Short Course Radiation Therapy and Combination Chemotherapy for the Treatment of Stage II-III Rectal Cancer

PRIMARY OBJECTIVE:

I. Complete clinical response (cCR) rate of patients with clinical T3 and/or node-positive M0 rectal cancer being treated with short-course radiation therapy (SCRT) followed by 16 weeks of modified leucovorin, fluorouracil, and oxaliplatin (mFOLFOX)/capecitabine and oxaliplatin (CapeOX).

SECONDARY OBJECTIVES:

I. 1-year local recurrence free survival and 1-year progression free survival of the entire cohort, the cohort that initially undergoes non-operative management (NOM), and the cohort that initially undergoes total mesorectal excision (TME).

II. Physician-reported acute and late >= grade 3 toxicity rates.

III. 1-year post-treatment patient health-related quality of life and anorectal function as per Patient Reported Outcomes Measurement and Information System (PROMIS).

IV. Explore how Signatera’s residual disease test correlates with patient’s cCR rates, local recurrence, progression-free, and overall survival rates.

V. Explore radiomics features from longitudinal diffusion weighted magnetic resonance imaging (MRI) (diffusion weighted imaging [DWI]) data and build a predictive model for treatment effect (complete response) in rectal cancer patients undergoing SCRT.

OUTLINE:

Patients undergo SCRT in the form of intensity-modulated radiation therapy (IMRT) over 5 fractions daily for 5 consecutive days. Beginning 11-18 days after the last day of radiation therapy, patients receive either oxaliplatin intravenously (IV) and leucovorin IV on day 1 and fluorouracil IV on days 1-3 (mFOLFOX6) or oxaliplatin IV on day 1 and capecitabine orally (PO) twice daily (BID) on days 1-14 (CapeOX). Treatment with mFOLFOX6 repeats every 2 weeks for up to 8 cycles, and treatment with CapeOX repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. At 8-12 weeks after completion of all therapy, patients undergo digital rectal exam (DRE), endoscopy, and MRI for re-staging. Patients with residual tumor undergo TME and patients with cCR undergo NOM.

After completion of study treatment, patients who underwent NOM are followed up every 3 months for 2 years, then every 6 months thereafter. TME patients are followed up every 6 months for 2 years, then yearly thereafter for 5 years.