AMB-05X for Colorectal Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Van K. Morris

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Tyrosine kinase inhibitors

Disqualifiers: Concurrent malignancy, Hepatobiliary disease, Autoimmune disorders, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

To investigate the efficacy of AMB-05X in patients with CRC with MRD as determined by a ctDNA(+) blood test and no clinically detectable radiographic disease.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on other systemic anti-cancer treatments or certain medications like pexidartinib or tyrosine kinase inhibitors within the past 4 weeks.

What safety data exists for AMB-05X (amonafide) in humans?

Amonafide, also known as AMB-05X, has been tested in humans for colorectal cancer. Common side effects included neutropenia (low white blood cell count), nausea, vomiting, fever, rash, and hair loss. Serious side effects were observed in some patients, such as severe neutropenia, sepsis (a severe infection), and anaphylaxis (a severe allergic reaction). ^{1 2 3 4 5}

Research Team

Van K. Morris

Principal Investigator

The University of Texas MD Anderson Cancer Center

Eligibility Criteria

This trial is for individuals with colorectal cancer who have had treatment intended to cure them but still show signs of microscopic residual disease through a positive ctDNA blood test, without any visible disease on scans.

Inclusion Criteria

I've completed all treatments for my stage I-IV colorectal cancer and currently show no signs of the disease.

My blood test for cancer DNA was positive 28 days after finishing all my planned treatments.

Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

I haven't taken specific medications in the last 4 weeks.

Patients with psychiatric illness/social situations that would limit compliance with study requirements

Exclusion of pregnant women and breastfeeding mothers

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AMB-05X for 6 months to determine ctDNA clearance rate

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Long-term follow-up

Participants are monitored for disease-free survival (DFS) and overall survival (OS) over 2 years

2 years

Treatment Details

Interventions

• AMB-05X (Virus Therapy)

Trial Overview The study tests the effectiveness of AMB-05X in preventing cancer recurrence in patients whose blood tests indicate remaining cancer traces at the molecular level after curative-intent treatments.

Participant Groups

Group I: AMB-05X Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

Findings from Research

Amonafide, administered at a dose of 300 mg/m2 for five consecutive days, showed no significant anti-tumor activity in 14 patients with recurrent or metastatic colorectal cancer, as there were no observed responses despite some patients having stable disease.

The treatment was associated with notable side effects, particularly neutropenia (Grade 3 or 4 toxicity in 5 out of 14 patients), along with other toxicities like nausea, vomiting, and fever, indicating a need for caution in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of amonafide (nafidamide, NSC 308847) in advanced colorectal cancer. O'Dwyer, PJ., Paul, AR., Hudes, GR., et al.[2020]

In a study of 124 colorectal cancer patients treated with the mFOLFOX6 regimen, the most common severe adverse events were neutropenia (40%) and leucopenia (16%), indicating that while the treatment can have significant side effects, it is generally tolerable.

The incidence of adverse events in this Japanese cohort was similar or lower than those reported in Western countries, suggesting that the mFOLFOX6 regimen is manageable in clinical practice and that informed consent forms were updated to better inform patients about potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Revision of the informed consent form for patients based on investigation of adverse events of mFOLFOX6 regimen]. Kato, T., Matsunaga, Y., Motokawa, S., et al.[2013]

In a trial involving 44 patients with advanced colorectal cancer, amonafide was administered at a dose of 300 mg/m2, but it resulted in no complete or partial responses, indicating an overall response rate of 0%.

The treatment caused significant toxicities, with 47% of patients experiencing grade 3 or higher adverse effects, including severe blood cell reductions and other serious conditions, suggesting that while the dose intensity was appropriate, the drug may not be effective for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of amonafide in advanced colorectal cancer: a SouthWest Oncology Group study. Brown, TD., Goodman, PJ., Fleming, T., et al.[2020]

Aflibercept, when combined with chemotherapy for metastatic colorectal cancer, is associated with a significantly increased risk of antiangiogenic adverse events, including hypertension (44.2% incidence) and proteinuria (31.3% incidence) among 2889 patients from 10 studies.

Compared to control treatments, aflibercept showed a notably higher incidence of severe adverse events, such as grade III/IV hypertension (OR: 7.20) and grade III/IV proteinuria (OR: 5.13), indicating that while it is effective, careful monitoring for these side effects is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis. Ge, P., Han, C., Reyila, A., et al.[2023]

References

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

Phase II study of amonafide (nafidamide, NSC 308847) in advanced colorectal cancer. [2020]

2. Japan pubmed.ncbi.nlm.nih.gov

[Revision of the informed consent form for patients based on investigation of adverse events of mFOLFOX6 regimen]. [2013]

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

Phase II trial of amonafide in advanced colorectal cancer: a SouthWest Oncology Group study. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. [2022]

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

Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis. [2023]