RECRUITING

A Study of Pembrolizumab and Radiation Therapy in People With Mesothelioma

Conditions

Malignant Pleural Mesothelioma MPM intensity-modulated pleural radiation therapy IMPRINT Pembrolizumab 21-197 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 IMPRINT in combination with pembrolizumab is a safe treatment for people with malignant pleural mesothelioma (MPM).The highest dose of IMPRINT that causes few or mild side effects when given in combination with pembrolizumab will be found. Once the highest safe dose of IMPRINT is found, it will be tested in combination with pembrolizumab in future participants to see whether the combination may be an effective treatment for MPM.

Official Title

Phase I Dose Escalation and Local Control Study of Pembrolizumab + Intensity-Modulated Pleural Radiation Therapy (IMPRINT) for Malignant Pleural Mesothelioma

Quick Facts

Study Start:2021-08-10

Study Completion:2026-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04897022

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:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Pathologically confirmed diagnosis of malignant pleural mesothelioma * Unresectable per thoracic surgeon assessment * At least one prior line of systemic therapy. Note: Patients who were on prior immunotherapy are eligible. * ECOG 0-1 * PFTs: DLCO \>40% predicted, FEV1 \>50% predicted * Male/female participants who are at least 18 years of age on the day of signing informed consent * Disease outside the ipsilateral thorax allowed as long as it has either been treated definitively and been stable for 6 months * A male participant must agree to use a contraception as detailed in Appendix 1 of this protocol during the treatment period and for at least 30 days, corresponding to time needed to eliminate any study treatment(s) (pembrolizumab and or any active comparator/combination) plus an additional 120 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose after the last dose of study treatment and refrain from donating sperm during this period. * A female participant is eligible to participate if she is not pregnant (see Appendix 1), not breastfeeding, and at least one of the following conditions applies: 1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 1 OR 2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 1 during the treatment period and for at least 120 days (corresponding to time needed to eliminate any study treatment(s) (pembrolizumab and or any active comparator/combination) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity after the last dose of study treatment. * The participant (or legally authorized representative if applicable) provides written informed consent for the trial. * Have a ECOG performance status of 0 to 1. Evaluation of ECOG is to be performed within 30 days prior to the date of allocation. * Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 45 days prior to the start of study treatment.	* Newly diagnosed MPM * Prior thoracic radiation therapy or intrapleural therapy * Bulky disease in the fissure preventing IMPRINT * Serious infection, concurrent active malignancies, or other serious medical illness * Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137) 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 * Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. * Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Low grade malignancies not requiring active treatment are not excluded. * Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. * Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients. * Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. * Has a known history of Human Immunodeficiency Virus (HIV). * Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. * Has a known history of active TB (Bacillus Tuberculosis). * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. * Has undergone major surgery \<4 weeks from starting pembrolizumab.

Inclusion Criteria

Exclusion Criteria

* Pathologically confirmed diagnosis of malignant pleural mesothelioma
* Unresectable per thoracic surgeon assessment
* At least one prior line of systemic therapy. Note: Patients who were on prior immunotherapy are eligible.
* ECOG 0-1
* PFTs: DLCO \>40% predicted, FEV1 \>50% predicted
* Male/female participants who are at least 18 years of age on the day of signing informed consent
* Disease outside the ipsilateral thorax allowed as long as it has either been treated definitively and been stable for 6 months
* A male participant must agree to use a contraception as detailed in Appendix 1 of this protocol during the treatment period and for at least 30 days, corresponding to time needed to eliminate any study treatment(s) (pembrolizumab and or any active comparator/combination) plus an additional 120 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose after the last dose of study treatment and refrain from donating sperm during this period.
* A female participant is eligible to participate if she is not pregnant (see Appendix 1), not breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 1 OR
2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 1 during the treatment period and for at least 120 days (corresponding to time needed to eliminate any study treatment(s) (pembrolizumab and or any active comparator/combination) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity after the last dose of study treatment.
* The participant (or legally authorized representative if applicable) provides written informed consent for the trial.
* Have a ECOG performance status of 0 to 1. Evaluation of ECOG is to be performed within 30 days prior to the date of allocation.
* Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 45 days prior to the start of study treatment.

* Newly diagnosed MPM
* Prior thoracic radiation therapy or intrapleural therapy
* Bulky disease in the fissure preventing IMPRINT
* Serious infection, concurrent active malignancies, or other serious medical illness
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137) 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
* Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
* Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Low grade malignancies not requiring active treatment are not excluded.
* Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
* Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
* Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Has a known history of Human Immunodeficiency Virus (HIV).
* Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection.
* Has a known history of active TB (Bacillus Tuberculosis).
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
* Has undergone major surgery \<4 weeks from starting pembrolizumab.

Contacts and Locations

Study Contact

Charles Simone, MD

CONTACT

212-639-3716

simonec1@mskcc.org

Michael Offin, MD

CONTACT

646-608-3763

offinm@mskcc.org

Principal Investigator

Charles Simone, 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 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)

Rockville Centre, New York, 11553

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Charles Simone, 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 Date2021-08-10

Study Completion Date2026-08

Study Record Updates

Study Start Date2021-08-10

Study Completion Date2026-08

Terms related to this study

Keywords Provided by Researchers

malignant pleural mesothelioma
MPM
intensity-modulated pleural radiation therapy
IMPRINT
Pembrolizumab
21-197
Memorial Sloan Kettering Cancer Center

Additional Relevant MeSH Terms

Malignant Pleural Mesothelioma