Methoxyamine + Chemotherapy for Mesothelioma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well the new drug methoxyamine works with chemotherapy drugs cisplatin and pemetrexed disodium to treat advanced mesothelioma, a cancer affecting the lining of the lungs or abdomen. The trial aims to determine the best dose, monitor side effects, and assess whether this combination can shrink tumors or increase their sensitivity to treatment. This trial may suit individuals whose mesothelioma has not responded to standard treatments and who can swallow pills. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new drug combination.

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.

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

Research shows that methoxyamine, when combined with pemetrexed disodium, is generally well-tolerated by patients with mesothelioma. This combination has shown promise for patients whose cancer has continued to grow despite previous pemetrexed treatments. Some patients have experienced side effects, but these are usually manageable.

Additionally, researchers have studied the combination of methoxyamine, pemetrexed disodium, and cisplatin to determine the right dose and understand the side effects. This treatment has been administered to patients with advanced tumors, and while side effects can occur, they are generally manageable.

These findings come from early-stage research, which mainly focuses on safety and patient tolerance. Trials are carefully monitoring patient reactions, and safety data is still being collected. However, current results are encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for mesothelioma because they incorporate methoxyamine, a unique addition to the typical chemotherapy regimen. Unlike the standard treatment that primarily uses pemetrexed disodium and cisplatin, these investigational arms introduce methoxyamine, which targets a different aspect of cancer cell repair. Methoxyamine works by blocking the repair of DNA damage in cancer cells, enhancing the effectiveness of chemotherapy drugs. This dual-action approach could potentially improve outcomes by making cancer cells more susceptible to the effects of chemotherapy.

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

Research shows that methoxyamine can increase the sensitivity of cancer cells to chemotherapy drugs like cisplatin and pemetrexed disodium. In this trial, participants in Arm A will receive methoxyamine with both pemetrexed disodium and cisplatin, while those in Arm B will receive methoxyamine with pemetrexed disodium only. Studies have found that combining methoxyamine with these drugs may shrink tumors in people with mesothelioma or other advanced solid tumors. Methoxyamine works by disrupting a repair process in cancer cells, potentially enhancing the effectiveness of chemotherapy. Patients who have tried this combination have generally tolerated it well, with some experiencing reduced tumor growth. This approach aims to improve outcomes for those whose cancer hasn't responded to standard treatments. ^{1 2 4 5 6}

Who Is on the Research Team?

Marianna Koczywas

Principal Investigator

City of Hope Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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 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 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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02535312?cond=%22Peritoneal%20Mesothelioma%22&intr=%22Pemetrexed%22&viewType=Table&rank=5

Methoxyamine, Cisplatin, and Pemetrexed Disodium in ... 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 ...

2. withpower.com withpower.com/trial/methoxyamine-chemotherapy-for-mesothelioma-cae84

Methoxyamine + Chemotherapy for Mesothelioma ... Methoxyamine and Pemetrexed Disodium will have tolerable side effects & efficacy for patients with Malignant Pleural Mesothelioma, Peritoneal Mesothelioma ...

3. clinconnect.io clinconnect.io/trials/NCT02535312

Methoxyamine, Cisplatin, and Pemetrexed Disodium in This clinical trial is testing a combination of three drugs—methoxyamine, cisplatin, and pemetrexed disodium—to see how well they can treat patients with ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT301651

Phase I study of TRC102 in combination with cisplatin and ... Phase I study of TRC102 in combination with cisplatin and pemetrexed in patients with advanced solid tumors/Phase II study of TRC102 with pemetrexed in patients ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02535312?term=pemetrexed&rank=6&tab=results

Study Results | Methoxyamine, Cisplatin, and Pemetrexed ... A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.

6. sigma.larvol.com sigma.larvol.com/product.php?e1=415037&tab=newstrac&page=2

methoxyamine (TRC102) News The combination of TRC102 and pemetrexed demonstrated activity in malignant mesothelioma that progressed on prior pemetrexed. Additional studies are warranted ...