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

Brief Title

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

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

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).
    


Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Progression free survival


Condition

Sarcoma

Intervention

Isolated Limb Infusion

Study Arms / Comparison Groups

 Participants with Sarcoma
Description:  Advanced/metastatic extremity sarcoma eligible for pembrolizumab and isolated limb infusion (ILI)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Procedure

Estimated Enrollment

30

Start Date

April 1, 2020

Completion Date

April 1, 2023

Primary Completion Date

April 1, 2023

Eligibility 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 (currently: myxofibrosarcoma,
             undifferentiated pleomorphic sarcoma, and alveolar soft part sarcoma)

          -  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 /= 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 ULN Aspartate
                  aminotransferase (AST) /= 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)  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 					

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Edmund Bartlett, MD, 212-639-2448, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04332874

Organization ID

20-104


Responsible Party

Sponsor

Study Sponsor

Memorial Sloan Kettering Cancer Center


Study Sponsor

Edmund Bartlett, MD, Principal Investigator, Memorial Sloan Kettering Cancer Center


Verification Date

April 2020