MTI-301 for Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: QT prolonging, CYP inhibitors

Disqualifiers: Pregnancy, HIV, Hepatitis, Cardiac, others

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

Compensation: Varies

Number of Visits: 3

Duration: 24 weeks

42 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that are known to interact with major enzymes or transporters at least 14 days before joining. If you're on these medications, you may need to stop or switch them, but the protocol doesn't specify all medications, so check with the trial team.

What data supports the effectiveness of the drug MTI-301 for cancer?

Research suggests that bevacizumab, a component of MTI-301, may enhance the effect of chemotherapy in breast cancer patients with leptomeningeal carcinomatosis by improving drug delivery to tumors. ^{1 2 3 4 5}

What safety data exists for MTI-301 or similar treatments in humans?

The safety of similar treatments has been evaluated in studies, showing that while some targeted cancer drugs can cause significant side effects, these are often manageable and rarely lead to stopping treatment completely. In some cases, doses are adjusted to reduce side effects. ^{6 7 8 9 10}

How is the drug MTI-301 different from other cancer treatments?

MTI-301 is unique because it targets the mTOR signaling pathway, which is often dysregulated in various cancers, using small molecule inhibitors. This approach aims to specifically inhibit tumor growth with potentially fewer side effects compared to traditional chemotherapy, which affects both cancerous and normal cells. ^{11 12 13 14 15}

What is the purpose of this trial?

This phase I trial tests the safety, side effects, and best dose of MTI-301 in treating patients with solid cancers that have spread from where they first started (primary site) to other places in the body (metastatic) or that cannot be removed by surgery (unresectable) and that have not responded to previous treatment (refractory). MTI-301 is a drug that inhibits an enzyme called SCD1. SCD1 is an enzyme that promotes tumor growth and spread and is upregulated in some cancer types. MTI-301 may disrupt the activity of SCD1, which may lead to reduced tumor growth and/or spread.

Research Team

Winston Tan, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for patients with solid tumors that have spread or can't be surgically removed and haven't improved after treatment. Participants must have measurable disease, acceptable organ function, and no other options of curative therapy.

Inclusion Criteria

Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria or evaluable disease

Absolute neutrophil count (ANC) ≥ 1500/mm^3 (obtained ≤ 28 days prior to registration)

Platelet count ≥ 100,000/mm^3 (obtained ≤ 28 days prior to registration)

Exclusion Criteria

Persons who are of childbearing potential who are unwilling to employ adequate contraception

Corrected QT (QTc) prolongation based on QTc interval prior to registration of ≥ 470 ms using the Fridericia's formula (QTcF)

Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MTI-301 orally once daily on days 1-28 of each cycle, with cycles repeating every 28 days for up to 6 cycles

24 weeks

Regular imaging and blood sample collection throughout the study

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

1 year

Follow-up every 3 months

Treatment Details

Interventions

• MTI-301

Trial Overview The trial tests the safety and optimal dose of MTI-301, a drug targeting SCD1—an enzyme aiding tumor growth—in patients with advanced or stubborn solid cancers. It includes scans like CT, MRI, PET, biospecimen collection, and questionnaires.

Participant Groups

Group I: Treatment (MTI-301) Experimental Treatment 6 Interventions

Patients receive MTI-301 PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, PET/CT, or MRI and collection of blood samples throughout the study, and undergo tissue sample collection at baseline and at disease progression.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a 24-week study involving 507 patients with active rheumatoid arthritis, tofacitinib dosages of 3 mg twice daily or higher significantly improved symptoms compared to placebo, with ACR20 response rates exceeding 50%.

Tofacitinib was generally well-tolerated, with manageable side effects such as diarrhea and upper respiratory infections, and showed sustained efficacy in improving various health measures over the study period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone. Kremer, JM., Cohen, S., Wilkinson, BE., et al.[2022]

The study found that an oral drug combining paclitaxel and HM30181A is well tolerated in patients with advanced cancers, with only one case of significant toxicity (grade 3 neutropenia) reported at a dose of 240 mg/m².

The recommended phase II dose for this combination therapy is 300 mg/m² of paclitaxel, which effectively achieves the desired plasma concentration for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study of Oral Paclitaxel with a Novel P-Glycoprotein Inhibitor, HM30181A, in Patients with Advanced Solid Cancer. Lee, HJ., Heo, DS., Cho, JY., et al.[2021]

In a phase I study involving 26 patients with refractory solid tumors, the combination of docetaxel and temsirolimus was limited by severe dose-limiting toxicities (DLTs), such as grade 4 neutropenia and grade 3 diarrhea, preventing the determination of a maximal tolerated dose (MTD).

The study's innovative Bayesian Optimal Interval design indicated similar DLT rates at different dose levels, but ultimately, patients could not tolerate the treatment regimen without dose reductions, suggesting that this combination should not be pursued further at the tested doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Docetaxel and Temsirolimus in Refractory Solid Tumors. Amin, M., Gao, F., Terrero, G., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

A pilot study of bevacizumab combined with etoposide and cisplatin in breast cancer patients with leptomeningeal carcinomatosis. [2022]

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

A retrospective analysis of first-line PD-1 monoclonal antibodies treatment in patients with leptomeningeal metastasis from solid tumors. [2023]

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

Treatment and prognosis of leptomeningeal disease secondary to metastatic breast cancer: A single-centre experience. [2018]

4. Singapore pubmed.ncbi.nlm.nih.gov

Bevacizumab might potentiate the chemotherapeutic effect in breast cancer patients with leptomeningeal carcinomatosis. [2017]

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

A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone. [2022]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

A Phase I Study of Oral Paclitaxel with a Novel P-Glycoprotein Inhibitor, HM30181A, in Patients with Advanced Solid Cancer. [2021]

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

Open-label, non-randomised, inter-individual dose escalation of ZK 304709 with the evaluation of safety, tolerability, pharmacokinetics, oral bioavailability and orientating efficacy after daily administration in patients with advanced cancer (7 d treatment and 14 d recovery). [2008]

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

Are Doses and Schedules of Small-Molecule Targeted Anticancer Drugs Recommended by Phase I Studies Realistic? [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

A phase I dose escalation study of the pharmacokinetics and tolerability of ZK 304709, an oral multi-targeted growth inhibitor (MTGI), in patients with advanced solid tumours. [2013]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacogenomic Markers of Targeted Therapy Toxicity in Patients with Metastatic Renal Cell Carcinoma. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Recent advances in targeting mTOR signaling pathway using small molecule inhibitors. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Inhibition of the phosphoinositide 3-kinase pathway for the treatment of patients with metastatic metaplastic breast cancer. [2020]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Immune system and angiogenesis-related potential surrogate biomarkers of response to everolimus-based treatment in hormone receptor-positive breast cancer: an exploratory study. [2021]

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

Phase I Study of Docetaxel and Temsirolimus in Refractory Solid Tumors. [2023]

15. England pubmed.ncbi.nlm.nih.gov

Combination of PI3K and MEK inhibitors yields durable remission in PDX models of PIK3CA-mutated metaplastic breast cancers. [2021]