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Pilot Study of a Double Isolation Perfusion Schedule Using Melphalan Alone for Intransit Melanoma or Unresectable Sarcoma of the Extremity

Primary Purpose

Melanoma, Sarcoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
double isolated limb perfusion with melphalan alone
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Chemotherapy, Hyperthermia, Isolation perfusion, Regional Therapy

Eligibility Criteria

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DISEASE CHARACTERISTICS: Histologically confirmed unresectable sarcoma or intransit melanoma of the upper or lower extremity. Extremity sarcoma with no local resection option and would require amputation based upon abutment or proximity of the tumor to major neurovascular structures or bone or joint structures. MELANOMA PATIENTS: Must have history of two or more satellite intransit metastases of which one may be excised for diagnosis with the exception of patients with a single, large, deep, locally recurrent tumor or metastatic tumor (greater than 5 cm) that precludes an excision with primary closure. Stage IV melanoma must have a significant component (greater than 90%) of disease distal to the apex of the femoral triangle in the lower limb or distal to the insertion of the deltoid in the upper limb. Must have evaluable disease in the extremity. Melanoma must have dermal or subcutaneous lesion that can be measure directly in two diameters to assess tumor burden. Sarcoma must have either cutaneous lesions amenable to direct measurement or deeper lesions that can be measured on CT or MRI scans. PRIOR/CONCURRENT THERAPY: At least 2 months since any regional therapy to the affected extremity. BIOLOGIC THERAPY: At least 1 month since Biologic Therapy. CHEMOTHERAPY: At least 1 month since chemotherapy. ENDOCRINE THERAPY: Not specified. RADIOTHERAPY: At least 1 month since radiotherapy. SURGERY: Not specified. PATIENT CHARACTERISTICS: AGE: 18 and over. PERFORMANCE STATUS: ECOG 0-2. LIFE EXPECTANCY: At least 6 months. HEMATOPOIETIC: Platelet count greater than 150,000/mm(3). HEPATIC: Bilirubin less than 2.0 mg/dL. RENAL: Creatinine less than 2.0 mg/dL. CARDIOVASCULAR: No history of congestive heart failure with an LVEF less than 40%. PULMONARY: No chronic obstructive pulmonary disease. No other chronic pulmonary disease with PFTs less than 50% predicted for age. OTHER: IF HIV POSITIVE: Must have CD4 cell count greater than 500/mL and, No clinical manifestations of AIDS. Coagulation parameters no greater than 1-2 seconds within the upper limit of normal. No evidence of severe peripheral vascular disease. No history of claudication or other ischemic vascular disease. Not pregnant or nursing.

Sites / Locations

  • National Cancer Institute (NCI)

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 3, 1999
Last Updated
March 3, 2008
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00001577
Brief Title
Pilot Study of a Double Isolation Perfusion Schedule Using Melphalan Alone for Intransit Melanoma or Unresectable Sarcoma of the Extremity
Official Title
Pilot Study of a Double Isolation Perfusion Schedule Using Melphalan Alone for Intransit Melanoma or Unresectable Sarcoma of the Extremity
Study Type
Interventional

2. Study Status

Record Verification Date
April 1999
Overall Recruitment Status
Completed
Study Start Date
June 1997 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 2000 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
Hyperthermic isolated limb perfusion with melphalan alone is administered as a double perfusion schedule. These two isolates limb perfusions with melphalan are treated 3-6 weeks apart. After perfusion is established, the leak rate has been determined to be acceptable, and tissue temperatures are 38 degrees Celsius, then the melphalan is administered by slow injection into an arterial line over approximately 5 minutes. The perfusion with melphalan will then continue for 60 minutes, after which the extremity is flushed out with a total of 3 liters of fluid consisting initially of a saline solution. The dose of melphalan for the second perfusion will be increased. An attempt to resect the residual lesion between 6-12 weeks after the second interval perfusion may be made.
Detailed Description
Patients with extremity melanoma (Stage IIIA, IIIAB or Stage IV disease who have bulky symptomatic tumor located in the extremity) or patients with unresectable extremity sarcoma will undergo a double isolated limb perfusion with melphalan alone separated by approximately 4 to 6 weeks. The initial perfusion will be done with a melphalan dose of 6 mg/L limb volume and the interval perfusion with a dose of 9 mg/L limb volume. For patients with extremity sarcoma the tumor will be excised if feasible using a limb sparing resection between 6-12 weeks after the second perfusion. Technical feasibility of the double perfusion schedule will be determined. Overall response, duration of response, patterns of recurrence, and survival will be followed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma, Sarcoma
Keywords
Chemotherapy, Hyperthermia, Isolation perfusion, Regional Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
30 (false)

8. Arms, Groups, and Interventions

Intervention Type
Procedure
Intervention Name(s)
double isolated limb perfusion with melphalan alone

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed unresectable sarcoma or intransit melanoma of the upper or lower extremity. Extremity sarcoma with no local resection option and would require amputation based upon abutment or proximity of the tumor to major neurovascular structures or bone or joint structures. MELANOMA PATIENTS: Must have history of two or more satellite intransit metastases of which one may be excised for diagnosis with the exception of patients with a single, large, deep, locally recurrent tumor or metastatic tumor (greater than 5 cm) that precludes an excision with primary closure. Stage IV melanoma must have a significant component (greater than 90%) of disease distal to the apex of the femoral triangle in the lower limb or distal to the insertion of the deltoid in the upper limb. Must have evaluable disease in the extremity. Melanoma must have dermal or subcutaneous lesion that can be measure directly in two diameters to assess tumor burden. Sarcoma must have either cutaneous lesions amenable to direct measurement or deeper lesions that can be measured on CT or MRI scans. PRIOR/CONCURRENT THERAPY: At least 2 months since any regional therapy to the affected extremity. BIOLOGIC THERAPY: At least 1 month since Biologic Therapy. CHEMOTHERAPY: At least 1 month since chemotherapy. ENDOCRINE THERAPY: Not specified. RADIOTHERAPY: At least 1 month since radiotherapy. SURGERY: Not specified. PATIENT CHARACTERISTICS: AGE: 18 and over. PERFORMANCE STATUS: ECOG 0-2. LIFE EXPECTANCY: At least 6 months. HEMATOPOIETIC: Platelet count greater than 150,000/mm(3). HEPATIC: Bilirubin less than 2.0 mg/dL. RENAL: Creatinine less than 2.0 mg/dL. CARDIOVASCULAR: No history of congestive heart failure with an LVEF less than 40%. PULMONARY: No chronic obstructive pulmonary disease. No other chronic pulmonary disease with PFTs less than 50% predicted for age. OTHER: IF HIV POSITIVE: Must have CD4 cell count greater than 500/mL and, No clinical manifestations of AIDS. Coagulation parameters no greater than 1-2 seconds within the upper limit of normal. No evidence of severe peripheral vascular disease. No history of claudication or other ischemic vascular disease. Not pregnant or nursing.
Facility Information:
Facility Name
National Cancer Institute (NCI)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
7799030
Citation
Thom AK, Alexander HR, Andrich MP, Barker WC, Rosenberg SA, Fraker DL. Cytokine levels and systemic toxicity in patients undergoing isolated limb perfusion with high-dose tumor necrosis factor, interferon gamma, and melphalan. J Clin Oncol. 1995 Jan;13(1):264-73. doi: 10.1200/JCO.1995.13.1.264.
Results Reference
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PubMed Identifier
8914206
Citation
Alexander HR Jr, Fraker DL, Bartlett DL. Isolated limb perfusion for malignant melanoma. Semin Surg Oncol. 1996 Nov-Dec;12(6):416-28. doi: 10.1002/(SICI)1098-2388(199611/12)12:63.0.CO;2-D.
Results Reference
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Pilot Study of a Double Isolation Perfusion Schedule Using Melphalan Alone for Intransit Melanoma or Unresectable Sarcoma of the Extremity

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