Chemotherapy with Radiation for the Treatment of Rectal Cancer

PRIMARY OBJECTIVE:

I. To determine the maximal tolerated dose (MTD) of dose-escalated hypofractionated radiotherapy (RT), in patients with locally advanced rectal cancer treated with RT, FOLFOX (fluorouracil [5-FU], oxaliplatin, and leucovorin) or CAPOX (capecitabine, oxaliplatin ) chemotherapy and selective omission of surgery.

SECONDARY OBJECTIVES:

I. To evaluate the rate of clinical complete and near complete response to radiation and chemotherapy.

II. To determine the organ preservation rate at 1 year after radiotherapy and FOLFOX or CAPOX chemotherapy.

III. To evaluate locoregional recurrence, defined as time between date of therapy initiation and date of local progression.

IV. To evaluate disease-free survival (DFS), defined as the time between date of therapy completion and the first date of documented disease progression, or death.

V. For patients undergoing surgery, to evaluate the rate of R0 resection, defined as a negative surgical margin at time of total mesorectal excision.

VI. To evaluate the rate of distant failure, defined as development of disease outside of the pelvis.

EXPLORATORY OBJECTIVES:

I. To evaluate the feasibility of serial circulating tumor deoxyribonucleic acid (DNA) profiles in plasma to monitor response to chemotherapy and radiotherapy.

II. To evaluate the performance of magnetic resonance imaging (MRI) pre-, mid- and post-radiotherapy and chemotherapy to assess its ability predict treatment response and identify patients who may benefit from NOM.

III. To assess the immunomodulatory effects of radiotherapy on the tumor microenvironment and circulating immune effector cells.

IV. To collect serial fecal samples of patients to assess the association between changes in gut microbiome and clinical outcomes.

V. To assess quality of life in patients undergoing radiotherapy and chemotherapy using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire and Wexner incontinence score.

OUTLINE:

Patients receiving FOLFOX chemotherapy receive oxaliplatin intravenously (IV), leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on day 1. Treatment repeats every 2 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy at weeks 4, 8, 12, 16, and 20 in the absence of disease progression or unacceptable toxicity. Patients receiving CAPOX chemotherapy receive capecitabine twice daily (BID) on days 1-14 and oxaliplatin IV on day 1. Treatment repeats every 3 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy at weeks 6, 9, 12, 15, and 18 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 1 year or until death.