Trial of the Efficacy and Safety of Short and Long Course Radiation Therapy With/Without BMX-001

Inclusion Criteria:

1. Patients with pathologically confirmed locally advanced rectal adenocarcinoma whowill be receiving total neoadjuvant therapy regimen with curative intent.

2. AJCC stage II to III rectal adenocarcinoma that will require total neoadjuvanttherapy.

3. Adult, age > or equal to 18 years (for Nebraska, age of consent is ≥19 years old)

4. ECOG Performance Status 0-2

5. Hemoglobin ≥ 9.0 g/dl, ANC ≥ 1,500 /dl, platelets ≥ 100,000 /dl (The use oftransfusion 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 at the time of screening 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 prior to randomization.

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 ofcervical carcinoma in situ, basal cell or carcinoma of the skin, invasive cancerswith 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 corticosteroidsdose at the time of randomization. BMX-001 Specific Exclusion Criteria (Subjects meeting any of the following criteriaare ineligible for study entry)

8. Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHgand/or diastolic blood pressure > 100 mmHg)

9. Active or history of postural hypotension and autonomic dysfunction within the pastyear

10. Known hypersensitivity to BMX-001

11. Clinically significant (i.e. active) cardiovascular disease or cerebrovasculardisease, for example cerebrovascular accidents ≤ 6 months prior to study enrollment,myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, NewYork Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), orserious cardiac arrhythmia uncontrolled by medication or potentially interferingwith protocol treatment

12. History or evidence upon physical/neurological examination of central nervous systemdisease (e.g. seizures) unrelated to cancer unless adequately controlled bymedication or potentially interfering with protocol treatment

13. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair orrecent arterial thrombosis) within 6 months prior to start of study treatment

14. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of aQTc interval >450 milliseconds (ms) (CTCAE grade 1) using the specific/usual choiceby clinical center for correction factor.

15. A history of additional risk factors for Torsades de Pointes (TdP) (e.g., congestiveheart 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.