Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Melphalan

Ipilimumab

Dactinomycin

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

This is a single-institution phase II trial with a primary outcome of progression free survival (PFS).

Isolated limb infusion ((ILI) with Melphalan and Dactinomycin- MSKCC operating room. Ipilimumab- IV administration in outpatient chemotherapy clinic. Induction therapy with Ipilimumab will start 1-3 weeks after ILI in the standard dose of 10mg/kg every 3 weeks for a total of 4 doses. Patients will then receive chronic therapy every 3 months. Patients will be followed every 3 months for 2 years.

Ipilimumab, Melphalan and Dactinomycin

Charlotte Ariyan, MD,PhD

The purpose of this study is to see the effect of adding a systemic study drug, Ipilimumab, to two standard chemotherapy drugs, Melphalan and Dactinomycin. The study drug Ipilimumab is an antibody to a normal protein found in the body, CTLA-4. This protein normally allows the immune system (the body's natural defense system that helps fight infections) uses to quiet an immune response. The study drug works by blocking this protein and allowing the immune system to become more active. This study will investigate the effects, of combining ILI (using two standard drugs to treat melanoma, Melphalan and Dactinomycin), with the study drug, Ipilimumab on advanced Melanoma cancer.

Addition of Ipilimumab (MDX-010) To Isolated Limb Infusion (ILI) With Standard Melphalan and Dactinomycin In The Treatment of Advanced Unresectable Melanoma of The Extremity

A Phase II Trial of The Addition of Ipilimumab (MDX-010) To Isolated Limb Infusion (ILI) With Standard Melphalan and Dactinomycin In The Treatment of Advanced Unresectable Melanoma of The Extremity

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Progression free survival, from time of ILI, will be determined by measuring the index lesions, non-index lesions, and new lesions as described below. Patients with deep lesions will have repeat CT Scan evaluation to quantitate the lesions.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Summaries of antibody response, comparison of pretreatment with post-ipilimumab and end of treatment will be assessed for percent of CD4, CD8, and CD68 positive cells

Bristol-Myers Squibb

Memorial Sloan Kettering Cancer Center

Ipilimumab, Melphalan and Dactinomycin: Isolated limb infusion ((ILI) with Melphalan and Dactinomycin- MSKCC operating room. Ipilimumab- IV administration in outpatient chemotherapy clinic. Induction therapy with Ipilimumab will start 1-3 weeks after ILI in the standard dose of 10mg/kg every 3 weeks for a total of 4 doses. Patients will then receive chronic therapy every 3 months. Patients will be followed every 3 months for 2 years.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Charlotte Ariyan, MD

Progression Free Survival at One Year.

Toxicity of Additional Ipilimumab Will be Evaluated for All Treated Patients Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0

To Determine Response Rates of Combination Therapy. Tumor Assessment Will be Measured by the Immune Related Response Criteria (irRC).

Pretreatment CD4

Posttreatment CD4

Pretreatment CD8

Posttreatment CD8

Pretreatment CD68

Posttreatment CD68

To Define the Immunologic Events and Signatures at the Tumor Site and in the Periphery That Corresponds to Response to Ipilimumab.

Overall Study

Sarcoma

Histiocytoma, Malignant Fibrous

Sarcoma, Alveolar Soft Part

Histiocytoma

Neoplasms, Connective and Soft Tissue

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Undifferentiated Pleomorphic Sarcoma

Alveolar Soft Part Sarcoma

Central Nervous System Depressants

Antiemetics

Gastrointestinal Agents

Emetics

Anesthetics

Pembrolizumab

Advanced/metastatic extremity sarcoma eligible for pembrolizumab and isolated limb infusion (ILI)

ILI will be performed within 18 days of initiation of pembrolizumab. ILI (infusion of melphalan and dactinomycin into the affected limb via arterial catheter) will be performed in the interventional radiology suite under anesthesia. In pediatric patients, the pediatric pharmacist w ill be consulted prior to the procedure, and an appropriate prophylactic anti-emetic therapy and dose will be selected for the individual patient.

Isolated Limb Infusion

Pembrolizumab at a dose of 200 mg will be administered intravenously on Day 1 and every 3 weeks(+/= 3 days) thereafter. In adolescent patients, the dosing of pembrolizumab w ill be 2 mg/kg up to a maximum of 200 mg.

infusion of melphalan and dactinomycin

Edmund Bartlett, MD

Charlotte Ariyan, MD, PhD

Edmund Barlett, MD

The purpose of this study is to find out whether giving the study drug pembrolizumab in combination with the chemotherapy drugs melphalan and dactinomycin, delivered directly to the affected arm or leg using a technique called isolated limb infusion (ILI), is a safe treatment that can delay the time before your disease gets worse (progresses).

A Study of Pembrolizumab Plus Local Chemotherapy Using Isolated Limb Infusion (ILI) for Patients With Sarcoma in the Arm or Leg

A Phase II Study of Concurrent Systemic Pembrolizumab and Isolated Limb Infusion (ILI) With Melphalan and Dactinomycin for Patients With Locally Advanced or Metastatic Extremity Sarcoma

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Progression free survival at 6 months by RECIST 1.1 among all participants treated with the combination of ILI using melphalan and dactinomycin plus pembrolizumab

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Addition of Ipilimumab (MDX-010) To Isolated Limb Infusion (ILI) With Standard Melphalan and Dactinomycin In The Treatment of Advanced Unresectable Melanoma of The Extremity	NCT01323517	Melanoma	Ipilimumab, Mel...	18 Years -	Memorial Sloan Kettering Cancer Center
A Study of Pembrolizumab Plus Local Chemotherapy Using Isolated Limb Infusion (ILI) for Patients With Sarcoma in the Arm or Leg	NCT04332874	Sarcoma Myxofibrosarcom... Undifferentiate... Alveolar Soft P...	Isolated Limb I... Pembrolizumab infusion of mel...	12 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for isolated limb infusion