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

Prior treatment

• 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
• Current corticosteroid use unless dose is stable or decreasing at study enrollment (anti-inflammatory properties could interrupt oxidative stress)
• 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
• 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

Other illness

• Known hypersensitivity to Fluorouracil (5FU) and/or mitomycin
• 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
• 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

Lab values

• 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

Other

• Breast-feeding

• 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