A Study of Pembrolizumab and Cryoablation in People With Mesothelioma

NCT05071014 | Completed Phase 1 FDA Drug

• 1 other identifier: 21-342
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 7

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.

Conditions

Lung Cancer; Unresectable Mesothelioma

Keywords

Pembrolizumab; Cryoablation; 21-342

Outcome Measures

Primary Outcomes (1)

• number of patients with an adverse event (AE) defined as any grade 3 or higher non-hematologic toxicity

  Adverse event severity is graded per NCI CTCAE v5.0.

  within 12 weeks of cryoablation

Study Arms (1)

pembrolizumab followed by cryoablation

EXPERIMENTAL

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. Treatment beyond progression at discretion of the treating physician and Study PI. There will be a research biopsy within 1 week of cycle 5 start and an optional biopsy at end of treatment and/or progression of disease.

Drug: Pembrolizumab; Procedure: Image-guided cryoablation

Interventions

Pembrolizumab DRUG

Pembrolizumab: 200mg/dose delivered by IV infusion

pembrolizumab followed by cryoablation

Image-guided cryoablation PROCEDURE

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.

pembrolizumab followed by cryoablation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (Limited protocol activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All protocol activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited protocol activities)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lung Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Michael Offin, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: September 27, 2021
• First Posted: October 7, 2021
• Study Start: September 24, 2021
• Primary Completion: December 18, 2023
• Study Completion: December 18, 2023
• Last Updated: December 20, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share

Locations

US (7)