- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01920516
Isolated Limb Perfusion of Melphalan for Melanoma and Sarcoma Treatment (ILI)
Prospective Observational Study on Isolated Limb Perfusion of Melphalan in Treating Patients With Metastasis or Recidivism of Limb Melanoma or Sarcoma That Are Not Operable
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.
Study Overview
Detailed Description
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.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Donatella Sarti, PhD
- Phone Number: 4018 +39072136
- Email: igevo.datamanager@libero.it
Study Locations
-
-
PU
-
Pesaro, PU, Italy, 61122
- Recruiting
- Azienda Ospedaliera Ospedali Riuniti Marche Nord, Presidio Ospedaliero San Salvatore
-
Principal Investigator:
- Giammaria Fiorentini, MD
-
Contact:
- Giammaria Fiorentini, MD
- Phone Number: 4124 +39072136
- Email: giammaria.fiorentini@ospedalimarchenord.it
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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 1mg/kgr is rapidly infused into the isolated limb via the arterial catheter after the inflation of venous baloon catheter.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tumor response
Time Frame: 12 months
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
survival rate
Time Frame: 12 months
|
percentage of patients alive
|
12 months
|
time to progression
Time Frame: 12 months
|
time from treatment start to progression
|
12 months
|
number of adverse events
Time Frame: 4 months
|
number of adverse events
|
4 months
|
Collaborators and Investigators
Investigators
- Principal Investigator: Giammaria Fiorentini, MD, International Group of Endovascular Oncology
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Melphalan
Other Study ID Numbers
- ILI01
- ILI100513 (Other Identifier: IGEVO)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Metastatic Melanoma
-
Mohammed M MilhemGenentech, Inc.TerminatedMelanoma | Metastatic Melanoma | BRAF-mutated Metastatic Melanoma | V600EBRAF-mutated Metastatic MelanomaUnited States
-
Delcath Systems Inc.Active, not recruitingMetastatic Uveal Melanoma | Metastatic Ocular MelanomaUnited States
-
National Cancer Institute (NCI)TerminatedMetastatic Uveal Melanoma | Metastatic Ocular MelanomaUnited States
-
MorphotekTerminatedMelanoma | Metastatic Melanoma | Advanced Melanoma | Malignant Metastatic MelanomaUnited States
-
Mayo ClinicNational Cancer Institute (NCI)Active, not recruitingMetastatic Melanoma | Metastatic Uveal Melanoma | Unresectable Melanoma | Clinical Stage III Cutaneous Melanoma AJCC v8 | Pathologic Stage IIIB Cutaneous Melanoma AJCC v8 | Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 | Pathologic Stage IIID Cutaneous Melanoma AJCC v8 | Pathologic Stage III Cutaneous... and other conditionsUnited States
-
GlaxoSmithKlineWithdrawnCancer | Metastatic Uveal Melanoma | GNA11 Mutation-positive Metastatic Melanoma | GNAQ Mutation-positive Metastatic Melanoma
-
Elizabeth DavisBristol-Myers SquibbTerminatedMetastatic Melanoma | Advanced Melanoma | Metastatic Melanoma Stratified by MHC-II ExpressionUnited States
-
Fred Hutchinson Cancer CenterAmazon.com Services LLCRecruitingAnatomic Stage IV Breast Cancer AJCC v8 | Prognostic Stage IV Breast Cancer AJCC v8 | Metastatic Cutaneous Melanoma | Unresectable Cutaneous Melanoma | Clinical Stage III Cutaneous Melanoma AJCC v8 | Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 | Pathologic Stage IIID Cutaneous Melanoma AJCC... and other conditionsUnited States
-
Provectus Biopharmaceuticals, Inc.Active, not recruitingMetastatic Colorectal Cancer | Hepatocellular Carcinoma | Metastatic Lung Cancer | Metastatic Breast Cancer | Metastatic Melanoma | Metastatic Uveal Melanoma | Metastatic Pancreatic Cancer | Metastatic Colon Cancer | Metastatic Ocular Melanoma | Cancer Metastatic to the LiverUnited States
-
National Cancer Institute (NCI)Active, not recruitingMetastatic Cutaneous Melanoma | Clinical Stage III Cutaneous Melanoma AJCC v8 | Recurrent Cutaneous Melanoma | Clinical Stage IV Cutaneous Melanoma AJCC v8 | Recurrent Mucosal Melanoma | Metastatic Mucosal Melanoma | Non-Cutaneous Melanoma | Metastatic Non-Cutaneous Melanoma | Recurrent Non-Cutaneous...United States, Canada, Ireland
Clinical Trials on Melphalan
-
Hadassah Medical OrganizationUnknown
-
Uppsala UniversityDalarna County Council, Sweden; Uppsala County Council, SwedenNot yet recruitingMyeloma Multiple
-
University of California, San FranciscoTerminatedMultiple Myeloma | Patient ParticipationUnited States
-
Delcath Systems Inc.WithdrawnHepatocellular Carcinoma (HCC)United States
-
Duke UniversityCompletedLymphoma | Leukemia | Ovarian Cancer | Brain and Central Nervous System Tumors | Extragonadal Germ Cell TumorUnited States
-
Hadassah Medical OrganizationTerminated
-
Delcath Systems Inc.Active, not recruitingBile Duct Cancer | Intrahepatic CholangiocarcinomaUnited States
-
University of ArizonaCompletedHematologic Neoplasms | Multiple Myeloma | Myelofibrosis | Anemia, Aplastic | Hemoglobinuria, ParoxysmalUnited States
-
Sidney Kimmel Comprehensive Cancer Center at Johns...TerminatedRetinoblastomaUnited States
-
Adherex Technologies, Inc.CompletedNeoplasmsUnited States