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Pleural Biphasic MesotheliomaPhase 3NCT04158141

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

A Phase 3 study testing Carboplatin, Cisplatin and Decortication in people with Pleural Biphasic Mesothelioma and Pleural Epithelioid Mesothelioma, run by NRG Oncology at 12 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Carboplatin, Cisplatin and Decortication
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
12 sitesUnited States
Study dates
29 Jan 2020to 20 Nov 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
Show all 29Show fewer
  • 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

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • MD Anderson in The Woodlands

    Conroe, Texas, 77384

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • MD Anderson West Houston

    Houston, Texas, 77079

  • UT MD Anderson - League City

    League City, Texas, 77573

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Swedish Medical Center-First Hill

    Seattle, Washington, 98122

  • MD Anderson in Sugar Land

    Sugar Land, Texas, 77478

Other trials in United States

About this study

Official title: 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)

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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).

  1. 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.

Being tested
Carboplatin, Cisplatin, Decortication, Intensity-Modulated Radiation Therapy, Pemetrexed
Keywords
Mesothelioma, IMPRINT
Medical subject headings
Mesothelioma, Malignant, Mesothelioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Intravenously

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Intravenously

  • DecorticationProcedure or surgery

    Undergo decortication

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

    Daily fractions

  • PemetrexedDrug

    Also called MTA, Multitargeted Antifolate

    Intravenously

  • Pemetrexed DisodiumDrug

    Also called 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

    Intravenously

  • Pencil beam scanning proton therapyRadiation

    Also called PBS proton therapy, intensity modulated proton therapy

    Daily fractions

  • PleurectomyProcedure or surgery

    Also called Excision of Pleura

    Undergo pleurectomy

Study groups in NCT04158141
Study groupRoleWhat they receive
Arm I (Step 1: chemotherapy, P/D: Step 2: no treatment)Active comparatorSTEP 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.
Receives: Drug: Carboplatin; Drug: Cisplatin; Procedure: Decortication; Drug: Pemetrexed; Drug: Pemetrexed Disodium; Procedure: Pleurectomy
Arm II (Step 1: chemotherapy, P/D, Step 2: IMRT/PBS)ExperimentalSTEP 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.
Receives: Drug: Carboplatin; Drug: Cisplatin; Procedure: Decortication; Radiation: Intensity-Modulated Radiation Therapy; Drug: Pemetrexed; Drug: Pemetrexed Disodium; Radiation: Pencil beam scanning proton therapy; Procedure: Pleurectomy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (5)

  1. Local-failure-free Survival (LFFS)

    Local failure is defined as local enlargement (LE) or local failure (LF) tumor response, marginal failure (MF), or death. LFFS was to be estimated by the Kaplan-Meier method and arms compared by 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 without failure at time of study termination is reported, and no statistical testing was done.

    LE: ≥ 20% increase in the largest diameter (LD) of target lesion from the smallest LD recorded since the treatment start; based on computed tomography (CT) scan.

    LF: Progression of pleural tumor thickness or appearance of a site of pleural thickness > 5 mm in the site of treated tumor.

    MF: The appearance of a new measurable site of pleural tumor > 5mm within the treated site or enlarging tumor dimensions corresponding to a 20% increase in LD compared to initial appearance on imaging evaluation.

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

  2. Distant-metastases-free Survival (DMFS)

    Distant failure (DF) is defined as the appearance of cancer deposits characteristic of metastatic dissemination from mesothelioma. DMFS 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 without failure at time of study termination is reported, and no statistical testing was done.

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

  3. Progression-free Survival (PFS)

    Progression is defined as LE, LF, MF, DF, or death. PFS was to be estimated by the Kaplan-Meier method and arms compared by log-rank test. Analysis was to occur when ≥ 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 without progression at study termination is reported, and no statistical testing was done.

    LE: ≥ 20% increase in the largest diameter (LD) of target lesion from the smallest LD recorded since the treatment start; based on CT scan.

    LF: Progression of pleural tumor thickness or appearance of a site of pleural thickness > 5 mm in the site of treated tumor.

    MF: The appearance of a new measurable site of pleural tumor > 5mm within the treated site or enlarging tumor dimensions corresponding to a 20% increase in LD compared to initial appearance on imaging evaluation.

    DF: The appearance of cancer deposits characteristic of metastatic dissemination

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

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

    Common Terminology Criteria for Adverse Events (version 5.0) grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Adverse events reported as possibly, probably, or definitely related to treatment are considered to be treatment-related adverse events.

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

  5. 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)

    Global Health Status is calculated from two questions on the EORTC QLQ-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best).

    Measured: Randomization and 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Nov 2019
  2. Study start29 Jan 2020
  3. Primary completion20 Nov 2023
  4. Study completion20 Nov 2023

Why it stopped: Permanent Administrative Closure

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04158141
Sponsor's protocol ID
NRG-LU006
Other IDs
NCI-2019-07141, NRG-LU006, NRG-LU006, U10CA180868
Status last verified
Jun 2026
First submitted
5 Nov 2019
Last updated
13 Jul 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Carboplatin, Cisplatin and Decortication in people with Pleural Biphasic Mesothelioma and Pleural Epithelioid Mesothelioma, run by NRG Oncology at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: Randomization to the date of death or last follow-up. Maximum follow-up time from randomization was 25 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04158141.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2026.

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