AMXT 1501 + DFMO for Cancer

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cancer treatment combining two drugs, AMXT 1501 and DFMO (also known as Eflornithine), to determine safe dosage levels and assess initial anti-cancer effects. The study targets individuals with advanced solid tumors that standard methods cannot treat or have resisted previous treatments. This includes specific cancers such as breast, ovarian, and lung cancers, among others. Eligible participants are those with these advanced cancers who have seen their current therapies fail and are willing to try a new treatment approach. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

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

Research has shown that the combination of AMXT 1501 and DFMO is safe and well-tolerated in patients with advanced cancer. Studies found that this treatment did not cause unexpected side effects, and patients managed it without serious issues. This suggests it could be a safe option for those considering participation in a clinical trial. However, as with any trial, there is always a chance of side effects, so discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AMXT1501 + DFMO because they represent a novel approach to cancer treatment. Unlike most current treatments that target cancer cells directly with chemotherapy or radiation, this combination aims to disrupt the cellular processes that cancer cells rely on for growth. AMXT1501 works by blocking specific transport mechanisms within the cancer cells, while DFMO inhibits a key enzyme necessary for cell division. This dual action could potentially lead to more effective treatment outcomes with fewer side effects compared to traditional therapies.

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

Research has shown that the combination of AMXT 1501 and DFMO affects polyamine metabolism, crucial for the growth and survival of neuroblastoma and other cancers. Animal studies demonstrated that this combination can significantly slow tumor growth. The FDA granted this combination "orphan drug" status, highlighting its potential to improve neuroblastoma treatment. In this trial, participants will join either the Escalation arm, involving dose escalation of DFMO with a fixed dose of AMXT 1501, or the Expansion arm, which will further characterize safety and early anti-tumor activity at the proposed RP2D level. Early trials focused on ensuring the safety and tolerability of this combination in patients with advanced cancer, laying the groundwork for further research into its effectiveness. ^{1 3 6 7 8}

Who Is on the Research Team?

Sue Lee, MD

Principal Investigator

Aminex Therapeutics, Inc.

Michael Armstrong, MD

Principal Investigator

IQVIA Biotech

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. esmoopen.com esmoopen.com/article/S2059-7029(25)01445-0/fulltext

Phase I dose-escalation trial of AMXT 1501 dicaprate plus ... The finding that polyamine depletion therapy is an effective therapeutic approach leading to significant tumor growth delay in animal models ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06465199

NCT06465199 | Eflornithine (DFMO) and AMXT 1501 for ... The purpose of this study is to evaluate the investigational oral drug AMXT 1501 in combination with oral eflornithine (DFMO). An investigational drug is ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2059702925014450

Phase I dose-escalation trial of AMXT 1501 dicaprate plus ... The primary objective of this study was to determine the safety and tolerability of oral AMXT 1501 in combination with DFMO in patients with advanced cancer.

4. targetedonc.com targetedonc.com/view/amxt-1501-and-dfmo-combination-achieve-fda-orphan-drug-designation

AMXT 1501 and DFMO Combination Achieve FDA Orphan ... FDA designates AMXT 1501 and DFMO as an orphan drug for neuroblastoma, aiming to enhance treatment outcomes for pediatric patients.

5. onclive.com onclive.com/view/amxt-1501-plus-difluoromethylornithine-nets-fda-orphan-drug-designation-in-neuroblastoma

AMXT 1501 Plus Difluoromethylornithine Nets FDA ... AMXT 1501, combined with DFMO, targets polyamine metabolism, crucial for neuroblastoma and other cancers' growth and resistance. · The FDA ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03536728

Oral AMXT 1501 Dicaprate in Combination With DFMO A Phase 1 study will be conducted to establish safety and dose level of AMXT 1501 dicaprate alone, and in combination with DFMO, in cancer patients. Detailed ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40913836/

Phase I dose-escalation trial of AMXT 1501 dicaprate plus ... Conclusions: Overall, AMXT 1501 in combination with DFMO was safe and tolerated with evidence of preliminary clinical activity. The RP2D was ...

8. aacrjournals.org aacrjournals.org/mct/article/22/12_Supplement/B132/730483/Abstract-B132-Addition-of-AMXT1501-polyamine

Abstract B132: Addition of AMXT1501 (polyamine uptake ... In contrast, addition of AMXT1501 plus DFMO to the backbone significantly extended survival (P< 0.001). Conclusions: We have increased the ...