Chemoimmunotherapy for Mesothelioma

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Robert Ripley, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Baylor College of Medicine

Must not be taking: Immunosuppressants, PD1/PD-L1 inhibitors

Disqualifiers: Autoimmune conditions, Heart disease, HIV, others

Stay on Your Current Meds

No Placebo Group

Breakthrough Therapy

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

Objectives: The investigators will test whether combination of chemoimmunotherapy or dual agent immunotherapy alone improves efficacy for patients with MPM. Primary Objectives: The primary objective is to test whether the combination of platinum-based chemotherapy and pemetrexed with durvalumab / tremelimumab or durvalumab / tremelimumab alone improves recurrence-free survival for patients with resectable MPM compared to historical, published data for surgery with chemotherapy. Secondary Objective(s): The secondary objectives are to determine the safety of and whether the platinum-based chemotherapy and pemetrexed with durvalumab / tremelimumab or durvalumab / tremelimumab alone improves response rate, resectability, major pathological response, and complete pathological response. Exploratory Objective(s): The exploratory objectives are to determine the safety of and whether the platinum-based chemotherapy and pemetrexed with durvalumab / tremelimumab or durvalumab / tremelimumab alone improves response rate, resectability, major pathological response, and complete pathological response for patients with epithelioid and non-epithelioid histologies. The scientific exploratory objectives include: 1. Develop an NGS plasma assay of common mutations identified from our previous grant cycle to prospectively measure minimal residual disease (MRD) after resection as a potential, novel biomarker test in mesothelioma. 2. Determine the predictive role of BH3 profiling in patients undergoing neoadjuvant ICI followed by surgery: With patient samples collected from our neoadjuvant ICI trial, the investigators will test whether BH3 profiling from pre-treatment tumor biopsies and PBMC predicts clinical, radiological, and pathological responses to ICIs. The investigators will identify TAMs from the TiME in MPM tumor samples before and after treatment to compare differences in polarization induced by ICI in clinical and pathologically responding versus non-responding patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have used immunosuppressive medication within 28 days before the trial, except for certain low-dose corticosteroids. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination used in the Chemoimmunotherapy for Mesothelioma trial?

Research shows that the combination of carboplatin and pemetrexed is effective and well-tolerated in treating malignant pleural mesothelioma, with some patients achieving a complete response. This combination is considered a feasible alternative to the standard cisplatin plus pemetrexed regimen, which is known to improve survival in mesothelioma patients. ^{1 2 3 4 5}

Is chemoimmunotherapy for mesothelioma safe?

Studies show that pemetrexed combined with cisplatin or carboplatin is generally safe for treating malignant pleural mesothelioma, though it can have side effects. Replacing cisplatin with carboplatin may reduce some side effects, making the treatment more tolerable. ^{1 2 4 5 6}

How is the chemoimmunotherapy drug for mesothelioma different from other drugs?

This treatment uses carboplatin instead of cisplatin, which may reduce side effects while maintaining effectiveness. It combines carboplatin or cisplatin with pemetrexed, a drug known to be effective in treating mesothelioma, and is part of a multimodal approach that includes surgery and radiotherapy for selected patients. ^{1 2 3 4 5}

Research Team

Robert Ripley, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for adults over 18 with mesothelioma that can potentially be removed by surgery. They should have no severe disease outside the chest area, normal organ and bone marrow function, and an ECOG performance status of 0 or 1 (fully active or restricted in physically strenuous activity but ambulatory). Pregnant women and those on immunosuppressants or with certain medical conditions are excluded.

Inclusion Criteria

I am not pregnant or cannot become pregnant.

I weigh more than 30 kilograms.

My cancer is in one side of my chest and surgery might be possible.

Exclusion Criteria

I have a history of HIV, hepatitis B or C, or another serious infection needing ongoing treatment.

I have an autoimmune disease but only take a low dose of prednisone or less.

I have had severe side effects from previous immunotherapy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive either dual immunotherapy with durvalumab and tremelimumab or chemotherapy plus dual immunotherapy for 3 cycles

9 weeks

3 visits (in-person)

Surgery

Participants undergo surgical resection if deemed resectable after induction treatment

1 week

Adjuvant Treatment

Participants continue adjuvant durvalumab for up to 12 months following surgery

12 months

Follow-up

Participants are monitored for recurrence-free survival and other outcomes

12 months

Treatment Details

Interventions

• Durvalumab (Checkpoint Inhibitor)
• Platinum cisplatin or carboplatin and pemetrexed chemotherapy (Chemotherapy)
• Tremelimumab (Checkpoint Inhibitor)

Trial Overview The study tests if adding durvalumab/tremelimumab to standard chemotherapy (cisplatin/carboplatin and pemetrexed) improves outcomes for mesothelioma patients who can undergo surgery. It compares this combination against using just durvalumab/tremelimumab without chemo, looking at survival rates without cancer recurrence.

Participant Groups

Group I: Platinum cisplatin or carboplatin and pemetrexed chemotherapy plus durvalumab/tremelimumab Experimental Treatment 1 Intervention

3 cycles of durvalumab (1500 mg intravenously) + tremelimumab (75 mg intravenously) with cisplatin 75mg/ m2 (or carboplatin AUC 5-6) + pemetrexed 500 mg/m2 (Cohort B).

Group II: Induction dual immunotherapy with durvalumab / tremelimumab Experimental Treatment 1 Intervention

3 cycles of durvalumab (1500 mg intravenously) + tremelimumab (75 mg intravenously) starting Cycle1 Day (Cohort A).

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Paul Klotman

Baylor College of Medicine

Chief Executive Officer since 2010

MD, PhD

James Versalovic

Baylor College of Medicine

Chief Medical Officer since 2020

MD from Baylor College of Medicine

Duke Cancer Institute

Collaborator

Trials

17

Recruited

3,000+

Findings from Research

In a study of 146 patients with malignant pleural mesothelioma, the combination of cis/carboplatin plus gemcitabine showed similar median survival rates (11.0 months) compared to cis/carboplatin plus pemetrexed (12.0 months), indicating that both treatment regimens are comparably effective.

Both treatment combinations were well tolerated with similar side effects, suggesting that cis/carboplatin plus gemcitabine is a safe alternative for patients, warranting further investigation in larger randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma. Ak, G., Metintas, S., Akarsu, M., et al.[2022]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

Carboplatin and pemetrexed in the management of malignant pleural mesothelioma: a realistic treatment option? [2015]

3. China pubmed.ncbi.nlm.nih.gov

A pathological complete response after preoperative chemotherapy with carboplatin and pemetrexed in malignant pleural mesothelioma: A case report. [2021]

4. Greece pubmed.ncbi.nlm.nih.gov

Pemetrexed plus carboplatin or cisplatin as neoadjuvant treatment of operable malignant pleural mesothelioma (MPM). [2015]

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

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. [2015]

6. 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]