Methoxyamine + Chemotherapy for Mesothelioma

Recruiting at 17 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Steroids, Antiseizure

Disqualifiers: Active brain metastases, HIV, others

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

Compensation: Varies

Number of Visits: 8

Duration: 18 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I/II trial studies the side effects and the best dose of methoxyamine when given together with cisplatin and pemetrexed disodium and to see how well it works in treating patients with solid tumors or mesothelioma that have spread to other places in the body and usually cannot be cured or controlled with standard treatment (advanced), or mesothelioma that does not respond to pemetrexed disodium and cisplatin or carboplatin (refractory). Methoxyamine may shrink the tumor and may also help cisplatin and pemetrexed disodium work better by making tumor cells more sensitive to the drugs. Drugs used in chemotherapy, such as cisplatin and pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving methoxyamine together with cisplatin and pemetrexed disodium may be a better treatment for solid tumors or mesothelioma than methoxyamine and pemetrexed disodium.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you should inform your doctor about all medications, including over-the-counter and herbal products, as there may be interactions with the trial drugs.

What data supports the effectiveness of the drug combination Methoxyamine and Chemotherapy for Mesothelioma?

Research shows that the combination of pemetrexed and cisplatin, which are part of the chemotherapy regimen, has been effective in treating malignant pleural mesothelioma, improving survival from 9.3 to 12.1 months compared to cisplatin alone. Pemetrexed is a key drug in mesothelioma treatment, often used with platinum-based drugs like cisplatin. ^{1 2 3 4 5}

Is the combination of methoxyamine and chemotherapy safe for treating mesothelioma?

The combination of pemetrexed and cisplatin, which is used for treating mesothelioma, has been studied for safety. 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, and corticosteroids to prevent skin rashes. ^{1 6 7 8 9}

What makes the drug combination of Methoxyamine, Cisplatin, and Pemetrexed unique for treating mesothelioma?

This drug combination is unique because it includes Methoxyamine, which is being studied for its potential to enhance the effectiveness of chemotherapy by interfering with the cancer cells' ability to repair DNA damage. Pemetrexed combined with Cisplatin has already shown improved survival rates in mesothelioma patients compared to Cisplatin alone, and the addition of Methoxyamine could potentially increase this benefit. ^{3 4 5 10 11}

Research Team

Marianna Koczywas

Principal Investigator

City of Hope Comprehensive Cancer Center LAO

Eligibility Criteria

This trial is for patients with advanced solid tumors or mesothelioma that's spread and can't be cured or controlled with standard treatment, or those whose mesothelioma didn't respond to specific chemotherapy. Participants must have good organ function, limited prior chemotherapy treatments, and a life expectancy over 3 months. They should not be pregnant, breastfeeding, have severe illnesses affecting study compliance, excessive previous cisplatin doses, hemolysis disorders, active brain metastases requiring steroids or antiseizure meds.

Inclusion Criteria

I can swallow pills on my own without needing a tube.

You have enough infection-fighting white blood cells in your body.

My advanced cancer has no standard treatment left, or I can receive cisplatin with pemetrexed.

Exclusion Criteria

You are currently taking any other experimental medications.

There is not enough information about how TRC102 might interact with other medications. If you join the study, you will be told about the risks of mixing TRC102 with other drugs, and what to do if you need to take new prescriptions, over-the-counter medications, or herbal products. The study will keep track of all the medications and treatments you use while participating.

I have received more than 300 mg/m^2 of cisplatin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive methoxyamine, pemetrexed disodium, and cisplatin in cycles of 21 days for up to 6 cycles

18 weeks

6 cycles, each with 1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

2 visits (in-person)

Open-label extension (optional)

Participants may continue methoxyamine and pemetrexed disodium beyond cycle 6 if they continue to benefit from treatment

Long-term

Treatment Details

Interventions

• Cisplatin
• Methoxyamine
• Pemetrexed Disodium

Trial Overview The trial tests methoxyamine combined with cisplatin and pemetrexed disodium to see if it's more effective for treating these cancers than the current standard of care. Methoxyamine might make cancer cells more sensitive to the other drugs. The study will determine the best dose of methoxyamine and evaluate how well this combination works in shrinking tumors.

Participant Groups

Group I: Arm B (methoxyamine, pemetrexed disodium) Experimental Treatment 2 Interventions

Patients receive methoxyamine PO QD on days 1-4 and pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue methoxyamine and pemetrexed disodium beyond cycle 6 if the patient continues to benefit from treatment at the discretion of the treating physician.

Group II: Arm A (methoxyamine, pemetrexed disodium, cisplatin) Experimental Treatment 3 Interventions

Patients receive methoxyamine PO QD on days 1-4, pemetrexed disodium IV over 10 minutes, and cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue methoxyamine and pemetrexed disodium beyond cycle 6 if the patient continues to benefit from treatment at the discretion of the treating physician.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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 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]

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 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]

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]

The combination of pemetrexed and carboplatin as first-line chemotherapy for malignant pleural mesothelioma showed a moderate overall response rate of 25% among 76 patients, with 21% achieving partial responses and 4% complete responses.

While the treatment was associated with some toxicity, with 47.3% of patients experiencing grade 3 hematological toxicity, the overall safety profile was considered acceptable, and the median survival for patients was estimated at 14 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). Castagneto, B., Botta, M., Aitini, E., et al.[2020]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

3. Ireland pubmed.ncbi.nlm.nih.gov

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

4. France pubmed.ncbi.nlm.nih.gov

Pemetrexed: new drug. Pleural mesothelioma: a first encouraging trial. [2013]

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

Pemetrexed for diffuse malignant pleural mesothelioma. [2019]

6. Ireland pubmed.ncbi.nlm.nih.gov

Carboplatin and pemetrexed in the management of malignant pleural mesothelioma: a realistic treatment option? [2015]

7. 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]

8. England 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). [2020]

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

A review of chemotherapy trials for malignant mesothelioma. [2019]