Pembrolizumab + Chemotherapy for Mesothelioma

Overseen By Corey Langer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Abramson Cancer Center of the University of Pennsylvania

Must not be taking: Immunosuppressants, Steroids, Monoclonal antibodies, others

Disqualifiers: Immunodeficiency, Active TB, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 1 year

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for malignant pleural mesothelioma (MPM), a serious cancer affecting the lung lining. The study combines pembrolizumab, an immunotherapy that helps the immune system fight cancer, with chemotherapy (including drugs like cisplatin and pemetrexed) and surgery. The main goal is to evaluate the safety and effectiveness of this combination. Individuals with MPM who have measurable tumors and are willing to undergo surgery and chemotherapy may be suitable candidates for this trial. 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 new combination therapy.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot be on immunosuppressive therapy or chronic systemic steroids above a certain dose, and you must not have had recent chemotherapy, targeted therapy, or radiation therapy within 2 weeks before starting the trial.

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

Research has shown that pembrolizumab, combined with the chemotherapy drugs cisplatin and pemetrexed, has been tested for safety and effectiveness. One study found that this combination helped patients live longer compared to chemotherapy alone, indicating it is generally well-tolerated.

Another study examined safety and found that using pembrolizumab with cisplatin and pemetrexed was safe and manageable. Some patients experienced side effects, such as tiredness and nausea, which are common with cancer treatments. The FDA has already approved these drugs for treating other types of cancer, adding reassurance about their safety.

Overall, current evidence suggests that the treatment is safe, but individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab, cisplatin, and pemetrexed for mesothelioma because it offers a novel approach by incorporating an immunotherapy agent. Unlike traditional treatments that primarily rely on chemotherapy to attack cancer cells directly, pembrolizumab is an immunotherapy drug that helps the immune system recognize and fight cancer cells more effectively. This combination could potentially enhance the effectiveness of chemotherapy while offering a new mechanism of action to tackle mesothelioma, a cancer known for its resistance to conventional treatments. By integrating pembrolizumab, this approach aims to improve patient outcomes by engaging the body's natural defenses.

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

Research shows that combining pembrolizumab with chemotherapy extends the lives of patients with malignant pleural mesothelioma (MPM). In this trial, participants will receive pembrolizumab alongside image-guided surgery and chemotherapy. Studies have found that patients receiving both pembrolizumab and chemotherapy lived longer than those receiving only chemotherapy. Additionally, cisplatin proves more effective when combined with pemetrexed than when used alone. Patients treated with both cisplatin and pemetrexed lived, on average, several months longer than those who received only cisplatin. Pemetrexed not only helps control the disease but also reduces symptoms like chest pain and shortness of breath. Together, these treatments offer hope for improving survival and quality of life for people with MPM. ^{6 7 8 9 10}

Who Is on the Research Team?

Corey Langer, MD

Principal Investigator

University of Pennsylvania Abramson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with malignant pleural mesothelioma who are in good physical condition, have proper organ function, and can provide a recent tumor tissue sample. They must not have other active cancers or serious health conditions that could interfere with the study, no recent immunosuppressive treatments, and agree to use contraception.

Inclusion Criteria

I agree to provide a recent biopsy sample or an archived one with approval.

I can carry out all my usual activities without help.

I agree to use or continue using contraception during and up to 120 days after the study.

Exclusion Criteria

I have been diagnosed with interstitial lung disease.

I have had pneumonitis treated with steroids or have it now.

Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab in combination with chemotherapy and undergo image-guided surgery

up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days for serious adverse events

Long-term follow-up

Participants are assessed for overall survival and progression-free survival

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Indocyanine Green (ICG) Image-Guided Surgery
• Pembrolizumab
• Pemetrexed

Trial Overview

The trial tests pembrolizumab (an immune therapy) combined with chemotherapy (cisplatin and pemetrexed) and image-guided surgery using Indocyanine Green (ICG). It aims to assess safety, feasibility, and initial effectiveness of this combination treatment approach.

How Is the Trial Designed?

Group I: Pembrolizumab with image-guided surgery and chemotherapy Experimental Treatment 4 Interventions

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Published Research Related to This Trial

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]

Malignant mesothelioma is a challenging cancer to treat, and while newer agents like gemcitabine and pemetrexed show some promise, their impact on survival is minimal for patients with unresectable disease.

A phase III trial involving over 450 patients is underway to compare the effectiveness of cisplatin alone versus a combination of pemetrexed and cisplatin, with preliminary phase II results indicating a 15% partial response rate for pemetrexed alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of gemcitabine and pemetrexed (Alimta) in the management of patients with malignant mesothelioma. Green, MR.[2019]

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]

In a phase 3 trial involving 440 patients with advanced pleural mesothelioma, the addition of pembrolizumab to standard platinum-pemetrexed chemotherapy significantly improved overall survival, with a median survival of 17.3 months compared to 16.1 months for chemotherapy alone.

While the combination treatment was effective, it also led to a higher incidence of serious adverse events, with 27% of patients experiencing grade 3 or 4 adverse events compared to 15% in the chemotherapy-only group, indicating a need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. Chu, Q., Perrone, F., Greillier, L., et al.[2023]

In a phase 2 trial involving 120 patients, the combination of standard chemotherapy (platinum and pemetrexed) with pembrolizumab (CP + pembro) showed improved median survival (19.8 months) and overall response rate (47%) compared to chemotherapy alone (8.9 months and 19%, respectively).

The addition of pembrolizumab to chemotherapy was found to be tolerable, and although the progression-free survival was similar between the treatment arms, the combination therapy demonstrated better outcomes, leading to the continuation of research in a phase 3 trial with results expected in 2023.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: Canadian Cancer Trials Group IND.227: A Phase 2 Randomized Study of Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma (NCT02784171). Piccirillo, MC., Chu, Q., Bradbury, P., et al.[2023]

Pemetrexed, often combined with cisplatin or carboplatin, is the most widely studied treatment for malignant pleural mesothelioma (MPM) in Europe, with around 1500 patients enrolled in an Extended Access Program, showing improved survival rates compared to other treatments.

The largest randomized trial indicated that combining pemetrexed with cisplatin improved median survival from 9.3 to 12.1 months, highlighting its efficacy in treating MPM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview on ongoing or planned clinical trials in Europe. Favaretto, A.[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]

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 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]

The combination of pemetrexed and cisplatin has been shown to induce high response rates in malignant pleural mesothelioma (MPM), a type of lung cancer that has been resistant to chemotherapy.

The review highlights a key phase III clinical trial that led to the FDA approval of pemetrexed, indicating its significant role in the treatment of MPM, with ongoing research expected to further clarify its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of pemetrexed in combination with cisplatin for the treatment of malignant pleural mesothelioma. Goudar, RK.[2022]

Pemetrexed disodium is an effective antimetabolite that works by inhibiting key enzymes involved in tumor growth, showing a 14.5% response rate as a single agent in previously untreated mesothelioma patients.

Combining pemetrexed with cisplatin or carboplatin has resulted in promising regression rates, with a notable 40% partial response rate in a trial involving 25 mesothelioma patients, indicating enhanced efficacy when used in combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alimta (pemetrexed disodium): a multitargeted antifolate for the treatment of mesothelioma. Green, MR.[2019]

The recommended dose of pemetrexed combined with cisplatin (Pem/Cis) was established as effective for treating malignant pleural mesothelioma (MPM) in a Phase I/II study involving 19 Japanese patients, with a partial response rate of 36.8%.

The treatment showed an acceptable safety profile, although some patients experienced significant toxicities like neutropenia and one drug-related death due to worsening pneumonia, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pemetrexed in combination with cisplatin for malignant pleural mesothelioma: a phase I/II study in Japanese patients. Nakagawa, K., Yamazaki, K., Kunitoh, H., et al.[2022]

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