BMX-001 for Anal Cancer

Overseen By Erin E Rogers, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Chi Lin, MD, PhD

Must be taking: 5FU, Mitomycin

Must not be taking: Corticosteroids

Disqualifiers: Breast-feeding, Active infection, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

24 Participants Needed

Trial Summary

What is the purpose of this trial?

Over 80% of anal cancers are squamous cell carcinoma (SCC). Current standard treatment for locally advanced squamous cell carcinoma of the anal canal is a combination of radiation therapy (RT) and concurrent chemotherapy. This allows for organ preservation in approximately 75% of patients. The use of concurrent radiation and chemotherapy with infusional 5-fluorouracil (5-FU) and mitomycin results in locoregional relapse rates of 20-32 and 5-year overall survival rates of 58-78%. However, while mitomycin significantly increases the rate of grade 4 toxicities, it improves local outcomes and has been considered a necessary agent in the care of anal cancer. Oxidative stress induced by radiotherapy and chemotherapy tends to protect tumor cells and promote normal tissue damage. A recently developed compound, BMX-001 (MnTnBuOE-2- PyP5+), is among the most highly potent metalloporphyrin compounds which reduce oxidative stress, thereby protecting normal tissues and augmenting tumor killing. In this Phase 1/2 study, the investigators will conduct a safety and efficacy study of the combination of BMX-001 with standard radiation therapy and concurrent (5FU)/mitomycin in newly diagnosed Anal Squamous Cell Carcinoma (ASCC) patients. The primary Phase 1 objective is to determine the maximum tolerated dose (MTD) of BMX-001 in ASCC patients receiving RT and concurrent 5FU/mitomycin chemotherapy. Three participants will be treated at Dose Level 1 and three at Dose Level 2, then three at Dose Level 3. Dose Limiting Toxicities (DLT) experienced by any participant will be used to determine the MTD. The Phase II objective is to examine the impact of BMX-001 on the overall acute ≥ grade 3 toxicity rate of the normal tissue including rectum, bladder, and skin in combination with RT and concurrent 5FU/mitomycin in treatment of newly diagnosed ASCC patients. These will be determined by participant reports, biological materials (blood, tissue, urine) sampling and imaging. Participant health-related quality of life will be assessed by two questionnaires.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on a stable or decreasing dose of corticosteroids (a type of medication that reduces inflammation) if you are taking them.

How does the drug BMX-001 differ from other treatments for anal cancer?

BMX-001 is unique because it is being studied specifically for anal cancer, a condition that lacks a consistent treatment approach due to its rarity. This drug may offer a novel option compared to existing treatments, which often involve aggressive therapies with significant side effects. ^{1 2 3 4 5}

Research Team

Chi Lin, MD

Principal Investigator

University of Nebraska

Eligibility Criteria

This trial is for adults over 19 with newly diagnosed anal squamous cell carcinoma who need chemoradiation. They must have a good performance status, normal organ function tests, and agree to use birth control. Excluded are those breastfeeding, with active infections or other cancers needing treatment, prior pelvic radiation, certain heart conditions, uncontrolled hypertension, known allergies to the drugs involved or BMX-001.

Inclusion Criteria

I have advanced anal cancer and will be treated with chemoradiation aimed at curing it.

My blood counts meet the required levels for hemoglobin, ANC, and platelets.

Serum creatinine ≤ 1.5 mg/dl, serum SGOT and bilirubin ≤ 1.5 times upper limit of normal

Exclusion Criteria

Breast-feeding

I have a history of anal squamous cell carcinoma.

My heart's electrical cycle is longer than normal.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive BMX-001 with concurrent radiation therapy and 5FU/mitomycin chemotherapy

8 weeks

Weekly visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 months

1 month, 4 months, and 10 months post-treatment visits

Pharmacokinetics

Blood samples are drawn to evaluate the pharmacokinetics of BMX-001

36 days

Day 1, Day 8, Day 22, and Day 36

Treatment Details

Interventions

• BMX-001

Trial Overview The study is testing the safety and effectiveness of BMX-001 as a radio-protector when combined with standard radiation therapy and chemotherapy (5FU/mitomycin) in treating anal cancer. Phase 1 will find the highest dose patients can take without severe side effects; Phase 2 will assess how well it reduces serious toxicity in tissues like rectum and skin.

Participant Groups

Group I: Concurrent Radiation Therapy, 5FU, Mitomycin and BMX-001 Experimental Treatment 1 Intervention

One arm includes all enrolled patients.

Who Is Running the Clinical Trial?

Chi Lin, MD, PhD

Lead Sponsor

Trials

3

Recruited

190+

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

BioMimetix JV, LLC

Industry Sponsor

Trials

11

Recruited

700+

Findings from Research

Anal neoplasms are rare and currently lack standardized diagnostic and treatment protocols due to insufficient data from clinical trials.

There is a potential opportunity to develop prospective Phase II clinical trials to establish uniform guidelines for the surgical treatment of these neoplasms, which could improve patient care and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uncommon anal neoplasms. Billingsley, KG., Stern, LE., Lowy, AM., et al.[2010]

HIV-infected individuals are at an increased risk for anal cancer and its precursor, anal HSIL, highlighting the need for effective screening and treatment strategies for these patients.

Current treatment options for anal cancer in HIV-positive patients show variability in outcomes, and there is a pressing need for prospective, controlled trials to improve treatment efficacy and reduce morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anal cancer and its precursors in HIV-positive patients: perspectives and management. Berry, JM., Palefsky, JM., Welton, ML.[2005]

In a study analyzing archival tissue from 48 patients with localized squamous cell carcinoma of the anus (SCCA), higher protein levels of immune checkpoint markers (like PD-1) and signaling proteins (like phospho-Akt) were found in patients who experienced cancer recurrence after chemoradiation.

The findings suggest that these biomarkers could help identify patients at higher risk for recurrence and support the development of immune-based therapies to enhance treatment outcomes beyond standard chemoradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer. Hernandez, S., Das, P., Holliday, EB., et al.[2023]

Anal cancer is highly prevalent among men who have sex with men (MSM) with HIV, largely due to the high rates of human papillomavirus (HPV) infection, making early detection crucial for improving outcomes.

The review suggests implementing a coordinated screening program led by trained nurses, focusing on HPV vaccination and regular anal cytology screenings, which could significantly enhance early diagnosis and prevention of anal cancer in this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of nurses in the prevention of anal cancer in HIV-infected men having sex with men - a focus on papillomavirus vaccination and anal cytology screening. Muñoz-Rodríguez, J., Millán-Revilla, L.[2023]

In a study of 50 patients with anal cancer, combined chemotherapy and radiation therapy resulted in a 7-year survival rate of 58%, with better outcomes for white patients and those with favorable performance status.

Of the 46 patients evaluated for treatment response, 34 achieved a complete response, indicating that this combined modality therapy is effective, with an 80% rate of freedom from locoregional progression at 7 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of combined modality therapy for patients with anal cancer (E7283). An Eastern Cooperative Oncology Group study. Martenson, JA., Lipsitz, SR., Lefkopoulou, M., et al.[2022]

References

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

Uncommon anal neoplasms. [2010]

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

Anal cancer and its precursors in HIV-positive patients: perspectives and management. [2005]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer. [2023]

4. Spain pubmed.ncbi.nlm.nih.gov

The role of nurses in the prevention of anal cancer in HIV-infected men having sex with men - a focus on papillomavirus vaccination and anal cytology screening. [2023]

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

Results of combined modality therapy for patients with anal cancer (E7283). An Eastern Cooperative Oncology Group study. [2022]