total neoadjuvant therapy with mfolfox and short-course radiation in resectable rectal cancer

Conditions: Rectal Cancer

Summary: this is phase 2 trial of neoadjuvant therapy and short-course radiotherapy in resectable rectal cancer.

this trial involves 4 cycles of systemic chemotherapy followed by short-course rt with concurrent 5-fu neoadjuvant chemoradiotherapy (crt) and subsequent consolidation with 4 cycles of systemic chemotherapy prior to surgery or, for those who achieve ccr, the option of non-operative active surveillance.three-year disease free survival (dfs) defined as the percentage of patients alive without recurrence of disease at 3 years measured from the date of clinical complete response (ccr) or date of total mesorectal excision (tme) at surgery (whichever is earlier).

Eligibility criteria:
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, unless patient presents with an obstructing lesion * within 30 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 or mri * 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) ≥ 1,200 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 ≤ 2.5 uln * calculated creatinine clearance (crcl) \> 30 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, that in the opinion of the treating medical oncologist would preclude them from receiving systemic therapy with 5-fluorouracil, leucovorin or oxaliplatin. * serious (ie, ≥ grade 3) uncontrolled infection * pulmonary or respiratory condition that, in the opinion of the treating medical oncologist would preclude them from receiving systemic therapy with 5-fluorouracil, leucovorin or oxaliplatin. * 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-fluorouracil, leucovorin, 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

Keywords: resectable rectal