Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Malignant Mesothelioma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants will be diagnosed with malignant pleural mesothelioma and be deemed unresectable per thoracic surgeon assessment

Fixed dose of pembrolizumab 200mg IV q3 weeks

The starting radiation dose will consist of 400cGy x5 fractions. Doses will be escalated by 100cGy per fraction (i.e. 400cGy, 500cGy, 600cGy) for a total of 3 dose levels. The MTD will be evaluated using a modified Continuous Reassessment Method. Dose limiting toxicities (DLTs) are defined as any treatment-related non-hematologic toxicity with a CTCAE v5 Grade ≥3 or grade ≥2 pneumonitis that requires use of steroids occurring after the start of IMPRINT through the first 3 months after the last fraction.

IMPRINT

Annemarie Shepherd, MD

Michael Offin, MD

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.

A Study of Pembrolizumab and Radiation Therapy in People With Mesothelioma

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

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

The first primary objective of this study is to determine the MTD of IMPRINT among the three candidate doses: 400cGy x5 fractions, 500cGy x5 fractions and 600cGy x5 fractions. These dose levels will be evaluated using a modified Continuous Reassessment Method (CRM) starting with the lowest dose level 400cGy x5 fractions. Determined by the first 12 participants enrolled to the study.

Memorial Sloan Kettering Cancer Center

Micronutrients

Hematinics

Amino Acids

Vitamins

Carboplatin

Pemetrexed

Cisplatin

Folic Acid Antagonists

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Glutamic Acid

Folinic Acid

Folate

Vitamin B9

STEP 1: Patients undergo P/D then within 4 to 8 weeks receive pemetrexed IV over 10 minutes and cisplatin or carboplatin IV over 60 minutes on day 1. Patients may instead receive pemetrexed IV over 10 minutes and cisplatin or carboplatin IV over 60 minutes on day 1 then undergo P/D within 4 to 8 weeks after chemotherapy. The order of surgery and chemotherapy is at the discretion of the treating physician.

STEP 2: Patients receive no treatment.

STEP 1: Patients undergo P/D then within 4 to 8 weeks receive pemetrexed IV over 10 minutes and cisplatin or carboplatin IV over 60 minutes on day 1. Patients may instead receive pemetrexed IV over 10 minutes and cisplatin or carboplatin IV over 60 minutes on day 1 then undergo P/D within 4 to 8 weeks after chemotherapy. The order of surgery and chemotherapy is at the discretion of the treating physician.

STEP 2: Within 4-8 weeks from the end of Step 1 treatment, patients undergo 25-28 fractions IMRT or PBS proton therapy 5 days per week over 6 weeks.

Decortication

Intensity-Modulated Radiation Therapy

Pemetrexed Disodium

Pencil Beam Scanning

Pleurectomy

Quality-of-Life Assessment

Questionnaire Administration

Andreas Rimner, MD

This trial studies how well the addition of targeted radiation therapy to surgery and the usual chemotherapy treatment works for the treatment of stage I-IIIA malignant pleural mesothelioma. Targeted radiation therapy such as intensity-modulated radiation therapy or pencil beam scanning uses high energy rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as pemetrexed, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving targeted radiation therapy in addition to surgery and chemotherapy may work better than surgery and chemotherapy alone for the treatment of malignant pleural mesothelioma.

PRIMARY OBJECTIVE:

I. To detect an improvement in overall survival with the addition of adjuvant hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) to surgery and chemotherapy compared to surgery and chemotherapy alone.

SECONDARY OBJECTIVES:

I. To determine local failure-free survival, distant-metastases-free survival, and progression-free survival with the addition of adjuvant hemithoracic IMPRINT to surgery and chemotherapy compared to surgery and chemotherapy alone.

II. To evaluate the treatment-related toxicities in both arms per Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.

III. To detect a clinically meaningful 10-point change in global health status mean scores at 9 months after randomization with the addition of adjuvant IMPRINT as compared to surgery and chemotherapy alone.

EXPLORATORY OBJECTIVES:

I. To evaluate the degree of under-staging, concordant and upstaging between centrally-reviewed clinical staging (based on positron emission tomography \[PET\], computed tomography \[CT\] and/or magnetic resonance imaging \[MRI\]) and pathologic staging.

II. To identify immunologic and pathologic biomarkers as predictors of response and potential targets for future combination trials.

III. To determine the magnitude of radiation dose escalation to gross residual disease based on combined modality imaging and associated local control rates with dose-painting intensity-modulated radiation therapy (IMRT).

IV. To determine the rate of R0/R1 and R2 resections, and type of procedures (extended pleurectomy/decortication \[P/D\], P/D and partial pleurectomy).

V. To evaluate the trajectory of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-Q30) and lung cancer specific module (LC13) symptoms in patients treated with IMPRINT by comparing the proportion of patients who respond with "quite a bit" or "very much" LC13 symptoms at 9-12 months post-randomization compared to at 3 months post-randomization.

VI. To evaluate changes in health-related quality of life, functional domains, and symptoms over time with the addition of adjuvant IMPRINT as compared to surgery and chemotherapy alone.

OUTLINE:

STEP 1: Patients undergo P/D then within 4 to 8 weeks receive pemetrexed intravenously (IV) over 10 minutes and cisplatin or carboplatin IV over 60 minutes on day 1. Patients may instead receive pemetrexed IV over 10 minutes and cisplatin or carboplatin IV over 60 minutes on day 1 then undergo P/D within 4 to 8 weeks after chemotherapy. The order of surgery and chemotherapy is at the discretion of the treating physician.

STEP 2: Within 4 to 8 weeks from the end of Step 1 treatment, patients are randomized to 1 of 2 arms.

ARM I: Patients receive no treatment.

ARM II: Patients undergo 25-28 fractions IMRT or pencil beam scanning (PBS) proton therapy 5 days per week over 6 weeks.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years.

Testing the Addition of Targeted Radiation Therapy to Surgery and the Usual Chemotherapy Treatment (Pemetrexed and Cisplatin [or Carboplatin]) for Stage I-IIIA Malignant Pleural Mesothelioma

Phase III Randomized Trial of Pleurectomy/Decortication Plus Systemic Therapy With or Without Adjuvant Hemithoracic Intensity-Modulated Pleural Radiation Therapy (IMPRINT) for Malignant Pleural Mesothelioma (MPM)

For each subject, the centrally-reviewed clinical staging (based on positron emission tomography, computed tomography and/or magnetic resonance imaging) will be compared with pathologic staging to determine whether it is under-staging (clinical staging is more extensive than pathologic staging), concordant (clinical staging is same as pathologic staging), or upstaging (clinical staging is less extensive than pathologic staging). The proportion of under-staging, concordant and upstaging, along with the associated 95% confidence intervals, will be reported.

Gross residual disease and local failure will be analyzed as competing risk data (death without gross residual disease or death without local failure as the respective competing event). Association between radiation dose to gross residual disease and local failure will be evaluated similarly in multivariable analyses using Fine-Gray regression model.

Proportions of R0/R1 and R2 resections, by type of procedures (extended pleurectomy/decortication (P/D), P/D and partial pleurectomy), along with 95% confidence intervals, will be reported.

Will compare the distributions of OS between treatment arms using a one-sided stratified log-rank test (using stratification factors as strata). The rates at various timepoints (e.g., every 6 months after randomization) and medians of OS for each arm will be estimated using the Kaplan-Meier method. The associated 90% confidence interval (CI) will be calculated using Greenwood?s formula and based on a log-log transformation applied on the survival function. Hazard ratios will be estimated using a stratified Cox regression model.

Will compare the distributions of LFFS between treatment arms using a one-sided stratified log-rank test (using stratification factors as strata). The rates at various timepoints (e.g., every 6 months after randomization) and medians of LFFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% CI will be calculated using Greenwood?s formula and based on a log-log transformation applied on the survival function. Hazard ratios for LFFS will be estimated using a stratified Cox regression model.

Will compare the distributions of DMFS between treatment arms using a one-sided stratified log-rank test (using stratification factors as strata). The rates at various timepoints (e.g., every 6 months after randomization) and medians of DMFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% CI will be calculated using Greenwood?s formula and based on a log-log transformation applied on the survival function. Hazard ratios for PFS will be estimated using a stratified Cox regression model.

Will compare the distributions of PFS between treatment arms using a one-sided stratified log-rank test (using stratification factors as strata). The rates at various timepoints (e.g., every 6 months after randomization) and medians of PFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% CI will be calculated using Greenwood?s formula and based on a log-log transformation applied on the survival function. Hazard ratios for PFS will be estimated using a stratified Cox regression model.

Adverse events (AEs) will be graded with Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. All adverse events, adverse events leading to withdrawal, interruption or modification of protocol treatment, grade \>= 3 adverse events, and serious adverse events will be summarized. Deaths and cause of death will be summarized. The rate of treatment-related adverse events will be reported with the frequency and severity (e.g., type, grade, and attribution) by arm.

Measured by European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaires.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Pembrolizumab and Radiation Therapy in People With Mesothelioma	NCT04897022	Malignant Pleur...	Pembrolizumab IMPRINT	18 Years -	Memorial Sloan Kettering Cancer Center
Testing the Addition of Targeted Radiation Therapy to Surgery and the Usual Chemotherapy Treatment (Pemetrexed and Cisplatin [or Carboplatin]) for Stage I-IIIA Malignant Pleural Mesothelioma	NCT04158141	Pleural Biphasi... Pleural Epithel... Stage I Pleural... Stage IA Pleura... Stage IB Pleura... Stage II Pleura... Stage IIIA Pleu...	Carboplatin Cisplatin Decortication Intensity-Modul... Pemetrexed Pemetrexed Diso... Pencil Beam Sca... Pleurectomy Quality-of-Life... Questionnaire A...	18 Years - 80 Years	NRG Oncology
A Study of Pembrolizumab and Radiation Therapy in People With Mesothelioma	NCT04897022	Malignant Pleur...	Pembrolizumab IMPRINT	18 Years -	Memorial Sloan Kettering Cancer Center
A Study of Pembrolizumab and Radiation Therapy in People With Mesothelioma	NCT04897022	Malignant Pleur...	Pembrolizumab IMPRINT	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for imprint

Every month we try and update this database with for imprint cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for imprint

Every month we try and update this database with for imprint cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for imprint cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.