This site became the new on June 19th. Learn more.
Show more Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more... Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more... Menu
Give us feedback

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

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Duke University Identifier:
First received: November 29, 2007
Last updated: March 5, 2015
Last verified: March 2015

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.

Condition Intervention Phase
Melanoma (Skin) Drug: melphalan Drug: sorafenib tosylate Genetic: gene expression analysis Genetic: protein expression analysis Genetic: western blotting Other: pharmacological study Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Trial to Evaluate Safety and Efficacy of Oral Sorafenib (Nexavar) With Regional Melphalan Via Normothermic Isolated Limb Infusion (ILI) in Patients With Intransit Extremity Melanoma

Resource links provided by NLM:

Further study details as provided by Duke University:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: 1 year ]

Secondary Outcome Measures:
  • Safety and tolerability [ Time Frame: 2 years ]
  • Antitumor activity, as evidenced by best overall response and duration of response [ Time Frame: 3 years ]
  • Duration of progression-free survival [ Time Frame: 3 years ]
  • Pharmacokinetics of melphalan [ Time Frame: 3 years ]
  • Tumor gene and protein expression profiles following treatment [ Time Frame: 3 years ]

Enrollment: 20
Study Start Date: October 2007
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib dose escalation Drug: melphalan Drug: sorafenib tosylate Genetic: gene expression analysis Genetic: protein expression analysis Genetic: western blotting Other: pharmacological study

Detailed Description:



  • To determine the dose-limiting toxicities and maximum tolerate dose of systemic sorafenib tosylate in combination with regionally administered melphalan by isolated limb infusion in patients with stage IIIB or IIIC intransit extremity melanoma.


  • To characterize the safety and tolerability of this regimen in these patients.
  • To assess the antitumor activity of this regimen, as evidenced by best overall response and duration of response, in these patients.
  • To characterize the duration of progression-free survival of these patients.
  • To characterize the pharmacokinetics of melphalan.
  • To assess alterations in selected gene and protein expression profiles following treatment.

OUTLINE: This is a multicenter, dose-escalation study of sorafenib tosylate.

Patients receive oral sorafenib tosylate twice daily on days 1-14 and melphalan via isolated limb infusion into the upper or lower extremities on day 8.

Patients undergo tumor biopsies at baseline and in weeks 2 and 12 for gene expression analysis and western blot analysis. Patients also undergo blood sample collection periodically for pharmacokinetic analysis of melphalan.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 2 years.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00565968

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Duke University
National Cancer Institute (NCI)
Principal Investigator: Douglas S. Tyler, MD Duke Cancer Institute
  More Information

Responsible Party: Duke University Identifier: NCT00565968     History of Changes
Other Study ID Numbers: Pro00001344
Study First Received: November 29, 2007
Last Updated: March 5, 2015

Keywords provided by Duke University:
stage IIIB melanoma
stage IIIC melanoma
recurrent melanoma

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors processed this record on August 18, 2017