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 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: NRG-LU006NCI-2019-07141U10CA180868
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 12

Brief Summary

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.

Conditions

Pleural Biphasic Mesothelioma; Pleural Epithelioid Mesothelioma; Stage I Pleural Malignant Mesothelioma AJCC v8; Stage IA Pleural Malignant Mesothelioma AJCC v8; Stage IB Pleural Malignant Mesothelioma AJCC v8; Stage II Pleural Malignant Mesothelioma AJCC v8; Stage IIIA Pleural Malignant Mesothelioma AJCC v8

Keywords

Mesothelioma; IMPRINT

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Overall survival was to be estimated by the Kaplan-Meier method and arms were to be compared using a log-rank test. Analysis was to occur when at least 105 deaths had been reported. Given the small number of participants due to early study closure, only the number of patients last reported to be alive at time of study termination is reported.

  Randomization to the date of death or last follow-up. Maximum follow-up time from randomization was 25 months.

Secondary Outcomes (5)

• Local-failure-free Survival (LFFS)

  From randomization to local failure, death, or last follow-up, whichever occurs first. Maximum follow-up was 25 months.

• Distant-metastases-free Survival (DMFS)

  From randomization to distant failure, death, or last follow-up, whichever occurs first. Maximum follow-up was 25 months.

• Progression-free Survival (PFS)

  From randomization to first progression, death, or last follow-up, whichever occurs first. Maximum follow-up was 25 months.

• Number of Patients With Grade 3 or Higher Treatment-related Adverse Event After Randomization

  From randomization to death or last follow-up. Maximum follow-up time was 25 months.

• Change From Randomization to 9 Months in Global Heath Status (GHS) Score of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)

  Randomization and 9 months

Other Outcomes (3)

• Proportion of Patients With Under-staging, Concordant and Upstaging Between Centrally-reviewed Clinical Staging and Pathologic Staging

  Up to 5 years

• Association Between Radiation Dose to Gross Residual Disease and Local Control

  Up to 5 years

• Rate of R0/R1 and R2 Resections, by Type of Procedures (Extended Pleurectomy/Decortication (P/D), P/D and Partial Pleurectomy)

  Up to 5 years

Study Arms (2)

Arm I (Step 1: chemotherapy, P/D: Step 2: no treatment)

ACTIVE COMPARATOR

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.

Drug: Carboplatin; Drug: Cisplatin; Procedure: Decortication; Drug: Pemetrexed; Drug: Pemetrexed Disodium; Procedure: Pleurectomy

Arm II (Step 1: chemotherapy, P/D, Step 2: IMRT/PBS)

EXPERIMENTAL

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.

Drug: Carboplatin; Drug: Cisplatin; Procedure: Decortication; Radiation: Intensity-Modulated Radiation Therapy; Drug: Pemetrexed; Drug: Pemetrexed Disodium; Radiation: Pencil beam scanning proton therapy; Procedure: Pleurectomy

Interventions

Carboplatin DRUG

Intravenously

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm I (Step 1: chemotherapy, P/D: Step 2: no treatment); Arm II (Step 1: chemotherapy, P/D, Step 2: IMRT/PBS)

Cisplatin DRUG

Intravenously

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone''s Chloride, Peyrone''s Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm I (Step 1: chemotherapy, P/D: Step 2: no treatment); Arm II (Step 1: chemotherapy, P/D, Step 2: IMRT/PBS)

Decortication PROCEDURE

Undergo decortication

Arm I (Step 1: chemotherapy, P/D: Step 2: no treatment); Arm II (Step 1: chemotherapy, P/D, Step 2: IMRT/PBS)

Intensity-Modulated Radiation Therapy RADIATION

Daily fractions

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Arm II (Step 1: chemotherapy, P/D, Step 2: IMRT/PBS)

Pemetrexed DRUG

Intravenously

Also known as: MTA, Multitargeted Antifolate

Arm I (Step 1: chemotherapy, P/D: Step 2: no treatment); Arm II (Step 1: chemotherapy, P/D, Step 2: IMRT/PBS)

Pemetrexed Disodium DRUG

Intravenously

Also known as: Alimta, Almita, LY231514, N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt

Arm I (Step 1: chemotherapy, P/D: Step 2: no treatment); Arm II (Step 1: chemotherapy, P/D, Step 2: IMRT/PBS)

Pencil beam scanning proton therapy RADIATION

Daily fractions

Also known as: PBS proton therapy, intensity modulated proton therapy

Arm II (Step 1: chemotherapy, P/D, Step 2: IMRT/PBS)

Pleurectomy PROCEDURE

Undergo pleurectomy

Also known as: Excision of Pleura

Arm I (Step 1: chemotherapy, P/D: Step 2: no treatment); Arm II (Step 1: chemotherapy, P/D, Step 2: IMRT/PBS)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PRIOR TO STEP 1 REGISTRATION - ALL PATIENTS
• 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

You may not qualify if:

• PRIOR TO STEP 1 REGISTRATION - ALL PATIENTS
• 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

Sponsors & Collaborators

• NRG Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (12)

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MD Anderson in The Woodlands

Conroe, Texas, 77384, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MD Anderson West Houston

Houston, Texas, 77079, United States

Location

MD Anderson League City

League City, Texas, 77573, United States

Location

MD Anderson in Sugar Land

Sugar Land, Texas, 77478, United States

Location

Swedish Medical Center-First Hill

Seattle, Washington, 98122, United States

Location

MeSH Terms

Conditions

Mesothelioma, Malignant; Mesothelioma

Interventions

Carboplatin; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Cerebral Decortication; Radiotherapy, Intensity-Modulated; Pemetrexed

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Neurosurgical Procedures; Surgical Procedures, Operative; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Limitations and Caveats

This study stopped accrual early due to unmet targeted accrual goals with 16 subjects registered out of 140 planned (11 randomized out of 132 planned). Patients that were not randomized in Step 2 were not followed further. All data is reported as intent-to-treat except for the adverse event outcome measure, which is reported as as-treated.

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

215-574-3208

Study Officials

• Andreas Rimner, MD

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2019
• First Posted: November 8, 2019
• Study Start: January 29, 2020
• Primary Completion: November 20, 2023
• Study Completion: November 20, 2023
• Last Updated: April 24, 2026
• Results First Posted: February 19, 2025

Record last verified: 2026-04

Locations

US (12)