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

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ClinicalTrials.gov Identifier: NCT04332874
Recruitment Status : Recruiting
First Posted : April 3, 2020
Last Update Posted : January 28, 2021
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Sarcoma Myxofibrosarcoma Undifferentiated Pleomorphic Sarcoma Alveolar Soft Part Sarcoma Procedure: Isolated Limb Infusion Drug: Pembrolizumab Drug: infusion of melphalan and dactinomycin Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 1, 2020
Estimated Primary Completion Date : April 1, 2023
Estimated Study Completion Date : April 1, 2023


Arm Intervention/treatment
Experimental: Participants with Sarcoma
Advanced/metastatic extremity sarcoma eligible for pembrolizumab and isolated limb infusion (ILI)
Procedure: Isolated Limb Infusion
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.
Other Name: ILI

Drug: Pembrolizumab
Pembrolizumab at a dose of 200 mg will be administered intravenously on Day 1 and every 3 weeks(+/= 3 days) thereafter.

Drug: infusion of melphalan and dactinomycin
infusion of melphalan and dactinomycin




Primary Outcome Measures :
  1. Progression free survival [ Time Frame: 6 months ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients must fulfill all of the following criteria to be eligible for admission to the study. Any exceptions from the protocol-specific selection criteria must be approved by the Principal Investigator and/or the Institutional Review Board (IRB) before enrollment.

  • Age >/= 18 years at the time of informed consent
  • Willing and able to provide written informed consent/assent for the trial
  • Willing to comply with treatment protocol
  • Have a histologically confirmed metastatic and/or locally advanced sarcoma
  • Eligible for standard treatment with pembrolizumab
  • Eligible for an isolated limb infusion (ILI) as determined by the treating physician
  • Have undergone at least one prior line of systemic therapy (e.g. chemotherapy, immunotherapy, targeted or biological therapy) or have declined the standard of care systemic option.
  • Have measurable disease (at least one index lesion) as defined by RECIST 1.1 or by clinical measurement for superficial lesions not amenable to radiographic surveillance. Index lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to enrollment.
  • Adequate performance status: ECOG </= 2 or KPS >/= 60%
  • Adequate organ function determined within 3 weeks of treatment initiation, defined as follows:

    • Hemoglobin >/= 8.0 g/dL
    • Absolute neutrophil count >/= 1,000/mm^3 (1.0 x 10^9/L)
    • Platelet count >/= 50,000/mm^3 (50 x 10^9/L)
    • Serum bilirubin </= 1.5 x upper limit of normal (ULN) OR direct bilirubin </= ° ° ULN for a patient with total bilirubin level > 1.5 x ULN Aspartate aminotransferase (AST) </= 2.5 x ULN OR </= 5 x ULN for patients with liver metastases
    • Alanine aminotransferase (ALT) </= 2.5 x ULN OR </= 5 x ULN for patients with liver metastases
    • Alkaline phosphatase < 5 x ULN
    • Serum creatinine </= 1.5 x ULN or a measured or calculated creatinine clearance >/= 60 mL/min for a patient with creatinine levels > 1.5 x institutional ULN (Note: Creatinine clearance need not be determined if the baseline serum creatinine is within normal limits. GFR can also be used in place of creatinine or CrCl)
    • International normalized ratio (INR) or prothrombin time (PT) </= 1.5 X ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
    • Activated partial thromboplastin time (aPTT) </= 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT and PTT is within therapeutic range of intended use of anticoagulants

Creatinine clearance should be calculated per institutional standard.

For female patients of childbearing potential, negative serum pregnancy test at screening visit and within 72 h prior to the first dose of study medication.

Exclusion Criteria:

Patients who fulfil any of the following criteria are not eligible for admission to the study:

  • Have any other malignancy that requires active treatment
  • Ineligible for ILI because of underlying physical conditions (e.g. coronary artery disease with inability to tolerate anesthesia) as determined by treating physician
  • Has previously experienced hypersensitivity to pembrolizumab or any of its excipients
  • Has uncontrolled intercurrent illness including active infection requiring systemic therapy or symptomatic congestive heart failure within the past 6 months
  • Has known active central nervous system (CNS) metastases. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to study Day 1 and return to baseline of neurologic symptoms), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include sarcomatous meningitis, which is excluded regardless of clinical stability.
  • Shows evidence of clinically significant immunosuppression such as the following:

    • Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease
    • Concurrent opportunistic infection
    • Receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid doses > 10 mg/day of prednisone or equivalent within 7 days prior to enrollment. However, in the setting of non-immune mediated indications for use, chronic/active low dose steroid use may be permitted at the discretion of the principal investigator.
  • Has a known active or chronic infection with HIV if CD4 count is less than 500.
  • Has a known active infection with hepatitis B or hepatitis C
  • Has a known history of active tuberculosis infection
  • Has history or evidence of symptomatic autoimmune disease (e.g., pneumonitis, glomerulonephritis, vasculitis, or other), or history of active autoimmune disease that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in the past 2 years. Replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment for autoimmune disease.
  • For female subjects, is pregnant or breast-feeding, or planning to become pregnant
  • For male subjects, is planning to father a child within the projected duration of the trial, starting with the pre-screening or screening visit, during study treatment and through 4 months after the last dose of pembrolizumab
  • For patients of childbearing potential, is unwilling to use acceptable method(s) of effective contraception during study treatment and through 4 months after the last dose of pembrolizumab.

(Women not of childbearing potential are defined as: post-menopausal [age > 55 years with cessation of menses for 12 or more months or less than 55 years but not spontaneous menses for at least 2 years or less than 55 years and spontaneous menses within the past 1 year, but currently amenorrhoeic (e.g., spontaneous or secondary to hysterectomy), and with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved] or who have had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.)

  • Underwent prior chemotherapy, radiotherapy, biological cancer therapy, targeted small molecule therapy, or major surgery within 14 days prior to study Day 1 or has not recovered (i.e., to CTCAE </= grade 1 or at baseline) from adverse events due to previously administered therapy. Patients with </= grade 2 neuropathy and alopecia are an exception and may qualify for the study. If patients received major surgery, they must have recovered adequately prior to starting therapy.
  • Is currently participating and receiving study therapy with another investigational device or study drug or has participated in a study of an investigational agent and received study therapy or used an investigational device within 3 weeks of the first dose of treatment
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04332874


Contacts
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Contact: Edmund Bartlett, MD 212-639-2448 bartlete@mskcc.org
Contact: Charlotte Ariyan, MD, PhD 212-639-6280 ariyanc@mskcc.org

Locations
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United States, New Jersey
Memoral Sloan Kettering Basking Ridge (Limited protocol activities) Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Edmund Barlett, MD    212-639-2448      
Memoral Sloan Kettering Monmouth (Limited protocol activities) Recruiting
Middletown, New Jersey, United States, 07748
Contact: Edmund Barlett, MD    212-639-2448      
Memorial Sloan Kettering Bergen (Limited Protocol Activities) Recruiting
Montvale, New Jersey, United States, 07645
Contact: Edmund Barlett, MD    212-639-2448      
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk - Commack (Limited Protocol Activities) Recruiting
Commack, New York, United States, 11725
Contact: Edmund Barlett, MD    212-639-2448      
Memoral Sloan Kettering Westchester (Limited Protocol Activities) Recruiting
Harrison, New York, United States, 10604
Contact: Edmund Barlett, MD    212-639-2448      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Edmund Bartlett, MD    212-639-2448      
Memorial Sloan Kettering Nassau (Limited Protocol Activities) Recruiting
Uniondale, New York, United States, 11553
Contact: Edmund Barlett, MD    212-639-2448      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Edmund Bartlett, MD Memorial Sloan Kettering Cancer Center
Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04332874    
Other Study ID Numbers: 20-104
First Posted: April 3, 2020    Key Record Dates
Last Update Posted: January 28, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
Sarcoma
Myxofibrosarcoma
Undifferentiated Pleomorphic Sarcoma
Alveolar Soft Part Sarcoma
Pembrolizumab
Isolate Limb Infusion
Melphalan
Dactinomycin
Metastatic Extremity Sarcoma
Locally Advanced Sarcoma
20-104
Memorial Sloan Kettering Cancer Center
Additional relevant MeSH terms:
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Sarcoma
Sarcoma, Alveolar Soft Part
Histiocytoma, Malignant Fibrous
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Muscle Tissue
Histiocytoma
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Dactinomycin
Pembrolizumab
Melphalan
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Protein Synthesis Inhibitors
Enzyme Inhibitors
Nucleic Acid Synthesis Inhibitors