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A Randomized Phase III Trial of Hyperthermic Isolated Limb Perfusion and Melphalan With and Without Tumor Necrosis Factor in Patients With Localized Advanced Extremity Melanoma


Phase 3
18 Years
N/A
Not Enrolling
Both
Recurrent Melanoma, Stage III Melanoma

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Trial Information

A Randomized Phase III Trial of Hyperthermic Isolated Limb Perfusion and Melphalan With and Without Tumor Necrosis Factor in Patients With Localized Advanced Extremity Melanoma


OBJECTIVES:

I. Compare hyperthermic isolated limb perfusion with melphalan with or without tumor
necrosis factor, in terms of response proportion for lesions in the perfusion field, in
patients with locally advanced extremity melanoma.

II. Compare the local recurrence-free survival, improvement in regional symptoms related to
tumor, and overall survival in patients treated with these regimens.

III. Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor
burden (high vs low), prior reperfusion (melphalan vs other), regional nodal site (yes vs
no), and participating center. Patients are randomized to one of two treatment arms.

ARM I: Patients undergo hyperthermic isolated perfusions of the lower limb by either the
external iliac vessels or the common femoral vessels. Patients undergo perfusions of the
upper extremity by the axillary artery and vein using an infraclavicular/axillary incision.
Melphalan is introduced into the perfusion by slow injection over 5 minutes and allowed to
remain for a total of 60 minutes.

ARM II: Patients undergo hyperthermic isolated perfusions as in arm I. Tumor necrosis factor
is administered by slow injection into the arterial line and allowed to remain for a total
of 90 minutes. Melphalan is introduced into the perfusion as in arm I and allowed to remain
for a total of 60 minutes.

Patients are followed within 6 weeks, at 3, 6, and 12 months, every 6 months for 4 years,
and then annually thereafter.


Inclusion Criteria:



- Histologically proven locally advanced melanoma of an extremity

- One or more evaluable in-transit metastases

- All disease within the perfusion field of the extremity (with no local
resection options short of amputation)

- Disease outside of perfusion field (with no local resection options short of
amputation) if all the following are true:

- High tumor burden (more than 10 lesions or any single lesion greater than
3 cm)

- Presence of pain, edema, skin breakdown, or decreased mobility

- Greater than 80% of known tumor is within extremity perfusion field

- Life expectancy more than 6 months

- No brain metastases

- At least 1 bidimensionally measurable lesion

- Patients who received prior prophylactic isolated limb perfusion (ILP) must have 1 of
the following:

- Disease-free interval for at least 6 months after prior ILP with melphalan

- Disease-free interval for at least 3 months after prior ILP with an agent other
than melphalan

- Patients who received prior therapeutic ILP must have 1 of the following:

- Partial response of at least 3 months duration after prior ILP with melphalan

- Stable response or disease progression after ILP without melphalan (performed at
least 3 months prior to study)

- Performance status - ECOG 0-2

- Performance status - Zubrod 0-2

- See Disease Characteristics

- Platelet count at least 100,000/mm^3

- WBC greater than 2,500/mm^3

- Hemoglobin greater than 9 g/dL

- Bilirubin less than 1.25 times ULN

- AST and ALT less than 2 times ULN

- Alkaline phosphatase less than 2 times ULN

- Coagulation studies normal or within 1 second of upper limit of normal (ULN)

- Creatinine less than 1.5 mg/dL

- Creatinine clearance greater than 50 mL/min

- Calcium less than 12 mg/dL

- No severe peripheral vascular disease (claudication or other ischemic peripheral
vascular disease [e.g., venous thrombosis or occlusive peripheral arterial disease])

- No New York Heart Association class II-IV heart disease (congestive heart failure)

- No uncontrolled or life-threatening cardiac arrhythmia

- No myocardial infarction within the past year

- No unstable angina

- No symptomatic cerebral or carotid artery disease

- No pulmonary embolism within the past year

- Other prior malignancy allowed if completed curative therapy, disease-free for at
least 5 years, and at low risk for recurrence

- No active peptic ulcer disease within the past year

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No known melphalan hypersensitivity

- No known hypersensitivity to any component of tumor necrosis factor alpha formulation

- No contraindications to ionotropic agents (e.g., dopamine or neosynephrine)

- No concurrent infections uncontrolled with antibiotics

- HIV negative

- At least 1 month since prior biologic therapy

- See Disease Characteristics

- At least 1 month since prior chemotherapy

- At least 4 months since prior isolated limb perfusion

- At least 1 month since prior radiotherapy

- See Disease Characteristics

- At least 12 months since prior coronary artery surgery or angioplasty

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

CR proportion

Outcome Description:

Response will be calculated based on the 3-month follow-up assessment of presence of absence of complete response. This will be done using the logistic regression model.

Outcome Time Frame:

Up to 3 months after completion of study treatment

Safety Issue:

No

Principal Investigator

Douglas Fraker

Investigator Role:

Principal Investigator

Investigator Affiliation:

American College of Surgeons

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01843

NCT ID:

NCT00003789

Start Date:

March 1999

Completion Date:

Related Keywords:

  • Recurrent Melanoma
  • Stage III Melanoma
  • Melanoma
  • Necrosis

Name

Location

American College of Surgeons Oncology GroupDurham, North Carolina  27705