Standard Chemotherapy and Short or Long Course Radiation Therapy with or without BMX-001 for the Treatment of Stage II-III Rectal Cancer
This phase II trial tests whether BMX-001 in addition to standard chemotherapy regimens and long or short course radiation therapy works to protect healthy tissue in patients with stage II-III rectal adenocarcinoma that has spread to nearby tissue or lymph nodes (locally advanced). Chemotherapy drugs, such as oxaliplatin, leucovorin, fluorouracil, and capecitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy, like short course radiotherapy (SCRT) and long course chemoradiotherapy (LCCRT) uses high energy rays to kill cancer cells and shrink tumors. BMX-001 is a drug that protects healthy tissues by destroying harmful substances resulting from radiation therapy. Giving BMX-001 in addition of chemotherapy and radiation therapy may protect more healthy tissue in patients with rectal cancer.
Inclusion Criteria
- Patients with pathologically confirmed locally advanced rectal adenocarcinoma who will be receiving total neoadjuvant therapy regimen with curative intent
- American Joint Committee on Cancer (AJCC) stage II to III rectal adenocarcinoma that will require total neoadjuvant therapy
- Adult, age >= 18 years (for Nebraska, age of consent is >= 19 years old)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 or Karnofsky performance status (KPS) >= 60%
- Hemoglobin >= 9.0 g/dl (the use of transfusion or other intervention to achieve hemoglobin [Hgb] > 9.0 g/dl is acceptable)
- Absolute neutrophil count (ANC) >= 1,500 /ul
- Platelets >= 100,000 /ul
- Serum glutamic-oxaloacetic transaminase (SGOT) =< 1.5 times upper limit of normal
- Bilirubin =< 1.5 times upper limit of normal
- Serum creatinine < 1.5 mg/dl within 2 weeks prior to enrollment or creatinine clearance (CC) >= 50 ml/min within 2 weeks prior to enrollment determined by 24-hour collection or estimated by Cockcroft-Gault formula
- 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 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
- Chest/abdominal/pelvic (CAP) CT/ pelvic MRI done within 8 weeks prior to randomization
Exclusion Criteria
- Breast-feeding or pregnant
- Active infection requiring 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 rectal adenocarcinoma (RAC)
- Prior history of pelvic radiotherapy for any other type of malignancy
- Known hypersensitivity or contraindication to any agent in FOLFOX or CAPOX regimen
- 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 the study
- Patients on oral coumarin-derivative anticoagulant therapy will not be allowed to receive capecitabine concurrently unless they have their anticoagulant response (international normalized ratio [INR] or prothrombin time) monitored frequently in order to adjust the anticoagulant dose accordingly
- 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 > 450 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)
Additional locations may be listed on ClinicalTrials.gov for NCT05254327.
Locations matching your search criteria
United States
Kentucky
Lexington
Nebraska
Omaha
Texas
San Antonio
PRIMARY OBJECTIVE:
I. To examine the efficacy of MnSOD mimetic BMX-001 (BMX-001) as a normal tissue radioprotector on reduction of acute toxicity of SCRT or LCCRT (capecitabine concurrent with RT) as part of total neoadjuvant therapy (TNT) (TNT = SCRT or LCCRT followed chemotherapy with fluorouracil/leucovorin calcium/oxaliplatin [FOLFOX] or capecitabine/oxaliplatin [CAPOX].
SECONDARY OBJECTIVES:
I. To characterize the pharmacokinetic (PK) profile of BMX-001 in combination with fluorouracil (5-FU)/capecitabine in subjects with newly diagnosed locally advanced rectal adenocarcinoma.
II. To examine the impact of BMX-001 with TNT on 30 days postoperative complications.
III. To examine the efficacy of BMX-001 with TNT on reduction of chronic toxicity of SCRT or LCCRT.
IV. To assess the impact of BMX-001 with TNT on local control, overall survival (OS) and disease-free survival (DFS).
V. To describe patient-reported outcomes of health-related quality of life (HRQoL) in rectal adenocarcinoma (RAC) patients treated with BMX-001 in combination with TNT.
EXPLORATORY OBJECTIVES:
I. To assess the impact of BMX-001 with TNT on tumor pathologic response and on normal rectal tissue.
II. To measure blood and urine for markers of chemoradiation damage through a variety of measurements before and after radiation therapy, before and after chemotherapy, and before and after surgery.
III. To determine the effect of BMX-001 with chemoradiation on tumor burden via circulating tumor deoxyribonucleic acid (ctDNA) measurement, before and after radiation therapy, before and after chemotherapy, and before and after surgery.
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT 2 (SCRT): Patients are randomized to 1 of 2 arms.
ARM A: Patients undergo SCRT daily (QD) for 5 days. Patients receive BMX-001 subcutaneously (SC) once, 4 days before SCRT, then twice during SCRT, with an additional dose when SCRT concludes. Patients then receive FOLFOX regimen (oxaliplatin and leucovorin intravenously [IV] over 2 hours, fluorouracil IV bolus and fluorouracil IV infusion over 46 hours on day 1) or CAPOX regimen (oxaliplatin IV over 2 hours on day 1 and capecitabine orally [PO] twice daily [BID] on days 1 to 14). Treatment with FOLFOX repeats every 14 days for 9 cycles, and treatment with CAPOX repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo surgery.
ARM B: Patients undergo SCRT QD for 5 days. Patients then receive FOLFOX regimen or CAPOX regimen. Treatment with FOLFOX repeats every 14 days for 9 cycles, and treatment with CAPOX repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo surgery.
COHORT 1 (LCCRT): Patients are randomized to 1 of 2 arms.
ARM C: Patients undergo LCCRT QD and receive fluorouracil IV QD over 24 hours or capecitabine PO BID 5 days a week for 6 weeks. Patients receive BMX-001 SC twice weekly BIW during LCCRT with 2 additional doses after completion of LCCRT. Patients then receive FOLFOX or CAPOX regimen. Treatment with FOLFOX repeats every 14 days for 8 cycles, and treatment with CAPOX repeats every 21 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo surgery.
ARM D: Patients undergo LCCRT QD and receive fluorouracil IV QD over 24 hours or capecitabine PO BID 5 days a week for 6 weeks. Patients then receive FOLFOX or CAPOX regimen. Treatment with FOLFOX repeats every 14 days for 8 cycles, and treatment with CAPOX repeats every 21 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo surgery.
All patients undergo computed tomography (CT) throughout the trial and colonoscopy or sigmoidoscopy during screening. Patients also undergo magnetic resonance imaging (MRI) during screening and on the trial. Additionally, patients undergo blood sample collection on the trial and during follow up as well as urine sample collection on the trial. Patients may also undergo colonoscopy or sigmoidoscopy during follow up.
After completion of study treatment, patients are followed up at 1 month, 4 months, and 10 months and then every 6 months for up to 5 years
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationUniversity of Nebraska Medical Center
Principal InvestigatorChi Lin
- Primary ID012-22
- Secondary IDsNCI-2022-03371
- ClinicalTrials.gov IDNCT05254327