Immunotherapy + Chemotherapy + Surgery +/- Radiation for Mesothelioma

Recruiting at 210 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

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

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 the combination of pemetrexed and cisplatin safe for treating mesothelioma?

The combination of pemetrexed and cisplatin has been studied for safety in patients with malignant pleural mesothelioma. Common side effects include low white blood cell counts (neutropenia and leukopenia), tiredness (fatigue), nausea, difficulty breathing (dyspnea), and vomiting. Patients are advised to take folic acid and vitamin B12 to reduce severe side effects. ^{1 2 3 4 5}

How is the treatment with Atezolizumab, Cisplatin, Extrapleural Pneumonectomy, and Pemetrexed Disodium unique for mesothelioma?

This treatment is unique because it combines immunotherapy (Atezolizumab) with chemotherapy (Cisplatin and Pemetrexed Disodium), surgery (Extrapleural Pneumonectomy), and possibly radiation, offering a comprehensive approach that targets the cancer in multiple ways. The addition of Atezolizumab, an immune checkpoint inhibitor, is novel as it may enhance the body's immune response against the cancer, which is not a standard part of traditional mesothelioma treatments. ^{4 6 7 8 9}

What data supports the effectiveness of the treatment for mesothelioma?

Research shows that combining pemetrexed and cisplatin improves survival in mesothelioma patients compared to cisplatin alone, and this combination is considered a standard treatment. Additionally, studies indicate that using chemotherapy before surgery and radiation is safe and effective, potentially leading to better outcomes. ^{4 6 10 11 12}

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 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]

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 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]

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]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Multimodality therapy in mesothelioma: role of chemotherapy. [2007]

3. England pubmed.ncbi.nlm.nih.gov

Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany. [2015]

4. Ireland pubmed.ncbi.nlm.nih.gov

Raltitrexed plus cisplatin is cost-effective compared with pemetrexed plus cisplatin in patients with malignant pleural mesothelioma. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Current treatments for inoperable mesothelioma: indirect comparisons based on individual patient data reconstructed retrospectively from 4 trials. [2023]

6. England pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: pemetrexed (Alimta). [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Pemetrexed alone or in combination with cisplatin in previously treated malignant pleural mesothelioma: outcomes from a phase IIIB expanded access program. [2015]

9. England 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. [2021]

10. England pubmed.ncbi.nlm.nih.gov

A feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation for malignant pleural mesothelioma. [2015]

11. United States pubmed.ncbi.nlm.nih.gov

A Phase II Trial of Nivolumab With Chemotherapy Followed by Maintenance Nivolumab in Patients With Pleural Mesothelioma After Surgery: The NICITA Study Protocol. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Trimodality therapy with induction chemotherapy followed by extrapleural pneumonectomy and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma. [2022]