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

A Phase 1/2 Trial for Patients With Newly Diagnosed Anal Cancer Treated With Concurrent Radiation Therapy, 5FU, Mitomycin and BMX-001

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Radiation Exposure; Anal Cancer, Squamous Cell Carcinoma
• Intervention / Treatment: Drug: BMX-001

Detailed Description

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 (RT) and concurrent 5-fluorouracil (5FU)/mitomycin in newly diagnosed anal squamous cell carcinoma (ASCC) participant. A recently completed Phase 1 study using BMX-001 with concurrent chemotherapy and radiation therapy in patient with newly diagnosed high-grade gliomas (BMX-HGG-001) demonstrated no adverse effects in subcutaneous dosing up to 28 mg/subject load with half the loading dose (14 mg/subject) given biweekly for 8 weeks in 12 participants. One of three participants dosed with 42 mg/subject load with half the loading dose given biweekly for 8 weeks experienced dose-limiting toxicity (DLT) of grade 3 tachycardia and grade 3 hypotension at loading dose. These resolved with treatment within 24 hours and the participant returned to the study with no recurrence for the maintenance does. The sponsor determined that the Recommended Phase 2 Dose (RP2D) of BMX-001 is 28 mg/subject load followed by 14 mg/subject twice a week for up to eight weeks as the maximum dose that was tolerated with no adverse effects. The most common related toxicity seen in this study grade 1 injection site reaction. There is no apparent toxicity to end organ tissues or bone marrow.

For this study, after completion of Phase 1 and establishment of a RP2D for the treatment regimen in participants undergoing radiation therapy and chemotherapy, the protocol will proceed to Dose Level 3, after completion of Dose Level 1 and Dose Level 2. Up to 20 participants will be enrolled with a safety lead-in of 6 participants to confirm safety in subjects in this cohort receiving radiation therapy and 5FU/mitomycin. To evaluate the pharmacokinetics (PK) of BMX-001 in combination with current chemoradiation, blood samples will be drawn for analysis in three to six participants in enrolled in the safety lead-in. Next, the first dose of BMX-001 will be administered subcutaneously from 4 days up to 1 hour prior to the start of radiation treatment. Blood will be drawn for PK on the following days: Day 1 (before and after loading dose), Day 8, Day 22 and Day 36. Measures will be obtained at approximately the following times: -1 to 0 hour (before loading dose), 30 minutes after the drug is given, 4 hours post-dose, and 24 hours post-dose. Samples will be analyzed for BMX-001 using validated analytical methods. Skin, gastrointestinal (GI), and genitourinary (GU) symptoms will be measured on the day of screening, weekly during RT, 1 months, 4 months and 10 months after the completion of RT. Perianal skin will be assessed weekly during RT, 1 month, 4 months, and 10 months after completion of RT. Further follow up will be per standard of care.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• 19 years of age or older
• ECOG Performance Status (ECOG) ≥ 2
• 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

Exclusion Criteria:

• 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)
• Documented recent electrolyte disturbances (hypokalemia, hypomagnesemia, or hypocalcemia) that were clinically significant and not corrected. No additional laboratory testing is required solely for screening.
• Medical necessity for anti-arrhythmics with significant risk of QTc prolongation such as class I and class III anti-arrhythmics. These include but are not limited to amiodarone, quinidine, dofetilide, sotalol, flecainide, and lidocaine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Concurrent Radiation Therapy, 5FU, Mitomycin and BMX-001; One arm includes all enrolled patients.	Drug: BMX-001; 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.; Other Names: manganese butoxyethyl pyridyl porphyrin; MnTnBuOE-2-PyP5+

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of Study Treatment on Acute Rectal Bleeding	Acute grade 3 of normal tissue for rectal bleeding will be recorded per Common Terminology Criteria for Adverse Events (CTCAE) 4.0.	10 months post-radiation therapy
Impact of Study Treatment on Acute Rectal Pain	Acute grade 3 of normal tissue for rectal pain will be recorded per Common Terminology Criteria for Adverse Events (CTCAE) 4.0.	10 months post-radiation therapy
Impact of Study Treatment on Bowel Movements	Acute grade 3 of normal tissue for diarrhea will be recorded per Common Terminology Criteria for Adverse Events (CTCAE) 4.0.	10 months post-radiation therapy
Impact of Study Treatment on Acute Dysuria	Acute grade 3 of normal tissue for dysuria will be recorded per Common Terminology Criteria for Adverse Events (CTCAE) 4.0.	10 months post-radiation therapy
Impact of Study Treatment on Acute Hematuria	Acute grade 3 of normal tissue for hematuria will be recorded per Common Terminology Criteria for Adverse Events (CTCAE) 4.0.	10 months post-radiation therapy
Impact of Study Treatment on Acute Urinary Frequency	Acute grade 3 of normal tissue for urinary frequency will be recorded per Common Terminology Criteria for Adverse Events (CTCAE) 4.0.	10 months post-radiation therapy
Impact of Study Treatment on Acute Perianal Grade 3 Radiation Dermatitis	Acute grade 3 of normal tissue for acute perianal grade 3 radiation dermatitis will be recorded per Common Terminology Criteria for Adverse Events (CTCAE) 4.0.	10 months post-radiation therapy
Impact of Study Treatment on Late Rectal Bleeding	Acute grade 3 of normal tissue for late rectal bleeding per will be recorded per Common Terminology Criteria for Adverse Events (CTCAE) 4.0.	10 months post-radiation therapy
Impact of Study Treatment on Rectal Fibrosis	Acute grade 3 of normal tissue for rectal fibrosis will be evaluated by endoscopy.	10 months post-radiation therapy
Effect of Study Treatment on Overall Survival	Overall survival (OS) rate will be determined.	10 months post-radiation therapy
Effect of Study Treatment on Locoreginal Progression-free Survival	Locoreginal progression-free survival rate survival (PFS) will determined.	10 months post-radiation therapy
Effect of Study Treatment on Local Control	The local recurrence rate will be assessed.	10 months post-radiation therapy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Study Treatment on Urine Levels of 4-hydroxynonenal	4-hydroxynonenal (4-HNE) will be measured in urine.	4 months post-radiation therapy
Effect of Study Treatment on Plasma Levels of 4-hydroxynonenal	4-hydroxynonenal (4-HNE) will be measured in plasma.	4 months post-radiation therapy
Effect of Study Treatment on Serum Level of 8-OHdG	8-OHdG will be measured in serum.	4 months post-radiation therapy
Effect of Study Treatment on Blood Cells Level of 8-OHdG	8-OHdG will be measure in blood cells.	4 months post-radiation therapy
Effect of Study Treatment on Urine Level of 8-OHdG	8-OHdG will be measured in urine.	4 months post-radiation therapy
Effect of Study Treatment on Urine Levels of Malondialdehyde	Malondialdehyde (MDA) will be measured in urine.	4 months post-radiation therapy
Effect of Study Treatment on Plasma Levels of Malondialdehyde	Malondialdehyde (MDA) will be measured in plasma.	4 months post-radiation therapy
Single-dose and Repeated-dose Pharmacokinetic Profiles of BMX-001	Serum drug concentration of BMX-001 will be measured after single-dose and repeated-dose BMX-001 delivery.	Up to 36 days of the chemoradiation phase
Effect of Study Treatment on Participant-reported Outcomes of Health-related Quality of Life	Participant-reported outcomes will be evaluated with the EORTC QLQ-CR29 questionnaire. This instrument consists of five functional scales, four subscales and 19 single items related to various colorectal cancer-related symptoms and functional problems. Scores can be linearly transformed to a range from 0 to 100, where higher scores generally indicate better functioning or a higher level of symptoms.	10 months post-radiation therapy

Collaborators and Investigators

• Sponsor: University of Nebraska
• Collaborators: BioMimetix JV, LLC
• Investigators: Principal Investigator: Chi Lin, MD, University of Nebraska

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2017
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: December 7, 2017
• First Submitted That Met QC Criteria: December 20, 2017
• First Posted (Actual): December 29, 2017

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Anus Diseases; Rectal Neoplasms; Anus Neoplasms; Physiological Effects of Drugs; Trace Elements; Micronutrients; Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin
• Other Study ID Numbers: 0247-17-FB; BMX-ASCC-001 (Other Identifier: Biomimetix)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No