What side effects are associated with this type of intervention?

Common treatments for Head and Neck Cancers, particularly those involving polyamine synthesis inhibition like DFMO and potentially AMXT 1501 dicaprate, often result in gastrointestinal disturbances (nausea, vomiting, diarrhea), hearing loss, and myelosuppression. Additionally, broader side effects of chemotherapy and targeted therapies for these cancers include mucositis, fatigue, neutropenia, and renal or hepatic toxicity.

What prior FDA approvals exist?

FDA-approved treatments for Head and Neck Cancers include a variety of chemotherapeutic agents, targeted therapies, and immunotherapies. Commonly used chemotherapeutic agents include cisplatin and carboplatin, which are platinum-based drugs. Targeted therapies such as cetuximab, an EGFR inhibitor, have also been approved. Immunotherapies like pembrolizumab and nivolumab, which are PD-1 inhibitors, have shown efficacy in treating recurrent or metastatic head and neck cancers. While specific drugs targeting polyamine synthesis like DFMO are not commonly highlighted in FDA approvals for head and neck cancers, the combination of such agents with other treatments is an area of ongoing research.

What other types of research exist?

Promising novel alternatives for Head and Neck Cancer patients in 2024 could include: 1) Targeted therapies such as EGFR inhibitors (e.g., cetuximab) or HER2 inhibitors (e.g., trastuzumab deruxtecan). 2) Immunotherapies like PD-1/PD-L1 inhibitors (e.g., pembrolizumab, nivolumab). 3) Novel enzyme inhibitors that target polyamine synthesis or related metabolic pathways. 4) Combination therapies that include new agents being tested in clinical trials for enhanced efficacy.

← Back to Search

Other

AMXT 1501 + DFMO for Cancer

Phase 1 & 2

Waitlist Available

Research Sponsored by Aminex Therapeutics, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patient is able to take oral medications and willing to use an at-home infusion pump

Active secondary malignancies will not be allowed

Must not have

Patients diagnosed with advanced solid tumors will not be eligible if they have a seizure disorder where >1 seizure has occurred within the last year

Patients with DIPG or DMG will not be eligible if they have seizure disorders that are not well-controlled

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects are not listed here for AMXT1501 + DFMO combination therapy; generally such treatments may cause fatigue, nausea, digestive issues potentially due to oral intake of drugs; skin reactions from infusions; as well as risks associated with compromised bone marrow function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I can take pills and am willing to use a pump for medicine at home.

Select...

I do not have any other active cancers.

Select...

I agree to use effective birth control during and for 3 months after the study.

Select...

I have been diagnosed with DIPG or DMG and meet specific study requirements.

Select...

I am 18 years old or older.

Select...

My cancer cannot be surgically removed, has spread, and standard treatments have failed or are not available.

Select...

I am 12 years or older and weigh more than 40 kg.

Select...

I am fully active or restricted in physically strenuous activity but can do light work.

Select...

I have been diagnosed with DIPG or DMG.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

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

Select...

My seizures are well-controlled, and I have DIPG or DMG.

Select...

I have an active liver condition.

Select...

I have a GI condition or had surgery that may affect drug absorption.

Select...

I am infected with HIV.

Select...

I take biotin or supplements with more than 30 µg of biotin daily.

Select...

I am not using any LHRH agonist/antagonist medications.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Determine DLTs and RP2Ds in AMXT 1501 in combination with IV DFMO

Determine safety and tolerability of AMXT1501 in combination with IV DFMO

Secondary study objectives

Characterize AMXT1501 and IV DFMO on the expression of immune related gene signatures

Characterize investigator defined Duration of Response (DOR)

Characterize investigator defined response Overall Response Rate (ORR) using RECIST v1.1

+2 more

Other study objectives

Palladium

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: ExpansionExperimental Treatment2 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: EscalationExperimental Treatment2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

AMXT1501

2018

Completed Phase 1

~60

DFMO

2014

Completed Phase 2

~240

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for head and neck cancers include surgery, radiation therapy, and chemotherapy. Chemotherapy often involves drugs like cisplatin, which forms DNA crosslinks and inhibits DNA synthesis, leading to cell death. Targeted therapies, such as cetuximab, inhibit the epidermal growth factor receptor (EGFR), blocking cell proliferation. Treatments like AMXT 1501 dicaprate and IV DFMO focus on inhibiting polyamine synthesis, which is crucial for cell growth and differentiation. DFMO inhibits ornithine decarboxylase, reducing polyamine levels, while AMXT 1501 dicaprate likely enhances this effect. This matters for head and neck cancer patients as targeting polyamine synthesis can potentially reduce tumor growth and improve treatment outcomes, offering a novel approach for those who may not respond well to traditional therapies.

Contradictory antitumor efficacies produced by the combination of DNA attacking drugs and polyamine antimetabolites.Antitumor-activity of orally-administered ammine amine platinum (iv) dicarboxylate complexes against a panel of human ovarian-carcinoma xenografts.Polyamine catabolism in colorectal cancer cells following treatment with oxaliplatin, 5-fluorouracil and N1, N11 diethylnorspermine.