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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04332874

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

4.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Anticipated 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 :

Apr 1, 2020

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

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. 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. Other Names: ILI Drug: Pembrolizumab 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. Drug: infusion of melphalan and dactinomycin infusion of melphalan and dactinomycin

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. 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.

Other Names:

ILI

Drug: Pembrolizumab

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.

Drug: infusion of melphalan and dactinomycin

infusion of melphalan and dactinomycin

Outcome Measures

Primary Outcome Measures

Progression free survival [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 >/= 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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memoral Sloan Kettering Basking Ridge (Limited protocol activities)	Basking Ridge	New Jersey	United States	07920
2	Memoral Sloan Kettering Monmouth (Limited protocol activities)	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Cancer Center @ Suffolk - Commack (Limited Protocol Activities)	Commack	New York	United States	11725
5	Memoral Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York	United States	11553