * No concurrent Hypericum perforatum (St. John wort) or rifampin * Concurrent anti-coagulation treatment with warfarin or heparin allowed

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 (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Melphalan; Sorafenib; Gene Expression Profiling; Blotting, Western

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)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Genetic Techniques; Investigative Techniques; Electrophoresis; Chemistry Techniques, Analytical; Electrochemical Techniques; Immunoblotting; Immunoassay; Immunologic Techniques; Molecular Probe Techniques

Study Officials

• Douglas S. Tyler, MD

  Duke Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2007
• First Posted: November 30, 2007
• Study Start: October 1, 2007
• Primary Completion: August 1, 2009
• Last Updated: March 6, 2015

Record last verified: 2015-03

Locations

US (1)