Overview

In this Phase 2 study, we will conduct an efficacy and safety study of the combination of investigational drug BMX-001, with short-course radiotherapy (SCRT) or long-course chemoradiotherapy (LCCRT) as part of total neoadjuvant therapy in newly diagnosed rectal adenocarcinoma (RAC) patients.

Eligibility

Inclusion Criteria:

1. Patients with pathologically confirmed locally advanced rectal adenocarcinoma who will be receiving total neoadjuvant therapy regimen with curative intent.
2. AJCC stage II to III rectal adenocarcinoma that will require total neoadjuvant therapy.
3. Adult, age > or equal to 18 years (for Nebraska, age of consent is ≥19 years old)
4. ECOG Performance Status 0-2 or Karnofsky Performance Status (KPS) ≥ 60%
5. Hemoglobin ≥ 9.0 g/dl, ANC ≥ 1,500 /dl, platelets ≥ 100,000 /dl (The use of transfusion or other intervention to achieve Hgb > 9.0 g/dl is acceptable)
6. Serum SGOT and bilirubin ≤ 1.5 times upper limit of normal
7. Adequate renal function defined as follows:

        1)Serum creatinine < 1.5 mg/dl within 2 weeks prior to enrollment or 2)Creatinine clearance
        (CC) ≥ 50 ml/min within 2 weeks prior to enrollment determined by 24-hour collection or
        estimated by Cockcroft-Gault formula: CCr male = [(140 - age) x (wt in kg)]/[(Serum Cr
        mg/dl) x (72)], CCr female = 0.85 x (CrCl male) 8. Signed, written informed consent prior
        to completing any study specific procedures 9. Negative pregnancy test for women of
        child-bearing potential within 48 hours prior to first dose of BMX-001 10. Women of
        childbearing potential and male participants must agree to use two forms of 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 11. Chest/Abdominal/Pelvic
        (CAP) CT/ pelvic MRI done within 8 weeks of trial initiation
        Exclusion Criteria:
          1. Breast-feeding or pregnant
          2. Active infection requiring IV antibiotics 7 days before enrollment
          3. 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
          4. Prior history of rectal adenocarcinoma (RAC)
          5. Prior history of pelvic radiotherapy for any other type of malignancy
          6. Known hypersensitivity or contraindication to any agent in FOLFOX or CAPOX regimen.
          7. Because corticosteroids are anti-inflammatory and could interrupt oxidative stress,
             patients will be excluded unless they are on stable or decreasing corticosteroids dose
             at the time of randomization.
          8. Patients on oral coumarin-derivative anticoagulant therapy will not be allowed to
             receive capecitabine concurrently unless they have their anticoagulant response (INR
             or prothrombin time) monitored frequently in order to adjust the anticoagulant dose
             accordingly.
             BMX-001 Specific Exclusion Criteria (Subjects meeting any of the following criteria
             are ineligible for study entry)
          9. Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg
             and/or diastolic blood pressure > 100 mmHg)
         10. Active or history of postural hypotension and autonomic dysfunction within the past
             year
         11. Known hypersensitivity to BMX-001
         12. 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
         13. 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
         14. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
             recent arterial thrombosis) within 6 months prior to start of study treatment
         15. A 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.
         16. A history of additional risk factors for Torsades de Pointes (TdP) (e.g., congestive
             heart failure, hypokalemia, known family history of Long QT Syndrome).
        Note: Inclusion of Women and Minorities Both men and women and members of all races and
        ethnic groups are eligible for this trial.