A Study of Pembrolizumab and Cryoablation in People With Mesothelioma

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05071014

Collaborator

(none)

Enrollment

Locations

Arm

35.3

Anticipated Duration (Months)

1.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The researchers are doing this study to find out whether the combination of pembrolizumab and cryoablation is a safe treatment that causes few or mild side effects in people with mesothelioma. The researchers will also look at whether the combination of pembrolizumab and cryoablation is effective against participants' cancer.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer Unresectable Mesothelioma	Drug: Pembrolizumab Procedure: Image-guided cryoablation	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This clinical trial will be designed as a single-arm, single-institution study.This clinical trial will be designed as a single-arm, single-institution study.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study of Pembrolizumab Plus Cryoablation in Patients With Unresectable Mesotheliomas

Actual Study Start Date :

Sep 24, 2021

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: pembrolizumab followed by cryoablation The treatment will consist of 1 cycle of pembrolizumab (200mg/flat dose) intravenously followed by cryoablation of an ablation index lesion 1-7 days prior to the start of cycle 2. Pembrolizumab will be continued for up to 24 months, until disease progression, or intolerable toxicity.	Drug: Pembrolizumab Pembrolizumab: 200mg/dose delivered by IV infusion Procedure: Image-guided cryoablation Cryoablation will be used to treat a designated lesion with preference given to a lesion that is symptomatic or at risk of causing symptoms. Per institutional standards, complete ablation of the lesion will be attempted.

Arm

Intervention/Treatment

Experimental: pembrolizumab followed by cryoablation

The treatment will consist of 1 cycle of pembrolizumab (200mg/flat dose) intravenously followed by cryoablation of an ablation index lesion 1-7 days prior to the start of cycle 2. Pembrolizumab will be continued for up to 24 months, until disease progression, or intolerable toxicity.

Drug: Pembrolizumab

Pembrolizumab: 200mg/dose delivered by IV infusion

Procedure: Image-guided cryoablation

Cryoablation will be used to treat a designated lesion with preference given to a lesion that is symptomatic or at risk of causing symptoms. Per institutional standards, complete ablation of the lesion will be attempted.

Outcome Measures

Primary Outcome Measures

number of patients with an adverse event (AE) defined as any grade 3 or higher non-hematologic toxicity [within 12 weeks of cryoablation]
Adverse event severity is graded per NCI CTCAE v5.0.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient willing and able to provide written informed consent for the trial
Patient age ≥ 18 at time of consent
Unresectable mesothelioma
Histologically or cytologically confirmed unresectable mesothelioma (pleural or peritoneal) as assessed by dedicated collaborators from the Departments of Pathology and Surgery.
At least one prior line of systemic therapy. Prior immunotherapy (as defined as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)) is allowed if it did not contain pembrolizumab and was not the most recent therapy, unless last treated ≥ 1 year from trial enrollment
Multifocal disease with at least one mRECIST v1.1 evaluable lesion medically safe/feasible for palliative cryoablation, as determined by the treating Interventional Radiologist, and at least one other mRECIST v1.1 measurable lesion to be monitored that will not undergo cryoablation
Agree to undergo research biopsy of the ablated lesion ± non-ablated lesion at the time of cryoablation and prior to cycle 5 if deemed medically safe and feasible
Informed consent to 12-245 and 06-107
Karnofsky Performance Score (KPS) ≥ 70%
Adequate organ function defined as:
Absolute Neutrophil Count ≥ 1.5K/mcL
Platelet count ≥ 100K/mcL
Adequate renal function as defined as Creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance ≥ 45ml/min (as calculated by Cockcroft-Gault Formula)
Hemoglobin ≥ 9g/dL (prior transfusion permitted if not within 7 days or enrollment )
Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range
AST and ALT levels ≤ 3.0 × ULN or AST
If the patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
If of childbearing potential, must be willing to use highly effective mode of contraception for at least one month prior, during, and for 2 months after the end of active therapy

Exclusion Criteria:

Currently participating and receiving another study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
Continuous supplemental oxygen use
Active autoimmune disease that might deteriorate when receiving an immuno- stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
Known prior severe hypersensitivity to pembrolizumab or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3)
Patient who rapidly progressed on prior immunotherapy, as determined by the treating physician or Primary Investigator, are not eligible
Prior cytotoxic/immunologic systemic therapy within 4 weeks prior to study Day 1 or has not recovered (i.e., ≥ Grade 1 at baseline) from adverse events due to a previously administered agent (excluding Grade 2 neuropathy)
Comorbidities or prior conditions:
Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Prior organ transplantation including allogenic stem-cell transplantation
Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, early stage prostate cancer, or in situ cervical cancer after definitive treatment
Known history of HIV or known acquired immunodeficiency syndrome.
Active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection at screening
Evidence of interstitial lung disease or active, non-infectious pneumonitis.
Clinically significant (i.e., active) cardiovascular disease as determined by anesthesiology and/or Interventional Radiology which would preclude the safe execution of cryoablation
Concomitant use of the following medications
Any investigational anticancer therapy.
Any concurrent chemotherapy, immunotherapy, or biologic therapy. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable.
Systemic anticoagulation which cannot safely be held for cryoablation/biopsies; length of anticoagulation pause will be determined by Interventional Radiology as per standard of care practices.
Immunosuppressive medications including, but not limited to systemic corticosteroids (>10 mg/day prednisone or equivalent), methotrexate, azathioprine, and tumor necrosis factor alpha (TNF-α) blockers. Use of steroids for contrast allergies is acceptable. In addition, use of inhaled and intranasal corticosteroids is permitted.
Pregnant women or women who are breastfeeding or of childbearing potential and not using a highly effective method of birth control for at least one month prior to enrollment. If the risk of contraception exists, male and female subjects must use highly effective contraception throughout the study and for at least 60 days after last pembrolizumab treatment.
Highly effective contraception includes either 2 barrier methods (diaphragm, condom by the partner, copper intrauterine device, sponge, or spermicide), or 1 barrier method and 1 hormonal method (any oral, subcutaneous, intrauterine, or intramuscular registered and marketed contraceptive agent that contains an estrogen and/or a progesterone agent).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey	United States	07920
2	Memorial 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 Commack (Limited protocol activities)	Commack	New York	United States	11725
5	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center (All protocol activities)	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau (Limited protocol activities)	Uniondale	New York	United States	11553