Chemotherapy + Immunotherapy for Mesothelioma

Recruiting at 38 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, NSAIDs

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: 12 weeks

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding immunotherapy, which helps the immune system fight cancer, to standard chemotherapy can more effectively treat peritoneal mesothelioma, a rare abdominal cancer. One group receives standard chemotherapy, while the other receives standard chemotherapy plus an immunotherapy drug called atezolizumab (Tecentriq). This trial may suit individuals with peritoneal mesothelioma who have not received prior treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had prior systemic therapy for peritoneal mesothelioma, and you should not use NSAIDs like ibuprofen around the time of pemetrexed administration if your creatinine clearance is between 45 and 79 mL/min. Also, you should not be on immunosuppressive medication within 2 weeks before starting the trial, except for certain low-dose or specific medications. It's best to discuss your current medications with the trial team.

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

Research has shown that using carboplatin, pemetrexed, and bevacizumab together is generally safe. In one study, patients tolerated this combination well, experiencing mainly common side effects like tiredness and nausea.

Adding atezolizumab to this mix has also undergone study. Trial data indicate that patients typically manage this addition without new safety issues. The most common side effects include tiredness and reduced appetite, typical for treatments involving both chemotherapy and immunotherapy.

Overall, current research supports that both treatment options are well-tolerated. Prospective trial participants can find reassurance in these findings regarding the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for mesothelioma because they combine chemotherapy with immunotherapy, aiming to enhance the body's natural ability to fight cancer. Unlike standard treatments, which typically focus on chemotherapy alone, these investigational treatments add bevacizumab and atezolizumab, which target blood vessels that feed tumors and boost the immune response, respectively. This dual approach has the potential to improve outcomes by not just attacking the cancer directly but also by strengthening the body's immune defense against it.

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

In this trial, one group of participants will receive a combination of three drugs—carboplatin, pemetrexed, and bevacizumab. Research shows that this combination may help treat mesothelioma, a type of cancer. In previous studies, patients lived for about 15.3 months on average with this treatment. Another group will receive these three drugs along with atezolizumab, which helps the immune system fight cancer. Although studies have not yet shown that adding atezolizumab significantly increases patient survival, the treatment aims to slow cancer growth and improve outcomes. ^{1 5 6 7 8}

Who Is on the Research Team?

Aaron S Mansfield, MD

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

Adults with untreated malignant peritoneal mesothelioma, without a history of central nervous system disease, significant bleeding disorders, or severe heart conditions. They must have functioning major organs and no autoimmune diseases (with some exceptions like controlled thyroid issues). Women must not be pregnant or nursing and agree to use birth control.

Inclusion Criteria

Your AST and ALT levels should not be more than three times the upper limit of normal.

Your disease must be able to be measured using specific guidelines.

I haven't had a biopsy or minor surgery, except for a device placement, in the last 7 days.

Exclusion Criteria

I agree to use effective birth control during the study due to the risk of birth defects.

Physicians should consider whether any of the following may render the patient inappropriate for this protocol: Psychiatric illness which would prevent the patient from giving informed consent

I do not have any uncontrolled conditions like infection, diabetes, or heart disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive chemotherapy with or without immunotherapy every 21 days for up to 4 cycles, followed by surgery and HIPEC if eligible

12 weeks

4 visits (in-person)

Maintenance Therapy

Patients not eligible for surgery may receive maintenance therapy every 21 days in the absence of disease progression or unacceptable toxicity

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab
• Carboplatin
• Pemetrexed

Trial Overview The trial is testing the effectiveness of adding immunotherapy (atezolizumab) to the usual treatment for peritoneal mesothelioma which includes surgery and chemotherapy drugs like carboplatin and pemetrexed. The goal is to see if atezolizumab helps the immune system fight cancer better than standard treatments alone.

How Is the Trial Designed?

Group I: Arm I (carboplatin, pemetrexed, bevacizumab, atezolizumab) Experimental Treatment 9 Interventions

Patients receive atezolizumab IV over 30-60 minutes, bevacizumab IV over 30-90 minutes, carboplatin IV over 30 minutes, and pemetrexed IV over 10 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 4-8 weeks, patients then undergo cytoreductive surgery and HIPEC. Patients not eligible for surgery may receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1 of each maintenance therapy cycle. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan, PET scan, and collection of blood and tissue samples throughout the study.

Group II: Arm II (carboplatin, pemetrexed, bevacizumab) Active Control 8 Interventions

Patients receive bevacizumab IV over 30-90 minutes, carboplatin IV over 30 minutes, and pemetrexed IV over 10 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 4-8 weeks, patients then undergo cytoreductive surgery and HIPEC. Patients not eligible for surgery may receive bevacizumab IV over 30-90 minutes with or without atezolizumab IV over 30-60 minutes on day 1 of each maintenance therapy cycle at the discretion of the investigator. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan, PET scan, and collection of blood and tissue samples throughout the study.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

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 812 patients with malignant pleural mesothelioma (MPM), single-agent pemetrexed showed promising efficacy, with a median time to progressive disease of 6.0 months for chemonaïve patients and an overall response rate of 10.5%.

The treatment was well-tolerated, exhibiting mild hematologic toxicity, primarily neutropenia, in less than 18% of patients, indicating a favorable safety profile for pemetrexed in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. Taylor, P., Castagneto, B., Dark, G., et al.[2015]

Two cases of anaphylactic reactions to cisplatin in patients treated for pleural mesothelioma highlight the potential for hypersensitivity to platinum-based chemotherapy, occurring after multiple treatment cycles.

Skin tests and flow cytometry were effective methods for confirming the diagnosis of hypersensitivity, indicating their utility in managing patients undergoing platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Investigation of allergic reactions to platinum salts]. Touraine, F., Sainte Laudy, J., Boumediene, A., et al.[2019]

A case report highlights a patient with malignant pleural mesothelioma achieving a complete pathological response after receiving four cycles of preoperative chemotherapy with carboplatin and pemetrexed, followed by surgery.

The carboplatin plus pemetrexed regimen was well tolerated, showing no severe hematological toxicity, suggesting it could be a safer alternative to the standard cisplatin plus pemetrexed treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pathological complete response after preoperative chemotherapy with carboplatin and pemetrexed in malignant pleural mesothelioma: A case report. Pasello, G., Altavilla, G., Bonanno, L., et al.[2021]

The EMPHACIS trial, a phase III study involving pemetrexed combined with cisplatin, demonstrated significant improvement in survival for patients with malignant pleural mesothelioma compared to standard treatments.

Supplementation with low-dose folic acid and vitamin B12 significantly reduced the toxicity associated with the pemetrexed/cisplatin regimen, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed (Alimta, MTA, multitargeted antifolate, LY231514) for malignant pleural mesothelioma. Manegold, C.[2019]

Pemetrexed, a treatment for malignant pleural mesothelioma and non-small cell lung cancer, has been associated with a new toxicity resembling scleroderma, as seen in two cases involving painful induration and edema of the lower extremities.

This adverse effect can be mistaken for erysipelas due to similar symptoms, but it lacks fever; recognizing this toxicity is crucial for timely diagnosis and management, and folate and vitamin B12 supplementation may help reduce its incidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pemetrexed-induced scleroderma-like changes in the lower legs]. Corbaux, C., Marie, J., Meraud, JP., et al.[2015]

Pemetrexed is an FDA-approved anti-folate agent used to treat malignant pleural mesothelioma and previously treated non-small cell lung cancer, showing efficacy in these patient populations.

In clinical trials, rash occurred in 17-22% of patients treated with pemetrexed, and this report highlights a specific case of rash due to urticarial vasculitis, contributing to the understanding of pemetrexed's side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed-associated urticarial vasculitis. Lopes, G., Vincek, V., Raez, LE.[2015]

In a phase II study involving 62 patients with unresectable malignant pleural mesothelioma (MPM), the combination of carboplatin and pemetrexed showed significant activity, with 29% of patients achieving a confirmed partial response and 54.9% maintaining stable disease.

The median overall survival for patients was 14 months, with a notable difference in survival based on histologic subtype, highlighting the efficacy of this chemotherapy regimen as a first-line treatment option for MPM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin plus pemetrexed as first-line treatment of patients with malignant pleural mesothelioma: a phase II study. Katirtzoglou, N., Gkiozos, I., Makrilia, N., et al.[2015]

Pemetrexed, especially when combined with cisplatin, has shown significantly higher efficacy in treating malignant pleural mesothelioma (MPM) compared to cisplatin alone, with a response rate of 41.3% and a median survival of 12.1 months versus 9.3 months for cisplatin.

In addition to improved survival rates, the pemetrexed/cisplatin combination also resulted in better quality of life and pulmonary function for patients, highlighting its potential as a more effective treatment option for MPM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in malignant pleural mesothelioma. Gatzemeier, U.[2015]

In a study of 51 patients with malignant pleural mesothelioma, both pemetrexed with carboplatin (AC) and pemetrexed with cisplatin (AP) were found to be effective neoadjuvant chemotherapy regimens, with similar rates of disease control and surgical resection (81% for AC and 79% for AP).

However, the AP regimen was associated with a higher incidence of severe side effects, such as grade 3 anemia and increased fatigue, which could negatively affect patients' overall health and their ability to undergo surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus carboplatin or cisplatin as neoadjuvant treatment of operable malignant pleural mesothelioma (MPM). Pasello, G., Marulli, G., Polo, V., et al.[2015]

In a large study involving 1704 chemonaïve patients with malignant pleural mesothelioma, pemetrexed combined with cisplatin showed a higher response rate (26.3%) compared to pemetrexed with carboplatin (21.7%).

Both treatment combinations resulted in similar 1-year survival rates (63.1% for cisplatin and 64.0% for carboplatin) and median time to disease progression, indicating that both regimens are effective options for patients not eligible for curative surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaïve patients with malignant pleural mesothelioma: results of the International Expanded Access Program. Santoro, A., O'Brien, ME., Stahel, RA., 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3738125/

Phase II study of pemetrexed and carboplatin plus ... Median PFS and overall survival were 6.9 and 15.3 months, respectively. Haematological and non-haematological toxicities were generally mild; ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00604461

Carboplatin, Bevacizumab and Pemetrexed in the First- ... The purpose of this research study was to evaluate how effective the combination of Carboplatin, Bevacizumab (Avastin™) and, Pemetrexed (Alimta™) is in the ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673615012386

Bevacizumab for newly diagnosed pleural mesothelioma in ... Findings from a phase 2 study also showed a median OS of 12·7 months and a median PFS of 6·5 months with pemetrexed plus carboplatin for advanced malignant ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00003-1/abstract

results of the ETOP 13-18 BEAT-meso trial At a median follow-up of 35 months (data cut-off 1 September 2023), the median OS was 20.5 months for ABC versus 18.1 months for BC [HR 0.84, 95 ...

5. ascopubs.org ascopubs.org/doi/10.1200/OP.21.00785

Systemic Therapy for Mesothelioma: Turning the Corner ... bevacizumab to pemetrexed and platinum improved progression-free survival and OS. CALGB 30901 suggested no benefit for pemetrexed maintenance.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39814199/

results of the ETOP 13-18 BEAT-meso trial A randomised phase III study of bevacizumab and carboplatin-pemetrexed chemotherapy with or without atezolizumab as first-line treatment for advanced pleural ...

7. karger.com karger.com/cro/article/18/1/278/919927/Successful-Response-to-First-Line-Carboplatin

Successful Response to First-Line Carboplatin ... Based on the Surveillance Epidemiology and Results (SEER) database, median overall survival (OS) for PeM is 8 months [1]. Systemic chemotherapy ...

8. eviq.org.au eviq.org.au/getmedia/8aa4d167-c71c-493d-8445-457a93424e7d/ID-4143-Mesothelioma-carboplatin-pemetrexed-and-bevacizumab-protocol-and-PI.pdf.aspx

Mesothelioma cARBOplatin pemetrexed and beVACizumab ** It is the consensus of the eviQ reference committee that it is safe to give the initial and subsequent doses of bevacizumab over. 30 minutes.