Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical 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. 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.
Phase
Phase 3
Funding Agency/Sponsor
National Cooperative Group
Disease
Thoracic Oncology
Enrollment Eligibility
Inclusion Criteria:
PRIOR TO STEP 1 REGISTRATION INCLUSION CRITERIA
- Pathologically (histologically or cytologically) confirmed diagnosis of epithelioid or
biphasic malignant pleural mesothelioma (MPM) within 90 days prior to Step 1
Registration
- Imaging proof of clinical stage (American Joint Committee on Cancer [AJCC] 8th
edition) I-IIIA MPM by PET/CT within 42 days prior to Step 1 Registration
- MPM is amenable to resection by P/D as determined by a thoracic surgeon within 42 days
prior to Step 1 Registration
- History/physical examination within 42 days prior to Step 1 Registration
- Karnofsky performance status >= 80 within 42 days prior to Step 1 Registration
- Pulmonary function tests within 42 days prior to Step 1 Registration:
- >= 40% predicted post-forced expiratory volume in 1 second (FEV1);
- >= 40% predicted post-operative diffusion capacity of the lung for carbon
monoxide (DLCO) (corrected for hemoglobin [Hgb])
- Leukocytes >= 3000 cells/mm^3 (within 30 days prior to Step 1 Registration)
- Absolute neutrophil count >= 1500 cells/mm^3 (within 30 days prior to Step 1
Registration)
- Platelets >= 100,000 cells/mm^3 (within 30 days prior to Step 1 Registration)
- Serum total bilirubin =< 1.5 X upper limit of normal (ULN) (within 30 days prior to
Step 1 Registration)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 X
ULN (within 30 days prior to Step 1 Registration)
- Glomerular filtration rate (GFR): >= 50 mL/min/1.73 m^2 (must be calculated using
estimated creatinine clearance [CrCl] by the Cockcroft-Gault [C-G] equation [Nephron
1976;16:31-41]) (within 30 days prior to Step 1 Registration)
- Negative serum pregnancy test within 14 days of Step 1 Registration for pre-menopausal
women of childbearing potential
- The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry
- EORTC QLQ-C30 and QLQ-LC13 within 42 days prior to Step 1 Registration PRIOR TO STEP 2
RANDOMIZATION INCLUSION CRITERIA
- Patients must have received at least 2 cycles of pemetrexed/platinum chemotherapy and
undergone a pleurectomy/decortication with the goal of macroscopic complete resection
following step 1 Registration
- Karnofsky performance status >= 70 within 30 days prior to Step 2 Randomization
- History/physical examination within 30 days prior to Step 2 Randomization
- EORTC QLQ-C30 and QLQ-LC13 within 30 days prior to Step 2 Randomization
Exclusion Criteria:
PRIOR TO STEP 1 REGISTRATION EXCLUSION CRITERIA
- Pregnant or lactating women, or sexually active men or women not using effective
contraception (risk for fetal defects from teratogenic chemotherapy and radiation
therapy) within 14 days prior to Step 1 Registration
- 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 tuberculosis
- Patients on immunosuppressive therapy, for example history of organ or bone
marrow transplant or chronic lymphocytic leukemia (CLL);
- CD4 count < 200 cells/microliter. Note that patients who are human
immunodeficiency virus (HIV) positive are eligible, provided they are under
treatment with highly active antiretroviral therapy (HAART) and have a CD4 count
>= 200 cells/microliter within 30 days prior to registration. Note also that HIV
testing is not required for eligibility for this protocol
- 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)
PRIOR TO STEP 2 RANDOMIZATION EXCLUSION CRITERIA
- Progressive disease
- 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