Chemotherapy for Mesothelioma

Recruiting at 13 trial locations

Overseen By Michael Offin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Platinum chemotherapy

Disqualifiers: Pregnancy, Hypertension, Heart disease, 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

Duration: 12-18 weeks

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best method for administering chemotherapy to patients with malignant peritoneal mesothelioma, a rare cancer affecting the abdominal lining. Researchers compare two methods: delivering the drugs intravenously versus placing them intraperitoneally after tumor-removal surgery. Individuals diagnosed with this cancer and planning surgery to remove the disease may be suitable for the trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking an oral medication that cannot be substituted and must be held for up to ten days, it may be considered an unacceptable risk by the investigator.

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

Research has shown that the combination of pemetrexed and cisplatin, administered either intravenously or directly into the abdomen, is generally well-tolerated. Studies have found this combination to be safe, with many patients experiencing only mild side effects.

Similarly, when pemetrexed is combined with carboplatin, it is also considered safe. Research indicates it works well and is tolerated even by older patients.

These findings are based on previous studies, demonstrating that these treatment combinations have been tested in people before. The results suggest they are relatively safe options for those considering joining a clinical trial for mesothelioma treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for mesothelioma because they offer innovative ways to deliver chemotherapy. The IVC arm uses a combination of pemetrexed and cisplatin, with the option to substitute carboplatin if the patient has certain health issues, which allows for more personalized care. Meanwhile, the NIPC arm introduces a unique delivery method where chemotherapy is administered directly into the abdominal cavity through a catheter after a hyperthermic intraperitoneal chemotherapy procedure. This approach could potentially improve the effectiveness of the drugs by targeting the cancer cells more directly, possibly leading to better outcomes compared to standard intravenous chemotherapy.

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

Research has shown that using pemetrexed with cisplatin effectively treats certain cancers, such as mesothelioma. One study demonstrated that this combination extended patient survival to an average of 12.1 months, compared to 9.3 months for those using only cisplatin. Another study found that 32.5% of patients experienced tumor shrinkage or halted tumor growth. In this trial, participants in the IVC arm will receive pemetrexed and cisplatin intravenously, with carboplatin as a substitution option for those with pre-existing conditions. Meanwhile, the NIPC arm involves administering pemetrexed and either cisplatin or carboplatin through an intraperitoneal port. For patients unable to use cisplatin, combining pemetrexed with carboplatin is also effective, with over 60% of patients surviving for at least a year. These treatments target and kill fast-growing cancer cells, helping to slow or stop the disease from spreading. ^{2 5 6 7 8}

Who Is on the Research Team?

Garrett Nash, MD, MPH

Principal Investigator

Memorial Sloan Kettering Cancer

Are You a Good Fit for This Trial?

This trial is for adults with malignant peritoneal mesothelioma who've had surgery to remove most of the cancer. They need good liver and kidney function, no severe unrelated medical issues, not pregnant or breastfeeding, and can't have used certain chemotherapies before.

Inclusion Criteria

My liver functions well, with bilirubin levels within the normal range.

I agree to use reliable barrier contraception throughout the study.

I am fully active and can carry on all my pre-disease activities without restriction.

Exclusion Criteria

My blood pressure is higher than 140/90 and I'm not cleared for surgery.

I am currently pregnant or breastfeeding.

My biopsy shows I have a specific type of mesothelioma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cytoreductive Surgery and HIPEC

Participants undergo cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy

1-2 weeks

Treatment

Participants receive either intravenous or intraperitoneal chemotherapy. Intravenous chemotherapy involves 4 to 6 cycles of pemetrexed and cisplatin, while intraperitoneal chemotherapy involves administration through an intraperitoneal port.

12-18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Pemetrexed

Trial Overview

The study tests if chemotherapy given directly into the abdomen (intraperitoneal) or through a vein (intravenous) after surgery helps patients more. It compares these two methods post-surgery to see which one might be more effective.

How Is the Trial Designed?

Group I: IVC arm Experimental Treatment 3 Interventions

Pemetrexed and cisplatin will be administered intravenously for a total of 4 to 6 cycles. Participants will receive 4 cycles, but can receive up to 6 cycles based on clinician discretion. Substitution with carboplatin allowed for pre-existing impairment of hearing, renal function, or neuropathy.

Group II: NIPC arm Active Control 3 Interventions

After completion of hyperthermic intraperitoneal chemotherapy/HIPEC, an intraperitoneal catheter with a subcutaneous reservoir will be inserted through the abdominal wall. When the participant's condition is considered stable by the physicians, the NIPC will be started. Pemetrexed and either cisplatin or carboplatin will be administered through the intraperitoneal port.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

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]

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 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]

The first-line chemotherapy for locally advanced or metastatic mesothelioma is a combination of cisplatin and pemetrexed, which has been shown to be effective since its approval in 2004.

Recent studies involving nearly 200 patients indicate that combinations of anti-metabolites like gemcitabine with platinum salts can lead to a one-year survival rate of about 50%, highlighting their potential as promising treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mesothelioma: advances in chemotherapy]. Jacoulet, P.[2007]

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 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 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 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]

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