Safety Study of BMX-001 (Radio-protector) in Patients With Newly Diagnosed Anal Cancer

NCT03386500 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 0247-17-FB
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anal Cancer, Squamous Cell Carcinoma; Radiation Exposure

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose of BMX-001

  Maximum tolerated dose (MTD) of BMX-001 will be determined by the highest dose level at which at least 1 out of 6 participants experienced a Dose-Limiting Toxicity (DLT).

  Within first year of the study

• Count of Adverse Events, Serious Adverse Events and Dose Limiting Toxicities

  Acute grade 3 of normal tissue for adverse events (AE), serious adverse events (SAE) and dose limiting toxicities (DLT) will be recorded per Common Terminology Criteria for Adverse Events (CTCAE) 4.0.

  10 months post-radiation therapy

Secondary Outcomes (12)

• Impact of Study Treatment on Acute Rectal Bleeding

  10 months post-radiation therapy

• Impact of Study Treatment on Acute Rectal Pain

  10 months post-radiation therapy

• Impact of Study Treatment on Bowel Movements

  10 months post-radiation therapy

• Impact of Study Treatment on Acute Dysuria

  10 months post-radiation therapy

• Impact of Study Treatment on Acute Hematuria

  10 months post-radiation therapy

Other Outcomes (9)

• Effect of Study Treatment on Urine Levels of 4-hydroxynonenal

  4 months post-radiation therapy

• Effect of Study Treatment on Plasma Levels of 4-hydroxynonenal

  4 months post-radiation therapy

• Effect of Study Treatment on Serum Level of 8-OHdG

  4 months post-radiation therapy

Study Arms (1)

Concurrent Radiation Therapy, 5FU, Mitomycin and BMX-001

OTHER

One arm includes all enrolled patients.

Drug: BMX-001

Interventions

BMX-001 DRUG

BMX-001 at escalating doses in combination with standard RT, 33 fractions to 59.4 Gy, plus Mitomycin at the standard dosing of 10 mg/m2 administered IV bolus at day 1 and day 29 as well as 5FU 1g/m2/d day 1-4 and 29-32.

Also known as: MnTnBuOE-2-PyP5+, manganese butoxyethyl pyridyl porphyrin

Concurrent Radiation Therapy, 5FU, Mitomycin and BMX-001

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed locally advanced anal squamous cell carcinoma (including oligometastatic disease) with concurrent chemoradiation with standard Fluorouracil (5FU)/mitomycin regimen with curative intent
• Any cancer stage requiring a dose of 59.4 cGy
• years of age or older
• Karnofsky Performance Status (KPS) ≥ 60%
• Hemoglobin ≥ 9.0 g/dl (a transfusion or other intervention to achieve Hgb \> 9.0 g/dl is acceptable)
• Absolute neutrophil count (ANC) ≥ 1,500 /dl
• Platelets ≥ 100,000 /dl
• Serum creatinine ≤ 1.5 mg/dl, serum SGOT and bilirubin ≤ 1.5 times upper limit of normal
• Negative pregnancy test for women of child-bearing potential within 48 hours prior to first dose of BMX-001
• Use of a medically effective means of birth control until 12 months following the last study treatment for women of childbearing potential and male participants
• Positron Emission Tomography (PET)/ Computed Tomography (CT)/pelvic magnetic resonance imaging (MRI) done within 8 weeks of trial initiation

You may not qualify if:

• Breast-feeding
• Active infection requiring IV antibiotics within 7 days before enrollment
• Prior, unrelated malignancy requiring current active treatment, exception: cervical carcinoma in situ, basal cell or carcinoma of the skin, invasive cancers with a 5-year disease-free interval, resected cancer of the bladder, or low-grade prostate cancer (Gleason 6 or less)
• Prior history of Acantholytic squamous cell carcinoma (ASCC)
• Prior history of pelvic radiotherapy for any other type of malignancy
• Known hypersensitivity to Fluorouracil (5FU) and/or mitomycin
• Current corticosteroid use unless dose is stable or decreasing at study enrollment (anti-inflammatory properties could interrupt oxidative stress)
• Inadequately controlled hypertension (systolic blood pressure \>150 mmHg and/or diastolic blood pressure \> 100 mmHg)
• Active or history of postural hypotension and autonomic dysfunction within the past year
• Known hypersensitivity to BMX-001
• Clinically significant (active) cardiovascular disease or cerebrovascular disease, (e.g., cerebrovascular accidents ≤ 6 months prior to study enrollment, myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment
• History or evidence from physical/neurological examination of central nervous system disease (e.g. seizures) unrelated to cancer, potentially interfering with protocol treatment unless adequately controlled by medication
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis, including structural heart disease) within 6 months prior to start of study treatment
• Marked baseline prolongation of QT/QTc interval \[e.g., repeated demonstration of a QTc interval \>450 milliseconds (ms), CTCAE grade 1, using the specific/usual choice by clinical center for correction factor
• History of additional risk factors for Torsades de Pointes (TdP) (e.g., congestive heart failure, hypokalemia, known family history of Long QT Syndrome)

Sponsors & Collaborators

• BioMimetix JV, LLC: collaborator
• University of Nebraska: lead

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Related Publications (1)

• Myers MS, Kosmacek EA, Liew CS, Lushnikov AJ, Chatterjee A, Marky LA, Riethoven JM, Oberley-Deegan RE. BMX-001, a clinically relevant radioprotector, can reverse radiation-induced fibrosis when given three weeks after radiation, in part, by restoring methylation. Redox Biol. 2026 Mar;90:104020. doi: 10.1016/j.redox.2026.104020. Epub 2026 Jan 10.

  PMID: 41544350 DERIVED

MeSH Terms

Conditions

Anus Neoplasms

Interventions

Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin

Condition Hierarchy (Ancestors)

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases

Study Officials

• Chi Lin, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2017
• First Posted: December 29, 2017
• Study Start: November 28, 2017
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2029
• Last Updated: January 26, 2026

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)