Immunotherapy + Chemotherapy + Surgery +/- Radiation for Mesothelioma

Not currently recruiting at 214 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune diseases, Severe infections, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments for pleural malignant mesothelioma, a cancer affecting the lung lining. It aims to determine how well the immune system can combat the cancer using atezolizumab (an immunotherapy), alongside chemotherapy drugs pemetrexed disodium and cisplatin, surgery, and possibly radiation. The trial seeks patients with stage I-III mesothelioma who have not received prior treatment and plan to undergo specific surgeries to remove the cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this combination of therapies.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention that you must not have had prior immunotherapy or chemotherapy for mesothelioma and should not be on any anticancer therapy or investigational agents within 28 days before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that atezolizumab, a treatment that boosts the immune system, caused lung inflammation related to the immune system in about 3% of patients. Although this is a concern, it is not common. Another study examined cisplatin, a chemotherapy drug, and identified serious side effects, such as kidney problems and nerve damage. Monitoring these side effects closely is important. Pemetrexed disodium, another chemotherapy drug, has been used safely in other studies, but it can lead to low blood cell counts. Lastly, extrapleural pneumonectomy, a surgery to remove a lung, has a low short-term death rate, but complications occur in about 60% of cases. While each treatment carries risks, researchers carefully monitor and manage side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for mesothelioma because it combines immunotherapy, chemotherapy, surgery, and possibly radiation in a novel way. Unlike standard treatments that typically focus on chemotherapy alone, this approach includes atezolizumab, an immunotherapy drug that helps the immune system specifically target cancer cells. By using atezolizumab alongside chemotherapy agents like cisplatin and pemetrexed disodium, the treatment aims to boost the body's natural defenses against cancer. Moreover, the integration of surgery and radiation offers a comprehensive strategy that could potentially improve outcomes for patients by targeting the cancer from multiple angles.

What evidence suggests that this trial's treatments could be effective for mesothelioma?

Studies have shown that atezolizumab can help shrink tumors or slow cancer growth in mesothelioma. In trials combining atezolizumab with chemotherapy, 55% of patients responded positively. In this trial, participants will receive a combination of atezolizumab, pemetrexed disodium, and cisplatin as part of the neoadjuvant treatment. When cisplatin was used with pemetrexed disodium, patients lived longer compared to using cisplatin alone, with an average increase in survival of 2.8 months. Extrapleural pneumonectomy (EPP), a major surgery to remove the lining around the lung, has resulted in varied survival times, with some patients living up to 27.5 months. This trial will explore whether combining these treatments, along with surgery and potentially radiation therapy, enhances outcomes. ^{1 6 7 8 9}

Who Is on the Research Team?

Anne S Tsao

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with stage I-III pleural malignant mesothelioma that can be removed by surgery. They must not have had prior immunotherapy or chemotherapy, severe infections, active tuberculosis, certain autoimmune diseases, or a history of significant allergic reactions to specific antibodies. Candidates should not have received any cancer treatments within the last 28 days and must meet various health criteria including organ function tests.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

If you need a hearing aid or have trouble hearing, you need to have a hearing test done within 28 days before joining the study.

Patient must be offered the opportunity to participate in tissue and blood banking for future studies

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive atezolizumab, pemetrexed disodium, and cisplatin intravenously every 21 days for 4 cycles

12 weeks

Surgery

Participants undergo extrapleural pneumonectomy or pleurectomy/decortication, with radiation therapy for those who undergo extrapleural pneumonectomy

3-12 weeks

Maintenance

Participants receive atezolizumab intravenously every 21 days for up to 1 year

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Cisplatin
• Extrapleural Pneumonectomy
• Pemetrexed Disodium
• Pleurectomy
• Radiation Therapy

Trial Overview

The study is testing the effectiveness of combining atezolizumab (an immune system booster), pemetrexed disodium (a cell growth blocker), and cisplatin (chemotherapy) followed by surgery and possibly radiation therapy in treating patients with mesothelioma. The goal is to shrink tumors before removal and eliminate remaining cancer cells after surgery.

How Is the Trial Designed?

Group I: Treatment (chemotherapy, surgery, RT) Experimental Treatment 6 Interventions

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.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In the KEYNOTE-158 study involving 118 patients with previously treated malignant pleural mesothelioma (MPM), pembrolizumab demonstrated an 8% objective response rate, with a median duration of response of 14.3 months, indicating its potential efficacy as a treatment option regardless of PD-L1 status.

The treatment was associated with manageable safety, as 69% of patients experienced treatment-related adverse events, with serious events occurring in 12%, highlighting the need for careful monitoring but suggesting that pembrolizumab can be tolerated in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab in patients with advanced mesothelioma in the open-label, single-arm, phase 2 KEYNOTE-158 study. Yap, TA., Nakagawa, K., Fujimoto, N., et al.[2021]

In a study of 903 patients with malignant pleural mesothelioma (MPM), pemetrexed combined with cisplatin was found to be generally well tolerated, with a low treatment-associated death rate of 0.8% and an interstitial lung disease (ILD) incidence of 0.9%.

The overall response rate to treatment was 25%, and the six-month survival rate was estimated at 75.9%, indicating that pemetrexed is effective in managing MPM, consistent with previous clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study. Kuribayashi, K., Voss, S., Nishiuma, S., et al.[2015]

Pemetrexed, when combined with cisplatin, significantly improves median survival in patients with malignant pleural mesothelioma, with a median survival of 12.1 months compared to 9.3 months for cisplatin alone, based on a phase III trial involving 448 patients.

The drug works by inhibiting key enzymes involved in DNA synthesis, but it can cause side effects like myelosuppression, neutropenia, and fatigue, necessitating supportive care with folic acid, vitamin B12, and corticosteroids during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: pemetrexed (Alimta). Hazarika, M., White, RM., Johnson, JR., et al.[2022]

In a study involving 567 patients with malignant mesothelioma, pemetrexed alone or in combination with cisplatin or carboplatin showed overall response rates of 16%, 24%, and 18%, respectively, indicating that these treatments are effective options for managing this condition.

Pemetrexed alone was found to be less toxic to the blood compared to the combination therapies, suggesting it may be a safer option for patients, especially those who have already undergone treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany. Reck, M., Stahel, RA., von Pawel, J., et al.[2015]

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