Isolated Limb Perfusion of Melphalan for Melanoma and Sarcoma Treatment

NCT01920516 | Unknown DMC

• 2 other identifiers: ILI01ILI100513
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Melanoma

Keywords

Isolated limb infusion; Melphalan; Limb Melanoma; Tumor response

Outcome Measures

Primary Outcomes (1)

• Tumor response

  Response must be assessed by repeating the following examinations, at Day 30, Day 90 and Day 120 after start of treatment: Chest-abdomen CAT scan with and without contrast medium (refer to Section 4). Evaluation will be based on RECIST criteria \[18-22 \] cancer markers (CEA, CA 19.9)

  12 months

Secondary Outcomes (3)

• survival rate

  12 months

• time to progression

  12 months

• number of adverse events

  4 months

Study Arms (1)

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.

Drug: Melphalan

Interventions

Melphalan DRUG

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

Also known as: Alkeran

Melphalan

Eligibility Criteria

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

Study Population

primary care clinic

You may qualify if:

• Histologically proven primary or recurrent, regional melanoma or soft tissue sarcoma that is not amenable to surgical resection
• 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
• Bidimensionally measurable disease in the extremity
• Patients with disease beyond the limb are eligible if their extremity disease requires palliative treatment in the judgment of their physician
• Age: more than 18
• Karnofsky 70-100%
• Life expectancy: At least 6 months
• Hematopoietic: WBC at least 3,000/mm\^3
• Renal: Creatinine less than 2.0 mg/dL
• At least 4 weeks since prior antitumor therapy and recovered
• At least 2 weeks since prior antibiotics

You may not qualify if:

• Signs or symptoms of vascular insufficiency (no history of claudication or other ischemic peripheral vascular disease)
• pregnant or nursing
• other concurrent serious illness
• severe diabetes
• prior extremity complications due to diabetes

Sponsors & Collaborators

• International Group of Endovascular Oncology: lead

Study Sites (1)

Azienda Ospedaliera Ospedali Riuniti Marche Nord, Presidio Ospedaliero San Salvatore

Pesaro, PU, 61122, Italy

RECRUITING

Related Publications (7)

• 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.

  PMID: 19454513 RESULT

• 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.

  PMID: 17203752 RESULT

• 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.

  PMID: 12569285 RESULT

• 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.

  PMID: 11869699 RESULT

• 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.

  PMID: 34253376 DERIVED

• 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.

  PMID: 32204733 DERIVED

• 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.

  PMID: 28810925 DERIVED

Related Links

• International group of endovascular oncology (IGEVO) website

MeSH Terms

Conditions

Melanoma

Interventions

Melphalan

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

Study Officials

• Giammaria Fiorentini, MD

  International Group of Endovascular Oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Donatella Sarti, PhD

CONTACT

+39072136; igevo.datamanager@libero.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: August 6, 2013
• First Posted: August 12, 2013
• Study Start: July 1, 2013
• Primary Completion: June 1, 2019
• Study Completion: July 1, 2020
• Last Updated: February 27, 2019

Record last verified: 2019-02

Locations

IT (1)