Efficacy and safety of BMX-001 with radiation therapy for rectal cancer

A Randomized Phase 2 Trial of the Efficacy and Safety of Short and Long Course Radiation Therapy With and Without BMX-001 as Part of Total Neoadjuvant Therapy in Patients With Newly Diagnosed Locally Advanced Rectal Adenocarcinoma

This study is testing if adding a new treatment called BMX-001 to radiation therapy can help people with newly diagnosed rectal cancer feel better and stay safe during their treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 118 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Nebraska (Academic / other)
• Drugs / interventions: radiation
• Locations: 3 sites (Lexington, Kentucky and 2 other locations)
• Trial ID: NCT05254327 on ClinicalTrials.gov

What this trial studies

This Phase 2 trial evaluates the safety and efficacy of BMX-001 in combination with short-course radiotherapy (SCRT) or long-course chemoradiotherapy (LCCRT) for patients with newly diagnosed rectal adenocarcinoma. The study consists of two cohorts: a safety lead-in for patients receiving LCCRT and a randomized trial for those receiving SCRT. Patients will be assigned to receive either BMX-001 or no BMX-001 alongside their radiation therapy. The trial includes specific stopping rules based on safety and pharmacokinetic data to ensure patient safety throughout the study.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 or older with locally advanced rectal adenocarcinoma requiring total neoadjuvant therapy.

Not a fit: Patients with early-stage rectal cancer or those not requiring neoadjuvant therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could improve treatment outcomes for patients with rectal cancer by enhancing the efficacy of radiation therapy.

How similar studies have performed: Other studies have shown promise in combining novel agents with radiation therapy, but this specific combination is relatively novel.

Eligibility criteria

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
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 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 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.

   BMX-001 Specific Exclusion Criteria (Subjects meeting any of the following criteria are ineligible for study entry)
8. Inadequately controlled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \> 100 mmHg)
9. Active or history of postural hypotension and autonomic dysfunction within the past year
10. Known hypersensitivity to BMX-001
11. 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
12. 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
13. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent 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 a QTc interval \>450 milliseconds (ms) (CTCAE grade 1) using the specific/usual choice by clinical center for correction factor.
15. 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.

Where this trial is running

Lexington, Kentucky and 2 other locations

• Markey Cancer Center — Lexington, Kentucky, United States (Recruiting)
• University of Nebraska Medical Center — Omaha, Nebraska, United States (Recruiting)
• UT Health San Antonio MD Anderson Cancer Center — San Antonio, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Chi Lin, MD, PhD — University of Nebraska
• Study coordinator: Jessi E Delaney, RN, BSN

Conditions Rectal Cancer; Radiation