RECRUITING

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

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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).

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

Quick Facts

Study Start:2020-04-01

Study Completion:2025-04-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04332874

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Age \>/= 12 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	* 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. * 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

Inclusion Criteria

Exclusion Criteria

* Age \>/= 12 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

* 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.
* 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

Contacts and Locations

Study Contact

Edmund Bartlett, MD

CONTACT

212-639-2448

bartlete@mskcc.org

Charlotte Ariyan, MD, PhD

CONTACT

212-639-6280

ariyanc@mskcc.org

Principal Investigator

Edmund Bartlett, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Memorial Sloan Kettering Basking Ridge (Limited protocol activities)

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth (Limited protocol activities)

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Cancer Center @ Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Edmund Bartlett, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-04-01

Study Completion Date2025-04-01

Study Record Updates

Study Start Date2020-04-01

Study Completion Date2025-04-01

Terms related to this study

Keywords Provided by Researchers

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

Sarcoma
Myxofibrosarcoma
Undifferentiated Pleomorphic Sarcoma
Alveolar Soft Part Sarcoma