AMXT 1501 + DFMO for Cancer

Recruiting at 7 trial locations

Overseen By Project Manager

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Aminex Therapeutics, Inc.

Must not be taking: Corticosteroids, Anticonvulsants, Biotin, others

Disqualifiers: Seizure disorder, Cardiovascular disease, Active infections, others

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

Compensation: Varies

Number of Visits: Unknown

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the safety of a pill called AMXT1501 combined with an IV drug in patients with advanced cancers. It aims to find out if this combination can safely help fight cancer by affecting cancer cells and blood cells. The IV drug has been studied with other drugs, showing potential in enhancing the effectiveness of chemotherapy in various animal cancer models.

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, certain medications like enzyme-inducing anticonvulsants and high doses of biotin are not allowed. It's best to discuss your specific medications with the trial team.

What makes the drug AMXT 1501 + DFMO unique for cancer treatment?

The drug combination of AMXT 1501 and DFMO is unique because DFMO is an irreversible inhibitor of an enzyme involved in cell growth, and it has shown potential in stopping cancer cell growth when used alone or with other drugs. This combination may offer a novel approach by targeting specific pathways in cancer cells that are not addressed by standard treatments. ^{1 2 3 4 5}

Research Team

Sue Lee, MD

Principal Investigator

Aminex Therapeutics, Inc.

Michael Armstrong, MD

Principal Investigator

IQVIA Biotech

Eligibility Criteria

This trial is for patients aged 12 and older, weighing over 40 kg, with various advanced solid tumors where standard treatments have failed or are not available. Participants must be able to take oral medication, use an at-home infusion pump, provide a CSF sample and tumor tissue biopsy, and agree to contraception use. Exclusions include recent cancer treatment within the last 4-6 weeks, uncontrolled seizures in DIPG/DMG patients, significant cardiovascular disease within the past 6 months, active liver disease or infections like HIV.

Inclusion Criteria

My guardians have consented to my participation in the study, and I agree to follow the study's procedures.

I do not have any other active cancers.

I have recovered from side effects of my previous cancer treatments.

Exclusion Criteria

You have had allergic reactions to a similar type of medicine before.

I haven't had cancer treatment like radiation, surgery, or chemo in the last 4 weeks.

I have not had more than one seizure in the past year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation of DFMO with AMXT1501 fixed dose following a 3 + 3 dose escalation design to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D)

28 days per cycle

Continuous infusion

Expansion

Expansion cohort to further characterize safety at proposed RP2D dose level with repeat dosing and characterize early anti-tumor activity

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• AMXT1501
• DFMO

Trial Overview The study tests AMXT 1501 dicaprate combined with IV DFMO on safety and optimal dosing levels in cancer patients. It's a Phase 1B/2A trial focusing on those with unresectable or metastatic solid tumors including ovarian cancer and gliomas among others.

Participant Groups

Group I: Expansion Experimental Treatment 2 Interventions

The expansion cohort will include up to 40 evaluable patients at a proposed RP2D level of AMXT1501 and DFMO defined by AMXT1501-101A study to further characterize safety at proposed RP2D dose level with repeat dosing, and characterize early anti-tumor activity.

Group II: Escalation Experimental Treatment 2 Interventions

Dose escalation of DFMO with AMXT1501 fixed dose will follow a 3 + 3 dose escalation design. The AMXT 1501 starting dose administered in the first cohort will be 1200mg total daily dose (200 mg capsules; 3 capsules in morning; 3 capsules in evening) along with IV DFMO administered in continuous infusion at 2mL/hr over a 28 days per cycle. The patient can be treated for additional 28 day treatment cycles as deemed appropriate by their study investigator. Dose escalation of DFMO alone will increase per cohort.

Who Is Running the Clinical Trial?

Aminex Therapeutics, Inc.

Lead Sponsor

Trials

4

Recruited

320+

Findings from Research

Difluoromethylornithine (DFMO) works as an irreversible inhibitor of the enzyme ornithine decarboxylase, which is crucial for polyamine synthesis, thereby affecting cell survival and showing potential as an anticancer agent.

DFMO has demonstrated cytostatic activity and effectiveness both as a standalone treatment and in combination with other chemotherapy drugs for certain cancers and leukemias, highlighting its role in cancer treatment and prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Difluoromethylornithine in cancer: new advances. Alexiou, GA., Lianos, GD., Ragos, V., et al.[2022]

In a study involving 38 patients with various cancers, DFMO was added to conventional chemotherapy and showed negligible gastrointestinal, hematologic, and biochemical toxicity, with the main side effect being ototoxicity in 15.8% of patients.

Despite its safety profile, DFMO did not demonstrate any significant improvement in disease progression compared to conventional chemotherapy alone, indicating that it may not enhance the efficacy of standard cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I-II clinical trial with alpha-difluoromethylornithine--an inhibitor of polyamine biosynthesis. Horn, Y., Schechter, PJ., Marton, LJ.[2019]

alpha-Difluoromethylornithine (DFMO) effectively inhibits the growth of Burkitt's lymphoma cells, showing significant reductions in cell proliferation and colony formation at concentrations of 50 micrograms/ml or higher.

When combined with doxorubicin or cisplatin, DFMO enhances the effectiveness of these chemotherapy agents, demonstrating synergistic effects that could improve treatment outcomes for lymphoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of alpha-difluoromethylornithine alone and in combination with doxorubicin hydrochloride, cis-diamminedichloroplatinum (II), and vinblastine sulfate on the growth of P3J cells in vitro. Allen, ED., Natale, RB.[2013]

References

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

In vitro response of a human colon tumor xenograft and a lung adenocarcinoma cell line to alpha-difluoromethylornithine alone and in combination with 5-fluorouracil and doxorubicin. [2019]

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

Difluoromethylornithine in cancer: new advances. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Phase I-II clinical trial with alpha-difluoromethylornithine--an inhibitor of polyamine biosynthesis. [2019]

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

A phase II breast cancer chemoprevention trial of oral alpha-difluoromethylornithine: breast tissue, imaging, and serum and urine biomarkers. [2018]

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

Effect of alpha-difluoromethylornithine alone and in combination with doxorubicin hydrochloride, cis-diamminedichloroplatinum (II), and vinblastine sulfate on the growth of P3J cells in vitro. [2013]