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
NCT ID: NCT04158141
Last Updated: 2025-02-19
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE3
16 participants
INTERVENTIONAL
2020-01-29
2023-11-20
Brief Summary
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Detailed Description
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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.
After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm I (Step 1: chemotherapy, P/D: Step 2: no treatment)
STEP 1: Patients who received allowed neoadjuvant systemic therapy before study entry undergo pleurectomy/decortication (P/D) within 4 to 8 weeks of systemic therapy. Otherwise, patients undergo P/D within 4 weeks of study entry followed within 4 to 8 weeks by four 21-day cycles of pemetrexed and cisplatin or carboplatin on day 1.
STEP 2: Patients receive no treatment.
Carboplatin
Intravenously
Cisplatin
Intravenously
Decortication
Undergo decortication
Pemetrexed
Intravenously
Pemetrexed Disodium
Intravenously
Pleurectomy
Undergo pleurectomy
Arm II (Step 1: chemotherapy, P/D, Step 2: IMRT/PBS)
STEP 1: Same as Arm 1.
STEP 2: Within 4-8 weeks from the end of Step 1 treatment, patients undergo 25-28 fractions of intensity modulated radiation therapy (IMRT) or pencil beam scanning (PBS) proton therapy 5 days/week over 6 weeks.
Carboplatin
Intravenously
Cisplatin
Intravenously
Decortication
Undergo decortication
Intensity-Modulated Radiation Therapy
Daily fractions
Pemetrexed
Intravenously
Pemetrexed Disodium
Intravenously
Pencil beam scanning proton therapy
Daily fractions
Pleurectomy
Undergo pleurectomy
Interventions
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Carboplatin
Intravenously
Cisplatin
Intravenously
Decortication
Undergo decortication
Intensity-Modulated Radiation Therapy
Daily fractions
Pemetrexed
Intravenously
Pemetrexed Disodium
Intravenously
Pencil beam scanning proton therapy
Daily fractions
Pleurectomy
Undergo pleurectomy
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Pathologically (histologically or cytologically) confirmed diagnosis of epithelioid or biphasic malignant pleural mesothelioma (MPM)
* Imaging proof of clinical stage (American Joint Committee on Cancer \[AJCC\] 8th edition) I-IIIA MPM by PET/CT;
* Diagnostic volumetric CT scan of the chest is preferred; however, the CT portion of the PET/CT may be used if CT imaging is of diagnostic quality
* MPM is amenable to resection by P/D as determined by a thoracic surgeon
* History/physical examination within 42 days prior to Step 1 Registration
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 within 42 days prior to Step 1 Registration
* Required Initial Laboratory Values prior to study entry (must be at least 14 days after last infusion of pre-study entry neoadjuvant therapy, if given):
* Absolute neutrophil count ≥1500 cells/mm3;
* Platelets ≥100,000 cells/mm3;
* Hemoglobin ≥ 8.0 g/dL;
* Serum total bilirubin ≤ 1.5 X ULN (upper limit of normal);
* Aspartate transferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and alanine transaminase (ALT) (serum glutamic-oxaloacetic transaminase (SGPT)) ≤ 3.0 X ULN;
* Creatinine clearance ≥45 mL/min by the Cockcroft-Gault (C-G) equation
* Negative serum pregnancy test within 14 days of Step 1 Registration for women of childbearing potential
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Note: HIV testing is not required for eligibility for this protocol.
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
PRIOR TO STEP 1 REGISRATION - PATIENTS WHO RECEIVED SYSTEMIC THERAPY BEFORE STUDY ENTRY
* The following systemic therapy and immunotherapy combinations are permissible: 1) cisplatin/carboplatin + pemetrexed; 2) cisplatin/carboplatin + pemetrexed + anti-PD-1/L1 agents; and 3) ipilimumab/nivolumab.
* Patients must have received at least 2 cycles of neoadjuvant systemic therapy
PRIOR TO STEP 2 RANDOMIZATION - ALL PATIENTS
* No evidence of progression as defined by PET/CT within 30 days prior to Step 2 randomization.
* Patients must have received at least 2 cycles of systemic therapy and undergone a pleurectomy/decortication with the goal of macroscopic complete resection;
* ECOG Performance Status 0-1 within 30 days prior to Step 2 Randomization
* History/physical examination within 30 days prior to Step 2 Randomization
Exclusion Criteria
* Pregnancy or women who are breastfeeding and unwilling to discontinue.
* Participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) unwilling to use highly effective contraceptives during and for six months after end of treatment because the treatment in this study may be significantly teratogenic.
* Diagnosis of sarcomatoid mesothelioma
* Severe, active co-morbidity defined as follows:
* New York Heart Association (NYHA) class III or IV heart failure
* Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of \> 10 mg prednisone daily or equivalent at the time of registration. Inhaled corticosteroids are allowed;
* Unstable angina requiring hospitalization and/or transmural myocardial infarction within the last 3 months;
* Interstitial lung disease;
* Hemodialysis or peritoneal dialysis;
* Concurrent active malignancy (with the exception of current or prior non-melanomatous skin cancer or low-grade malignancies followed observantly for which treatment has not or does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen)
* If evidence of disease \< 3 years, institution must consult with the principal investigator, Andreas Rimner, Doctor of Medicine (MD)
* Hepatic impairment defined by ChildPugh class (ChildPugh class B \& C);
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy within 30 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 30 days prior to registration
* • Active lung infection requiring IV antibiotics
* Patients on immunosuppressive therapy, for example history of organ or bone marrow transplant or other hematologic disorders that are expected to compromise life expectancy or tolerance of treatment;
* Prior nephrectomy on the contralateral side of MPM
* Ipsilateral thoracic electronic implant, e.g. pacemaker, defibrillator, unless switched to the contralateral side prior to initiation of radiation therapy (RT)
* Prior thoracic radiation therapy (patients with prior thoracic RT cannot be planned to 50-60 Gy without exceeding normal tissue constraints)
* Use of bevacizumab or other antiangiogenic therapy to treat current mesothelioma (due to potential for increased complications from local therapy).
* For patients who received neoadjuvant systemic therapy prior to study entry, surgery planned to occur greater than 8 weeks following neoadjuvant systemic therapy
PRIOR TO STEP 2 RANDOMIZATION - ALL PATIENTS
* Supplemental oxygen use
* Third space fluid that cannot be controlled by drainage or insufficient lung expansion after P/D (this prevents targeting the pleura without exceeding normal tissue constraints)
* Prior intrapleural therapy (i.e. intrapleural chemotherapy, photodynamic therapy); pleurodesis is permitted
* Bulky residual disease in the major fissure preventing pleural IMRT
* Patients who have undergone extrapleural pneumonectomy
* Patients with active infection that requires systemic I.V. antibiotics, antiviral, or antifungal treatments
18 Years
80 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
NRG Oncology
OTHER
Responsible Party
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Principal Investigators
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Andreas Rimner, MD
Role: PRINCIPAL_INVESTIGATOR
NRG Oncology
Locations
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UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Moffitt Cancer Center-International Plaza
Tampa, Florida, United States
Moffitt Cancer Center - McKinley Campus
Tampa, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, United States
Memorial Sloan Kettering Commack
Commack, New York, United States
Memorial Sloan Kettering Westchester
Harrison, New York, United States
Mount Sinai Hospital
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
MD Anderson in The Woodlands
Conroe, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States
M D Anderson Cancer Center
Houston, Texas, United States
MD Anderson West Houston
Houston, Texas, United States
MD Anderson League City
League City, Texas, United States
MD Anderson in Sugar Land
Sugar Land, Texas, United States
Swedish Medical Center-First Hill
Seattle, Washington, United States
The Research Institute of the McGill University Health Centre (MUHC)
Montreal, Quebec, Canada
Countries
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
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NCI-2019-07141
Identifier Type: REGISTRY
Identifier Source: secondary_id
NRG-LU006
Identifier Type: OTHER
Identifier Source: secondary_id
NRG-LU006
Identifier Type: OTHER
Identifier Source: secondary_id
NRG-LU006
Identifier Type: -
Identifier Source: org_study_id
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