Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Mesothelioma

Mesothelioma, Malignant

Lung Neoplasms

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Malignant Mesothelioma

Antineoplastic Agents

All Drugs and Chemicals

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Atezolizumab

Pemetrexed

Cisplatin

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Antibodies, Monoclonal

Immunoglobulins

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

Glutamic Acid

Folinic Acid

Folate

Vitamin B9

NEOADJUVANT: Patients receive atezolizumab IV over 30-60 minutes, pemetrexed disodium IV over 10 minutes, and cisplatin IV over 2 hours on day 1. Cycles repeats every 21 days for 4 cycles in the absence of disease progression or unexpected toxicity.

SURGERY: Within 21-90 days after completion of neoadjuvant therapy, patients undergo EPP or PD. Patients who undergo EPP will then undergo RT.

MAINTENANCE: Within 90 days after completion of either PD or radiation (post-EPP), patients receive atezolizumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 1 year in the absence of disease progression or unexpected toxicity.

Extrapleural Pneumonectomy

Pemetrexed Disodium

Pleurectomy

Radiation Therapy

Anne S Tsao

This phase I pilot trial studies how well atezolizumab, pemetrexed disodium, cisplatin, and surgery with or without radiation therapy works in treating patients with stage I-III pleural malignant mesothelioma. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, 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 atezolizumab, pemetrexed disodium, and cisplatin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving atezolizumab after surgery may kill any remaining tumor cells.

PRIMARY OBJECTIVE:

I. To evaluate if the regimen of neoadjuvant cisplatin-pemetrexed disodium (pemetrexed)-atezolizumab, surgery +/- radiation, then maintenance atezolizumab is feasible and safe for patients with resectable malignant pleural mesothelioma.

SECONDARY OBJECTIVES:

I. To evaluate progression free survival (both by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 and also using a modified RECIST for pleural tumors) in patients with resectable malignant pleural mesothelioma treated with a regimen of neoadjuvant cisplatin-pemetrexed-atezolizumab, surgery +/- radiation, followed by one year of maintenance atezolizumab.

II. To evaluate overall survival in patients with resectable malignant pleural mesothelioma treated with a regimen of neoadjuvant cisplatin-pemetrexed-atezolizumab, surgery +/- radiation, followed by one year of maintenance atezolizumab.

III. To evaluate response rate (confirmed and unconfirmed, complete and partial, both by RECIST 1.1 and also using a modified RECIST for pleural tumors) in the subset of this patient population with measurable disease.

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To evaluate the association between immunohistochemical (IHC) expression of PD-L1 in tumors and clinical outcomes in mesothelioma patients treated with trimodality/bimodality therapy including atezolizumab (anti-PD-L1).

II. To evaluate the association between expression of immune-related genes identified by Immune Nanostring (depending on ribonucleic acid \[RNA\] availability) and clinical outcomes in mesothelioma patients treated with trimodality/bimodality therapy including atezolizumab.

III. To evaluate the association between multiplex immunofluorescence (IF) of up to 10 immune markers in two panels and clinical outcomes in mesothelioma patients treated with trimodality/bimodality therapy including atezolizumab.

OUTLINE:

NEOADJUVANT: Patients receive atezolizumab intravenously (IV) over 30-60 minutes, pemetrexed disodium IV over 10 minutes, and cisplatin IV over 2 hours on day 1. Cycles repeats every 21 days for 4 cycles in the absence of disease progression or unexpected toxicity.

SURGERY: Within 21-90 days after completion of neoadjuvant therapy, patients undergo extrapleural pneumonectomy (EPP) or pleurectomy/decortication (PD). Patients who undergo EPP will then undergo radiation therapy (RT).

MAINTENANCE: Within 90 days after completion of either PD or radiation (post-EPP), patients receive atezolizumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 1 year in the absence of disease progression or unexpected toxicity.

After completion of study treatment, patients are followed up for up to 3 years.

Atezolizumab, Pemetrexed Disodium, Cisplatin, and Surgery With or Without Radiation Therapy in Treating Patients With Stage I-III Pleural Malignant Mesothelioma

A Feasibility Trial of Neoadjuvant Cisplatin-Pemetrexed With Atezolizumab in Combination and in Maintenance for Resectable Malignant Pleural Mesothelioma

The number of participants who received at least two cycles of the triplet neoadjuvant therapy getting at least one dose of maintenance therapy.

The number of participants that experienced a Grade 4-5 immune-related adverse event. The regimen was considered safe if no participants experienced a Grade 4-5 immune-related AE.

From date of registration to Step 1 to date of first documentation of progression by RECIST 1.1 and modified RECIST 1.1, symptomatic deterioration, or death due to any cause. Participants last known to be alive and progression free are censored at date of last disease assessment.

From date of initial registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact.

Percentage of participants with confirmed and unconfirmed, complete and partial, defined by RECIST 1.1 and mRECIST for Pleural Tumors

National Cancer Institute (NCI)

CTCAE version 5.0 was used for reporting SAEs and routine toxicity reporting. There were 28 participants on registration Step 1 (Neoadjuvant) that were assessed for AEs, 19 participants on registration Step 2 (Surgery) that were assessed for AEs, and 15 participants on registration Step 3 (Maintenance) that were assessed for AEs.

Participants receive atezolizumab IV over 30-60 minutes, pemetrexed disodium IV over 10 minutes, and cisplatin IV over 2 hours on day 1. Cycles repeats every 21 days for 4 cycles in the absence of disease progression or unexpected toxicity.

Chemotherapy + Atezolizumab

Within 21-90 days after completion of neoadjuvant therapy, participants undergo EPP or PD. Participants who undergo EPP will then undergo RT.

Surgery

Within 90 days after completion of either PD or radiation (post-EPP), participants receive atezolizumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 1 year in the absence of disease progression or unexpected toxicity.

Maintenance

NEOADJUVANT: Patients receive atezolizumab IV over 30-60 minutes, pemetrexed disodium IV over 10 minutes, and cisplatin IV over 2 hours on day 1. Cycles repeats every 21 days for 4 cycles in the absence of disease progression or unexpected toxicity.

SURGERY: Within 21-90 days after completion of neoadjuvant therapy, patients undergo extrapleural pneumonectomy (EPP) or pleurectomy/decortication (PD). Patients who undergo EPP will then undergo radiation therapy.

MAINTENANCE: Within 90 days after completion of either PD or radiation (post-EPP), patients receive atezolizumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 1 year in the absence of disease progression or unexpected toxicity.

Treatment (Chemotherapy, Surgery +/- RT, Maintenance)

Age, Continuous

Sex: Female, Male

Hispanic

Race/Ethnicity, Customized

Race

Performance Status uses the Zubrod Scale as follows:

0 - Fully active, able to carry on all pre-disease performance w/o restriction

1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work

Performance Status

Weight Loss Past 6 Months

Baseline Disease Status mRECIST

Baseline Disease Status RECIST

Lung Committee Statistician

Participants that received at least 2 cycles of neoadjuvant Cisplatin-Pemetrexed-Atezolizumab.

Feasibility of Neoadjuvant Cisplatin-Pemetrexed-Atezolizumab, Surgery +/- Radiation, and Maintenance Therapy.

Participants who were assessed for adverse events.

Safety of Neoadjuvant Cisplatin-Pemetrexed-Atezolizumab, Surgery +/- Radiation, and Maintenance Therapy.

RECIST 1.1

mRECIST 1.1

Progression Free Survival (PFS)

Overall Survival (OS)

Eligible and evaluable participants with measurable disease. 14 participants had measurable disease according to the RECIST which measures lesions from an x-ray, CT, or MRI. 22 participants had measurable disease according to the mRECIST which measures lesions as the sum of 6 CT cuts.

Response Rate (RR)

Neoadjuvant

Spots Global Cancer Trial Database for extrapleural pneumonectomy