Isolated Limb Perfusion of Melphalan for Melanoma and Sarcoma Treatment

NCT ID: NCT01920516

Last Updated: 2019-02-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

40 participants

Study Classification

OBSERVATIONAL

Study Start Date

2013-07-31

Study Completion Date

2020-07-31

Brief Summary

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In-transit metastases occur in approximately 3% of melanoma patients, can be very symptomatic and the survival in this group may be prolonged. In-transit melanoma metastases are often confined to a limb. In this circumstance, treatment by isolated limb perfusion or isolated limb infusion can be a remarkably effective regional treatment option. Isolated limb infusion (ILI) was introduced in 1992 and is a technique used to deliver regional chemotherapy to treat advanced melanoma confined to a limb. Regional chemotherapy with melphalan delivered by isolated limb perfusion (ILP) or ILI are effective treatment options for in-transit melanoma and are generally well tolerated.

ILI is a less invasive and simpler alternative to ILP. Complete response rates are 45- 69% for ILP and 23-44% for ILI. The limb is often warmed to lower temperatures in ILI compared to ILP and the limb becomes progressively more hypoxic and acidotic during ILI, each of these parameters potentially having an effect on outcome. ILP \& ILI are used primarily as palliative options when excision of in-transit metastases is unfeasible but can be used as an adjunctive procedure to surgery, for other tumour types such as merkel cell carcinoma, and can be repeated if indicated. For ILI correction of melphalan dose for ideal body weight has been shown to substantially decrease the rates of severe local toxicity while maintaining complete response rates, but overall response rate is reduced.

Response to ILI, moreover, is different in upper and lower limbs. ILI for Upper limbs disease is associated with similar complete response rates but lower toxicity than ILI for Lower limbs E disease and with different physiologic sequelae despite comparable methods. The Upper limbs appears relatively resistant to toxic effects of melphalan-based ILI as currently performed, which suggests a potential for further optimization of drug dosing for Upper limbs ILI.

Regional therapy is an excellent therapeutic modality for disease limited to a limb and furthermore serves as an excellent model for scientific investigation, both clinical and translational. In this study we want to collect data on isolated limb infusion of chemotherapy to monitor efficacy and tolerability in patients with melanoma metastases of the arm or leg that cannot be removed by surgery.

Detailed Description

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This is an observational study and the treatment is related to the experiences and economical availability of each center.

Study Design: Prospective observational study . Primary objective: To collect data on tumor response and progression free survival after administration of melphalan.

Secondary objectives: To collect data on survival rate, time to progression, morbidity tolerability of treatment, number of treatment required to achieve objective response and improvement of quality of life (Edmonton questionnaire)

Treatment under observation :

Patients undergo fluoroscopic placement of angiographic arterial and venous catheters into the appropriate extremity in order to infuse the drug (artery) and to stop the out flow (venous with balloon catheter). Melphalan 1mg/kgr is rapidly infused into the isolated limb via the arterial catheter after the inflation of venous balloon catheter. Then the circulation of the limb is blocked with a pneumatic cuff at the root of the limb . Patients with little or no response at 8 weeks may receive up to 2 additional treatments at the discretion of the treating physician.

Patients are followed at 1-2 weeks, 3-4 weeks, 6-8 weeks, and then every 3-6 months thereafter as deemed necessary by the treating physician.

Day -1 Melphalan 1mg/ Kgr has been prepared at Pharmacy.

Day 0: prehydration, antibiotic prophylaxis and setting up of a therapeutic scheme appropriate for analgesic prophylaxis (3-day duration) as previously reported (25)

Day +1:

Upon admittance to the radiology room, 1 vial of tropisetron (diluted in 100ml of physiological solution) administered by slow drip.

During infusion of the Melphalan into the artery, 1 vial of morphine hydrochloride diluted in 100 ml i.v. to be repeated one hour after the procedure and if necessary also after 6 hours.

Tropisetron i.v. if needed. Intra-arterial premedication with 1 vial of verapamil diluted in 4 ml of normal saline solution followed by 4 ml of lidocaine.

Intra femoral infusion of Melphalan Second ILI treatment could be repeated at side effects recovery ( following oncologist ' s planning of cure).

Day +30: The above procedure is repeated.

Day +90: In case of response, a third administration following the above procedures will be repeated.

Evaluation of response:

Response must be assessed by repeating the following examinations at Day 30, Day 90 and Day 120 after start of treatment:

Limb-Chest-abdomen CAT scan with and without contrast medium (refer to Section 4). Evaluation will be based on Response Evaluation Criteria in Solid Tumors (RECIST ) criteria \[20-24 \] cancer markers (CEA, cancer antigen (CA) 19.9)

Assessment of quality of life The Edmonton Symptom Assessment System (ESAS) is used to monitor health conditions and quality of life.

Assessment of quality of life is performed during the baseline visit and at Day 30, Day 60 and Day 120 from start of treatment.

Conditions

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Metastatic Melanoma

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Melphalan

Day +1:

Intra femoral infusion of Melphalan at the dosage 1mg/ Kg

Intra femoral infusion of Melphalan Second ILI treatment can be repeated at side effects recovery ( following oncologist ' s planning of cure).

Day +30: The above procedure is repeated.

Day +90: In case of response, a third administration following the above procedures will be repeated.

Melphalan

Intervention Type DRUG

Melphalan 1mg/kgr is rapidly infused into the isolated limb via the arterial catheter after the inflation of venous baloon catheter.

Interventions

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Melphalan

Melphalan 1mg/kgr is rapidly infused into the isolated limb via the arterial catheter after the inflation of venous baloon catheter.

Intervention Type DRUG

Other Intervention Names

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Alkeran

Eligibility Criteria

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Inclusion Criteria

1. Histologically proven primary or recurrent, regional melanoma or soft tissue sarcoma that is not amenable to surgical resection
2. Majority (greater than 95%) of disease must be distal to the apex of the femoral triangle in the lower limb and the deltoid insertion in the upper limb
3. Bidimensionally measurable disease in the extremity
4. Patients with disease beyond the limb are eligible if their extremity disease requires palliative treatment in the judgment of their physician
5. Age: more than 18
6. Karnofsky 70-100%
7. Life expectancy: At least 6 months
8. Hematopoietic: WBC at least 3,000/mm\^3
9. Renal: Creatinine less than 2.0 mg/dL
10. At least 4 weeks since prior antitumor therapy and recovered
11. At least 2 weeks since prior antibiotics

Exclusion Criteria

1. Signs or symptoms of vascular insufficiency (no history of claudication or other ischemic peripheral vascular disease)
2. pregnant or nursing
3. other concurrent serious illness
4. severe diabetes
5. prior extremity complications due to diabetes
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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International Group of Endovascular Oncology

OTHER

Sponsor Role lead

Responsible Party

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Giammaria Fiorentini

Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Giammaria Fiorentini, MD

Role: PRINCIPAL_INVESTIGATOR

International Group of Endovascular Oncology

Locations

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Azienda Ospedaliera Ospedali Riuniti Marche Nord, Presidio Ospedaliero San Salvatore

Pesaro, PU, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Donatella Sarti, PhD

Role: CONTACT

+39072136 ext. 4018

Facility Contacts

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Giammaria Fiorentini, MD

Role: primary

+39072136 ext. 4124

References

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Ruscitti C, Guadagni S, Russo F, Palumbo G, Fiorentini G, Mambrini A, Cantore M, Kanavos E, Pinto A, Amicucci G. Thoracic stop-flow perfusion for refractory lymphoma: a phase I-II evaluation trial. In Vivo. 2009 May-Jun;23(3):447-57.

Reference Type RESULT
PMID: 19454513 (View on PubMed)

Guadagni S, Clementi M, Valenti M, Fiorentini G, Cantore M, Kanavos E, Amicucci G. Thoracic stop-flow perfusion in the treatment of refractory malignant pleural mesothelioma: a phase I-II evaluation/trial. In Vivo. 2006 Nov-Dec;20(6A):715-8.

Reference Type RESULT
PMID: 17203752 (View on PubMed)

Guadagni S, Santinami M, Patuzzo R, Pilati PL, Miotto D, Deraco M, Rossi CR, Fiorentini G, Di Filippo F, Valenti M, Amicucci G. Hypoxic pelvic and limb perfusion with melphalan and mitomycin C for recurrent limb melanoma: a pilot study. Melanoma Res. 2003 Feb;13(1):51-8. doi: 10.1097/00008390-200302000-00009.

Reference Type RESULT
PMID: 12569285 (View on PubMed)

Guadagni S, Russo F, Rossi CR, Pilati PL, Miotto D, Fiorentini G, Deraco M, Santinami M, Palumbo G, Valenti M, Amicucci G. Deliberate hypoxic pelvic and limb chemoperfusion in the treatment of recurrent melanoma. Am J Surg. 2002 Jan;183(1):28-36. doi: 10.1016/s0002-9610(01)00841-8.

Reference Type RESULT
PMID: 11869699 (View on PubMed)

Guadagni S, Zoras O, Fiorentini G, Masedu F, Lasithiotakis K, Sarti D, Farina AR, Mackay AR, Clementi M. A Prospective Study of Intraarterial Infusion Chemotherapy in Advanced Wild-Type BRAF Melanoma Patients. J Surg Res. 2021 Dec;268:737-747. doi: 10.1016/j.jss.2021.05.054. Epub 2021 Jul 10.

Reference Type DERIVED
PMID: 34253376 (View on PubMed)

Guadagni S, Fiorentini G, Papasotiriou I, Apostolou P, Masedu F, Sarti D, Farina AR, Mackay AR, Clementi M. Circulating tumour cell liquid biopsy in selecting therapy for recurrent cutaneous melanoma with locoregional pelvic metastases: a pilot study. BMC Res Notes. 2020 Mar 24;13(1):176. doi: 10.1186/s13104-020-05021-5.

Reference Type DERIVED
PMID: 32204733 (View on PubMed)

Guadagni S, Palumbo G, Fiorentini G, Clementi M, Marsili L, Giordano AV, Masedu F, Valenti M. Surgical versus percutaneous isolated pelvic perfusion (IPP) for advanced melanoma: comparison in terms of melphalan pharmacokinetic pelvic bio-availability. BMC Res Notes. 2017 Aug 15;10(1):411. doi: 10.1186/s13104-017-2738-y.

Reference Type DERIVED
PMID: 28810925 (View on PubMed)

Related Links

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http://igevo.jimdo.com/

International group of endovascular oncology (IGEVO) website

Other Identifiers

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ILI100513

Identifier Type: OTHER

Identifier Source: secondary_id

ILI01

Identifier Type: -

Identifier Source: org_study_id

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