Total Neoadjuvant Therapy With mFOLFOX and Short-course Radiation in Resectable Rectal Cancer

This is an interventional treatment trial for Rectal Cancer focused on measuring Resectable, Rectal Read More

Inclusion Criteria:

• Pathologic diagnosis of adenocarcinoma of the rectum (diagnosis by tissue biopsy) within 90 days prior to registration. At least a portion of the tumor must be located below the peritoneal reflection or begin within 12 cm of the anal verge on flexible endoscopy

• Clinically staged (AJCC 8th ed.) T3-4 N0 M0 or T any N1-2 M0 based upon the following minimum diagnostic workup:

  • Colonoscopy within 90 days prior to registration
  • Within 28 days prior to registration:
• History/physical examination
• Imaging to exclude distant metastases: either contrast-enhanced CT of the chest, abdomen, and pelvis or whole-body PET-CT
• Pelvic MRI (preferred) or transrectal ultrasound (TRUS) for T staging
• ECOG Performance Status ≤1
• Age ≥ 18 years

• Adequate bone marrow function defined as follows:

  • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
  • Platelets ≥ 100,000 cells/mm3
  • Hemoglobin ≥ 8.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb ≥8.0 g/dL is acceptable.)

• Adequate liver and renal function defined as follows:

  • AST and alkaline phosphatase < 2.5 x upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 ULN
  • Calculated creatinine clearance (CrCl) > 50 mL/min using Cockcroft-Gault formula as calculated by the standard Cockcroft-Gault equation using age, actual weight, creatinine, and gender
• Must be deemed a candidate for curative resection by the surgical oncologist who will be performing the operation
• Women of childbearing potential (WCBP) must have a negative serum pregnancy test performed within 7 days prior to the start of chemotherapy.
• WCBP and men must agree to use a medically accepted form of birth control during the treatment and for 3 months following completion of chemotherapy.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Prior RT that would result in overlap of RT fields with the planned study treatment
• Clinically significant cardiac disease, including major cardiac dysfunction, such as uncontrolled angina, clinical congestive heart failure with New York Heart Association (NYHA) class III or IV, ventricular arrhythmias requiring anti-arrhythmic therapy, recent (within the last 6 months) myocardial infarction, or unstable disease
• Serious (ie, ≥ grade 3) uncontrolled infection

• Within 30 days prior to registration, either of the following that would, in the opinion of the investigator, preclude study therapy:

  • Chronic obstructive pulmonary disease exacerbation
  • Respiratory illness requiring hospitalization
• Hepatic insufficiency resulting in clinical jaundice and/or known coagulation defects
• Major surgery within 28 days of study enrollment (other than diverting colostomy)
• History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis requiring significant intervention (eg, hospitalization, surgery, immunosuppressive medications that would, in the opinion of the investigator, preclude study therapy
• Prior known allergic reaction to 5-FU or oxaliplatin
• Known dipyrimidine dehydrogenase deficiency (DPD)
• Any evidence of distant metastases (M1)
• Pregnant or breast feeding
• Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements