Surgery + Chemotherapy + IMRT for Mesothelioma

Not currently recruiting at 15 trial locations

Overseen By Andreas Rimner, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Antibiotics, Antivirals, Antifungals

Disqualifiers: Sarcomatoid histology, Oxygen use, 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: Unknown

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, a cancer affecting the lung lining. It combines surgery, chemotherapy (including drugs like Carboplatin, Cisplatin, and Pemetrexed), and a newer form of radiation called Intensity Modulated Radiation Therapy (IMRT), which targets cancer cells more precisely and reduces side effects. The trial aims to determine if this combination is safe and effective for patients, particularly those with mesothelioma stages I-III that has not spread beyond the lungs. This trial may suit individuals diagnosed with these specific stages of mesothelioma. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have an active infection requiring treatment, you may not be eligible to participate.

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

Research shows that pleurectomy/decortication, a surgery to remove the lung lining, is generally well-tolerated and can help patients with malignant pleural mesothelioma live longer and feel better. Studies have found it to be a safe option when combined with other treatments.

For chemotherapy, the drugs carboplatin and cisplatin treat this cancer. Extensive research has shown them to be safe, although they can cause side effects like nausea or tiredness. Pemetrexed is often used with these drugs and is also considered safe, with similar mild side effects.

Intensity Modulated Radiation Therapy (IMRT) is a newer type of radiation treatment. It targets the cancer more precisely, reducing side effects compared to traditional radiation methods. Research suggests that IMRT is safe and can lower the risk of harming healthy lung tissue.

In summary, while these treatments can have side effects, studies show they are generally well-tolerated and safe for treating malignant pleural mesothelioma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment approach for malignant pleural mesothelioma because it combines surgery, chemotherapy, and Intensity Modulated Radiation Therapy (IMRT), offering a multi-pronged attack against the cancer. Unlike standard treatments, which typically focus on chemotherapy or surgery alone, this regimen aims for a macroscopic complete resection (MCR) of the tumor through pleurectomy/decortication, enhancing the potential effectiveness of adjuvant therapies. The use of IMRT specifically targets the pleura with precision, possibly minimizing damage to surrounding healthy tissue and reducing side effects. This comprehensive strategy may improve outcomes and offer new hope for patients battling this aggressive disease.

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

This trial will evaluate the combination of pleurectomy/decortication (P/D), chemotherapy, and Intensity Modulated Radiation Therapy (IMRT) for treating malignant pleural mesothelioma. Research has shown that P/D, which removes the lining of the lung, yields promising results, with patients typically living about 34 months on average, and some living more than five years. In this trial, chemotherapy drugs like carboplatin and cisplatin, often used with pemetrexed, will be administered either before or after P/D. These drugs proved effective in previous studies, with patients living up to 26.7 months on average. IMRT, a precise type of radiation treatment, is generally well-tolerated and has led to a two-year survival rate of 36% in some studies. These treatments, as part of this trial, work together to manage the disease and may help extend life. ^{2 3 4 6 7}

Who Is on the Research Team?

Charles Simone, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with stage I-III malignant pleural mesothelioma, specifically epithelioid or biphasic subtypes. Participants must have good physical function and adequate organ function as shown by specific blood tests. Pregnant women, those with active infections requiring treatment, other cancers, serious illnesses, continuous oxygen use, or prior treatments like intrapleural therapy are excluded.

Inclusion Criteria

My organs are functioning well according to my recent lab tests.

My lung function test shows at least 35% efficiency.

The amount of bilirubin in your blood is not too high.

Exclusion Criteria

My cancer has more than 10% sarcomatoid or desmoplastic features.

Patients with serious unstable medical illness

I have had treatments directly in my chest cavity, except for pleurodesis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo pleurectomy/decortication with the goal of a macroscopic complete resection

1-2 weeks

Chemotherapy

Participants receive standard chemotherapy, which may be administered in the neoadjuvant setting prior to surgery

6-12 weeks

Radiation

Participants receive Intensity Modulated Radiation Therapy (IMRT) to the pleura

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment for pneumonitis

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Intensity Modulated Radiation Therapy
• Pemetrexed
• Pleurectomy/Decortication

Trial Overview The study investigates the safety and effectiveness of combining surgery (pleurectomy/decortication), standard chemotherapy (pemetrexed with cisplatin or carboplatin), followed by a targeted radiation technique called IMRT that aims to minimize lung damage in patients with malignant pleural mesothelioma.

How Is the Trial Designed?

Group I: 1 Experimental Treatment 3 Interventions

This is a multicenter phase II toxicity study of pleurectomy/decortication (P/D) followed by adjuvant chemotherapy and Intensity Modulated Radiation Therapy (IMRT) to the pleura in patients with malignant pleural mesothelioma. Alternatively, chemotherapy may be administered in the neoadjuvant setting prior to P/D, followed by IMRT. Patients deemed resectable at the time of enrollment will undergo P/D with the goal of a macroscopic complete resection (MCR). Those with disease progression or severe toxicity will stop chemotherapy and undergo a PET scan.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Brigham and Women's Hospital

Collaborator

Trials

1,694

Recruited

14,790,000+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

Princess Margaret Hospital, Canada

Collaborator

Trials

121

Recruited

40,000+

Published Research Related to This Trial

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]

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 II clinical study involving 102 patients with malignant pleural mesothelioma, the combination of pemetrexed and carboplatin resulted in an objective response rate of 18.6%, with 65.7% of patients achieving disease control.

The treatment was well tolerated, with mild toxicity reported; grade 3 or 4 neutropenia occurred in 9.7% of cycles, and the median overall survival was 12.7 months, suggesting that this combination could be a viable alternative to the standard treatment with pemetrexed and cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. Ceresoli, GL., Zucali, PA., Favaretto, AG., et al.[2022]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33769073/

Treatment patterns and outcomes of patients with ... Pemetrexed + cisplatin or pemetrexed + carboplatin was shown to be the most common treatment received by patients when first diagnosed with advanced MPM.

2. ilcn.org ilcn.org/real-world-data-show-that-survival-just-as-good-with-carboplatin-therapy-as-with-cisplatin-therapy-in-malignant-pleural-mesothelioma/

Real-World Data Show That Survival Just as Good With ... The largest real-world cohort study of individuals with malignant pleural mesothelioma (MPM) found a median survival duration of 8 months ...

3. nature.com nature.com/articles/s41598-021-00831-4

Efficacy of chemotherapy for malignant pleural ... For patients who received carboplatin plus pemetrexed in first line the median OS was 26.7 months in epithelioid versus 14.8 months in non- ...

4. jto.org jto.org/article/S1556-0864(15)32118-3/fulltext

Treatment of Malignant Pleural Mesothelioma with ... Toxicity was fairly low. There were 56 responses (32.4%), of which 2 were complete; the median time to progression was 8.6 months, and the median overall ...

5. tandfonline.com tandfonline.com/doi/full/10.2217/fon-2021-0047

Full article: Treatment Patterns and Outcomes of Patients ... Median overall survival for first-line SACT was 12.0 months (95% CI: 10.7–14.2). Results were similar with pemetrexed + cisplatin and pemetrexed + carboplatin.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/18978569/

Treatment of malignant pleural mesothelioma with ... There were 56 responses (32.4%), of which 2 were complete; the median time to progression was 8.6 months, and the median overall survival was 13 months. Some ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S155608642100349X

OA09.05 Real-World Survival Outcomes of Patients with ... This study included 735 patients with MPM, 68% had asbestos exposure, and 59% had epithelioid histology. More patients were treated with carboplatin (n=434) ...