Chemoimmunotherapy for Mesothelioma

Recruiting at 1 trial location

Overseen By Monica Vilchis

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

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 You can continue your current medications while participating

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment combinations for mesothelioma, a cancer often linked to asbestos exposure. Researchers aim to determine if combining chemotherapy drugs with immune-boosting drugs (immunotherapies) can help prevent cancer recurrence after surgery. Participants will receive either a combination of chemotherapy (platinum cisplatin or carboplatin and pemetrexed) and two immunotherapy drugs (Durvalumab and Tremelimumab) or only the immunotherapy drugs. This trial may suit individuals with mesothelioma that can potentially be surgically removed and who haven't undergone certain previous treatments. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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.

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

Research has shown that combining platinum-based chemotherapy with the drugs durvalumab and tremelimumab has been safe in past studies. Most people tolerate the treatment well, though some serious side effects have occurred. In about 8% of patients in previous trials, fatal side effects, including rare cases of severe bleeding and heart problems, were reported.

When using durvalumab and tremelimumab alone, studies found that side effects are usually manageable. A small number of patients had to stop treatment due to these side effects. Overall, the combination has shown promising results, suggesting it could benefit patients with mesothelioma.

These treatments are still under study, and researchers continue to work on understanding their safety. Participation in these trials helps gather important information that could lead to better treatments in the future. ^{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 innovative immunotherapy agents. Unlike standard treatments that typically involve chemotherapy alone, this approach introduces durvalumab and tremelimumab, which are designed to boost the body's immune system to better recognize and attack cancer cells. These immunotherapy drugs target specific immune checkpoints, potentially leading to a more effective response against the tumor. This combination could enhance the effectiveness of traditional chemotherapy, offering new hope for patients with this challenging condition.

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

This trial will evaluate two different treatment approaches for mesothelioma. One arm involves induction dual immunotherapy with durvalumab and tremelimumab. The other arm combines these immune drugs with platinum-based chemotherapy, including cisplatin or carboplatin and pemetrexed. Research has shown that combining chemotherapy with durvalumab and tremelimumab may be promising for treating mesothelioma. In one study, 20% of patients who received these drugs were still alive after three years. Specifically, adding chemotherapy improved treatment effectiveness, with patients living between 10 to 18 months. This combination aims to attack cancer cells and strengthen the body's immune system. Early results suggest these treatments might be more effective against mesothelioma than traditional methods alone. ^{1 3 6 7 8}

Who Is on the Research Team?

Robert Ripley, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Platinum cisplatin or carboplatin and pemetrexed chemotherapy
• Tremelimumab

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.

How Is the Trial Designed?

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).

Platinum cisplatin or carboplatin and pemetrexed chemotherapy is already approved in United States, European Union for the following indications:

Approved in United States as Cisplatin for:

• Testicular cancer
• Ovarian cancer
• Lung cancer
• Bladder cancer
• Stomach cancer

Approved in United States as Carboplatin for:

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

Approved in United States as Pemetrexed for:

• Pleural mesothelioma
• Non-small cell lung cancer

Approved in European Union as Cisplatin for:

• Testicular cancer
• Ovarian cancer
• Lung cancer
• Bladder cancer
• Stomach cancer

Approved in European Union as Carboplatin for:

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

Approved in European Union as Pemetrexed for:

• Pleural mesothelioma
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Duke Cancer Institute

Collaborator

Trials

17

Recruited

3,000+

Published Research Related to This Trial

In a study of 49 patients with malignant pleural mesothelioma, the combination of carboplatin and pemetrexed achieved a disease control rate of 69% and a median overall survival of 14 months, indicating its effectiveness as a treatment option.

The treatment was generally well-tolerated, with only 14.3% of patients experiencing severe haematological toxicities and 24.5% experiencing severe non-haematological toxicities, and no toxic deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and pemetrexed in the management of malignant pleural mesothelioma: a realistic treatment option? Li, L., Razak, AR., Hughes, A.[2015]

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 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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9765708/

Tremelimumab plus durvalumab retreatment and 4-year ... At data cut-off, April 30, 2020, five (13%) of 40 patients enrolled in the NIBIT-MESO-1 study were alive, and 35 (88%) patients had died of progressive disease.

2. asbestos.com asbestos.com/news/2022/12/19/mesothelioma-surgery-immunotherapy-study/

Mesothelioma Surgery With Immunotherapy Proves ... Progression-free and median overall survival for those receiving only durvalumab was 8.4 months and 14 months, respectively. Those receiving no ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33844995/

Tremelimumab plus durvalumab retreatment and 4-year ... Survival was 20% (eight of 40 patients) at 36 months and 15% (six of 40 patients) and 48 months. 17 (43%) of 40 patients met the criteria for ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-04597

Durvalumab and Tremelimumab with or without ... This phase Ib/IIa trial tests the safety, side effects and effectiveness of durvalumab and tremelimumab with or without chemotherapy (cisplatin, carboplatin ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05932199

Study Details | NCT05932199 | Neoadjuvant Durvalumab ... Objectives: The investigators will test whether combination of chemoimmunotherapy or dual agent immunotherapy alone improves efficacy for patients with MPM.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.35.15_suppl.8558

Safety analysis from the phase II NIBIT-MESO-1 study. AEs were generally manageable and reversible per protocol guidelines. Three patients (7.5%) were discontinued due to treatment-related AEs (1 ...

7. esmoopen.com esmoopen.com/article/S2059-7029(24)01415-7/fulltext

Safety and clinical activity of durvalumab combined with ... In this phase I study, durvalumab, a PD-L1 inhibitor, plus tremelimumab, a CTLA-4 inhibitor, was well tolerated and safe.

8. imfinzihcp.com imfinzihcp.com/hcc/unresectable/safety.html

Safety Profile of IMFINZI® (durvalumab) & IMJUDO® ... Fatal adverse reactions occurred in 8% of patients who received IMFINZI and IMJUDO, including death (1%), hemorrhage intracranial (0.5%), cardiac arrest (0.5%), ...