Surgery + Chemotherapy + IMRT for Mesothelioma

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

65 Participants Needed

Trial Summary

What is the purpose of this trial?

For patients with this type of cancer, the standard of care is treatment with chemotherapy. Radiation therapy is typically not used. This is because radiation to the entire lining of the lung has many side effects that are often severe including damage to the lung (pneumonitis). There is a new radiation technique using Intensity Modulated Radiation Therapy (IMRT) that has been shown to reduce many of the side effects of standard radiation therapy. This type of radiation therapy specifically targets the lining of the lung, where you have your cancer, and reduces the risk of damaging the lung itself. The purpose of this study is to test the safety and implementation of standard pleurectomy/decortication (removal of the surface lining of the lung) and standard chemotherapy followed by IMRT performed at other centers. Patients will undergo pleurectomy/decortication chemotherapy and hemithoracic pleural IMRT to the pleura in patients with malignant pleural mesothelioma.

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 the combination of surgery, chemotherapy, and IMRT safe for treating mesothelioma?

The combination of pemetrexed with cisplatin or carboplatin has been studied for safety in patients with malignant pleural mesothelioma. Common side effects include low blood cell counts, fatigue, nausea, and vomiting. Patients are advised to take folic acid and vitamin B12 to reduce severe side effects. ^{1 2 3 4 5}

What makes the Surgery + Chemotherapy + IMRT treatment for mesothelioma unique?

This treatment is unique because it combines surgery, chemotherapy, and radiation, specifically using carboplatin and pemetrexed, which has shown to be effective and well-tolerated, offering an alternative to the standard cisplatin plus pemetrexed regimen. The approach aims for a complete resection, allowing for better assessment of the cancer and potentially improving outcomes. ^{2 6 7 8 9}

What data supports the effectiveness of the drug combination of pemetrexed and platinum analogs (cisplatin or carboplatin) for treating malignant pleural mesothelioma?

Research shows that combining pemetrexed with cisplatin improves median survival from 9.3 to 12.1 months compared to cisplatin alone. Additionally, studies indicate that pemetrexed, alone or with platinum drugs, is effective and safe for treating malignant pleural mesothelioma, with better outcomes for patients who have not received prior treatment. ^{4 7 10 11 12}

Research Team

Charles Simone, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

Patients with serious unstable medical illness

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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 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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Overview on ongoing or planned clinical trials in Europe. [2015]

2. France pubmed.ncbi.nlm.nih.gov

[Investigation of allergic reactions to platinum salts]. [2019]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany. [2015]

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

Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: pemetrexed (Alimta). [2022]

7. 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]

8. 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]

9. Greece pubmed.ncbi.nlm.nih.gov

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

10. 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]

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

Gemcitabine combined with carboplatin in patients with malignant pleural mesothelioma: a multicentric phase II study. [2022]

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

Multimodality therapy in mesothelioma: role of chemotherapy. [2007]