RMT + Immunotherapy + Chemotherapy for Lung Cancer

Overseen By Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Masonic Cancer Center, University of Minnesota

Must not be taking: Immunosuppressants, Probiotics

Disqualifiers: Pregnancy, Autoimmune disease, Active infection, 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: 2 years

82 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized, active-controlled, parallel-group, double-blind Phase II trial, of oral restorative microbiota therapy (RMT) or placebo combined with intravenous (IV) durvalumab (MEDI4736) plus chemotherapy in patients with treatment naïve advanced or metastatic adenocarcinoma non-small cell lung cancer (NSCLC)

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on daily probiotics or chronic systemic antibiotics. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination of Cisplatin/pemetrexed or Carboplatin/pemetrexed for lung cancer?

Research shows that pemetrexed, when combined with cisplatin or carboplatin, has demonstrated significant antitumor activity in non-small cell lung cancer (NSCLC) with manageable side effects, especially when supplemented with folic acid and vitamin B12 to reduce toxicity. ^{1 2 3 4 5}

Is the combination of pemetrexed and cisplatin safe for humans?

Pemetrexed combined with cisplatin has been approved for use in certain cancers and is generally considered safe when patients receive vitamin supplements to reduce side effects. Common side effects include low blood cell counts, fatigue, and nausea, but these can be managed with proper medical care. ^{1 3 6 7 8}

What makes the RMT + Immunotherapy + Chemotherapy treatment for lung cancer unique?

This treatment is unique because it combines traditional chemotherapy with immunotherapy (Durvalumab) and an innovative approach using Oral Restorative Microbiota Therapy (RMT) Capsules, which may enhance the body's immune response and improve treatment outcomes. ^{1 3 4 9 10}

Research Team

Amit Kulkarni, MBBS

Principal Investigator

University of Minnesota, Division of Hematology, Oncology and Transplantation

Eligibility Criteria

This trial is for adults with advanced or metastatic lung adenocarcinoma that can't be surgically removed and doesn't have certain genetic mutations. They must weigh over 30 kg, have a performance status of 0 or 1, agree to use contraception if applicable, and not have had recent major surgery or other treatments that might interfere. Those with stable treated brain metastases may qualify.

Inclusion Criteria

Provide voluntary written consent prior to the performance of any research related tests or procedures

My lung cancer is advanced, cannot be surgically removed, and lacks certain genetic changes.

My body weight is over 30 kg.

Exclusion Criteria

I have not had a heart attack or stroke in the last 3 months.

I have had lung inflammation or lung disease that needed steroids.

I haven't taken strong immune system suppressing drugs in the last 28 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

10 patients are enrolled in this safety run-in arm. Patients are directly assigned to RMT treatment arm. After safety run-in period of 4 weeks after the first dose of RMT, if no new safety signals are seen, enrollment moves to randomization.

4 weeks

Treatment

Participants receive oral restorative microbiota therapy (RMT) or placebo combined with intravenous (IV) durvalumab plus chemotherapy.

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and overall survival.

3 years

Treatment Details

Interventions

• Cisplatin/pemetrexed or Carboplatin/pemetrexed
• Durvalumab 1500 mg IV
• Oral Restorative Microbiota Therapy (RMT) Capsules

Trial Overview The study tests oral RMT capsules versus placebo combined with IV Durvalumab and chemo (Cisplatin/Pemetrexed or Carboplatin/Pemetrexed). It's a Phase II trial where patients are randomly assigned to either the RMT group or the placebo group while receiving standard cancer treatment.

Participant Groups

Group I: Safety Run-in Experimental Treatment 3 Interventions

10 patients are enrolled in this safety run-in arm. Patients are directly assigned to RMT treatment arm. After safety- run-in period of 4 weeks after the first dose of RMT, in the 10 patients if no new safety signal are seen enrollment moves to randomization

Group II: Arm B (Placebo) Experimental Treatment 3 Interventions

Group III: Arm A (RMT) Experimental Treatment 3 Interventions

Cisplatin/pemetrexed or Carboplatin/pemetrexed is already approved in United States, European Union for the following indications:

Approved in United States as Cisplatin/Pemetrexed for:

• Non-small cell lung cancer (NSCLC)
• Mesothelioma
• Ovarian cancer
• Testicular cancer

Approved in United States as Carboplatin/Pemetrexed for:

• Non-small cell lung cancer (NSCLC)
• Mesothelioma
• Ovarian cancer

Approved in European Union as Cisplatin/Pemetrexed for:

• Non-small cell lung cancer (NSCLC)
• Mesothelioma
• Ovarian cancer
• Testicular cancer

Approved in European Union as Carboplatin/Pemetrexed for:

• Non-small cell lung cancer (NSCLC)
• Mesothelioma
• Ovarian cancer

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Findings from Research

Pemetrexed, a multitargeted antifolate approved for certain cancers, has shown promising activity against various other tumors, including gastrointestinal, breast, and bladder cancers, indicating its potential as a broader treatment option.

The drug has a favorable tolerability profile, especially after the introduction of folic acid and vitamin B12 supplementation, suggesting that higher doses could be safely used in clinical practice, which may enhance its efficacy in treating advanced gastrointestinal tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role of pemetrexed in gastrointestinal cancer. Meriggi, F., Di Biasi, B., Caliolo, C., et al.[2015]

Pemetrexed is an effective anticancer drug that works by inhibiting enzymes necessary for DNA and RNA production, and its toxic side effects can be significantly reduced with folic acid and vitamin B12 supplementation.

Phase III studies have confirmed pemetrexed's role in treating non-small cell lung cancer and malignant pleural mesothelioma, and it has shown promise in various other cancers, including colorectal and breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical activity of pemetrexed: a multitargeted antifolate anticancer agent. Solomon, B., Bunn, PA.[2015]

The study identified that NCI-H460/PMT cells, which are resistant to the drug pemetrexed (PMT), showed increased expression of Thymidylate Synthase (TYMS), suggesting that TYMS overexpression is a key mechanism behind PMT resistance in these lung cancer cells.

Additionally, the resistant cells exhibited cross-resistance to other chemotherapy drugs, indicating that the mechanisms of resistance may extend beyond just PMT, complicating treatment strategies for patients with Non-Small Cell Lung Cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment and Characterization of Pemetrexed-resistant NCI-H460/PMT Cells. Xu, YL., Jiang, XM., Zhang, LL., et al.[2020]

Pemetrexed is a multitargeted antifolate that effectively inhibits key enzymes in the folate pathway, showing clinical activity in non-small-cell lung cancer (NSCLC) and various other solid tumors.

The addition of low-level folic acid and vitamin B12 supplements enhances the safety of pemetrexed treatment without reducing its effectiveness against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. Molina, JR., Adjei, AA.[2015]

Pemetrexed, when combined with carboplatin, has shown promising antitumor activity with mild toxicity in phase II clinical trials, but it can lead to serious adverse reactions such as toxic epidermal necrolysis, as seen in a reported case.

Supplementation with folic acid and vitamin B12 is recommended during pemetrexed treatment to help reduce the risk of hematological and gastrointestinal side effects, although severe skin reactions can still occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis related to pemetrexed and carboplatin with vitamin B12 and folic acid supplementation for advanced non-small cell lung cancer. Bosch-Barrera, J., Gaztañaga, M., Ceballos, J., et al.[2015]

Pemetrexed remains chemically stable for up to 2 days at room temperature and 31 days when refrigerated, indicating it can be safely stored for these durations in dextrose 5% injection and NaCl 0.9% injection.

However, significant microparticulate formation occurs in pemetrexed solutions stored in PVC bags beyond 24 hours in refrigeration, suggesting that to ensure safety and efficacy, storage should be limited to the manufacturer's recommended 24-hour period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical and chemical stability of pemetrexed in infusion solutions. Zhang, Y., Trissel, LA.[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]

Pemetrexed, a multi-targeted antifolate chemotherapy agent, has shown superior survival rates and response compared to cisplatin alone in patients with malignant pleural mesothelioma when used in combination with cisplatin and vitamin supplementation.

In patients with advanced NSCLC, pemetrexed demonstrated similar efficacy to docetaxel but with significantly fewer severe side effects, making it a safer option, especially for high-risk patients like the elderly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pemetrexed]. Sudoh, J., Gemma, A.[2015]

Pemetrexed is an effective antimetabolite that targets key enzymes in the folate pathway and has shown clinical activity in various cancers, particularly non-small cell lung cancer, in both first- and second-line treatment settings.

Supplementing with low doses of folic acid and vitamin B12 can reduce the toxicity of pemetrexed on mucosal and bone marrow tissues while maintaining its effectiveness against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed (ALIMTA), a novel multitargeted antineoplastic agent. Adjei, AA.[2015]

In a phase III trial involving 657 patients with advanced EGFR-mutated non-small-cell lung cancer, both amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy significantly improved progression-free survival (PFS) compared to standard chemotherapy, with median PFS of 6.3 and 8.3 months versus 4.2 months, respectively.

The combination therapies also showed a higher objective response rate (64% and 63% for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively) compared to chemotherapy (36%), although the amivantamab-lazertinib-chemotherapy regimen had more hematologic adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Passaro, A., Wang, J., Wang, Y., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

The potential role of pemetrexed in gastrointestinal cancer. [2015]

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

Clinical activity of pemetrexed: a multitargeted antifolate anticancer agent. [2015]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Establishment and Characterization of Pemetrexed-resistant NCI-H460/PMT Cells. [2020]

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

The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. [2015]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis related to pemetrexed and carboplatin with vitamin B12 and folic acid supplementation for advanced non-small cell lung cancer. [2015]

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

Physical and chemical stability of pemetrexed in infusion solutions. [2022]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Japan pubmed.ncbi.nlm.nih.gov

[Pemetrexed]. [2015]

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

Pemetrexed (ALIMTA), a novel multitargeted antineoplastic agent. [2015]

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

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. [2023]