MnSOD Mimetic BMX-001 in Treating Patients with Anal Cancer Undergoing Radiation Therapy and Chemotherapy
- Patients with pathologically confirmed locally advanced anal squamous cell carcinoma (including oligometastatic disease) who will be receiving concurrent chemoradiation with standard 5FU/mitomycin regimen with curative intent
- Any cancer stage that will require a dose of 59.4 centigray (cGy)
- Karnofsky performance status (KPS) >= 60%
- Hemoglobin (Hgb) >= 9.0 g/dl; (the use of 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 glutamic-oxaloacetic transaminase (SGOT) =< 1.5 times upper limit of normal
- Bilirubin =< 1.5 times upper limit of normal
- Signed, written informed consent
- Negative pregnancy test for women of child-bearing potential within 48 hours prior to first dose of BMX-001
- Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study and until 12 months following the last study treatment
- Positron emission tomography/ computed tomography (PET/CT)/ pelvic magnetic resonance imaging (MRI) done within 8 weeks of trial initiation
- Active infection requiring intravenous (IV) antibiotics 7 days before enrollment
- Prior, unrelated malignancy requiring current active treatment with the exception of 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 (Gleason 6 or less) prostate cancer
- Prior history of ASCC
- Prior history of pelvic radiotherapy for any other type of malignancy
- Known hypersensitivity to 5FU and/or mitomycin
- Because corticosteroids are anti-inflammatory and could interrupt oxidative stress, patients will be required to be on stable or decreasing corticosteroids dose at the time of the study
- BMX-001 SPECIFIC EXCLUSION CRITERIA:
- Inadequately controlled hypertension (defined as 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 (i.e. active) cardiovascular disease or cerebrovascular disease, for example 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 upon physical/neurological examination of central nervous system disease (e.g. seizures) unrelated to cancer unless adequately controlled by medication or potentially interfering with protocol treatment
- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to start of study treatment
- A marked baseline prolongation of QT/corrected QT (QTc) interval (e.g., repeated demonstration of a QTc interval > 480 milliseconds (ms) (Common Terminology Criteria for Adverse Events [CTCAE] grade 1) using the specific/usual choice by clinical center for correction factor
- A history of additional risk factors for Torsades de Pointes (TdP) (e.g., congestive heart failure, hypokalemia, known family history of long QT syndrome)
I. To determine the maximum tolerated dose (MTD) of MnSOD mimetic BMX-001 (BMX-001) in anal squamous cell carcinoma (ASCC) patients receiving radiation therapy (RT) and concurrent fluorouracil (5FU)/mitomycin chemotherapy. (Phase I)
II. 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. (Phase II)
I. To examine the impact on acute gastrointestinal (GI) symptoms including rectal bleeding and pain, frequency and texture of bowel movement of BMX-001 in combination with RT and concurrent 5FU/mitomycin in treatment of newly diagnosed ASCC patients.
II. To examine the impact on acute genitourinary (GU) symptoms including dysuria, hematuria and urinary frequency of BMX-001 in combination with RT and concurrent 5FU/mitomycin in treatment of newly diagnosed ASCC patients.
III. To examine the impact on acute perianal dermatitis of BMX-001 in combination with RT and concurrent 5FU/mitomycin in ASCC patients.
IV. To examine the impact on chronic proctitis including rectal bleeding and fibrosis of BMX-001 in combination with RT and concurrent 5FU/mitomycin in ASCC patients.
V. To assess the effect of BMX-001 in combination with RT and concurrent 5FU/mitomycin in newly diagnosed ASCC patients on local control, overall survival (OS), locoregional progression free survival (PFS).
I. To describe patient-reported outcomes of health-related quality of life (HRQoL) in ASCC patients treated with BMX-001 in combination with RT and concurrent 5FU/mitomycin.
II. To characterize plasma levels of oxidative stress biomarkers during BMX-001 in combination with RT and concurrent 5FU/mitomycin.
III. To characterize the single-dose and repeated-dose pharmacokinetic profiles of BMX-001 when delivered in combination RT and concurrent 5FU/mitomycin.
IV. To assess the impact of BMX-001 on fibrosis, bleeding or vascular changes.
OUTLINE: This is a dose-escalation study.
Patients receive MnSOD mimetic BMX-001 subcutaneously (SC) once before the start of radiation therapy, and then twice weekly for 6-7 weeks. Patients also undergo standard of care radiation therapy daily for 5-7 weeks and receive fluorouracil intravenously (IV) continuously and mitomycin IV on days 1 and 29.
After completion of study, patients are followed up at 1, 4 and 10 months and then periodically thereafter.
Trial Phase Phase I/II
Trial Type Treatment
University of Nebraska Medical Center
- Primary ID 247-17
- Secondary IDs NCI-2017-02375, BMX-ASCC-001
- Clinicaltrials.gov ID NCT03386500