Neoadjuvant Therapy for Localized Rectal Adenocarcinoma

Summary

This study is a prospective, single-arm, single-center study of investigator's choice of total neoadjuvant therapy (TNT) or neoadjuvant chemoradiation in locally advanced rectal cancer. The standard of care for rectal adenocarcinomas that are triiodothyronine-thyroxine (T3-T4) or node positive has generally been comprised of neoadjuvant chemoradiation, followed by surgical resection and then adjuvant chemotherapy. More recently, TNT, comprised of neoadjuvant chemotherapy and chemoradiation followed by surgical resection, has been increasingly used as a standard therapy approach. While the use of TNT is increasingly common, prospective study of outcomes following TNT has been limited. Moreover, there are not any biomarkers known at this time that impact clinical decision-making or personalization of therapy in the treatment of rectal cancer. In this study, we will collect pre-treatment rectal adenocarcinoma specimens and determine clinical outcome, including pathologic complete response rate, post-treatment pathologic downstaging rate, recurrence-free survival (RFS), overall survival (OS) and neoadjuvant rectal score, among patients who are treated with standard neoadjuvant chemoradiation or TNT, with an aim to investigate how baseline biomarkers and changes in biomarkers with standard therapies may be associated with, and modulate, clinical outcomes.

Conditions

• Rectal Adenocarcinoma

Interventions

OTHER

Chemoradiation

Subjects will receive neoadjuvant chemoradiation per standard of care. This is typically comprised of radiotherapy of 5040 cGy (centigray) with concurrent capecitabine 825 mg/m2 by mouth (po) two times daily (bid) (typically rounded to the nearest 500 mg dose) or infusional 5-fluorouracil (5FU). However, dosing and administration are at the discretion of the treating medical and radiation oncologist.

RADIATION

short course radiation therapy

An acceptable alternative approach is short-course radiation therapy per standard of care, which is typically comprised of radiotherapy of 25 Gy (gray) in 5 fractions, with surgery within 1 week of completion of therapy or delayed for 6-8 weeks. Selection of the optimal radiation therapy approach is at the discretion of the treating medical oncologist, radiation oncologist, and surgical oncologist. However, generally, short-course radiation therapy is not recommended for low-lying tumors less than 5 centimeters (cm) from the anal verge.

DRUG

mFOLFOX6

possible consolidative neo-adjuvant chemotherapy. This treatment is at the discretion of the treating medical oncologist, radiation oncologist, and surgical oncologist.

DRUG

CAPOX

possible consolidative neo-adjuvant chemotherapy. This treatment is at the discretion of the treating medical oncologist, radiation oncologist, and surgical oncologist.

DRUG

fluoropyrimidine +/- oxaliplatin

possible adjuvant chemotherapy regimen. Subjects who do not receive preoperative mFOLFOX6 or CAPOX typically receive postoperative adjuvant chemotherapy with a fluoropyrimidine +/- oxaliplatin for an additional 16-18 weeks of therapy, if permitted based on recovery after surgical resection and post-surgical performance status. This treatment is at the discretion of the treating medical oncologist. Subjects will remain on study regardless of postoperative therapy administration or duration.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center

  lead OTHER

Principal Investigators

• Michael S Lee, MD · UNC Lineberger Comprehensive Cancer Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

99 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-08-13

Primary Completion

2022-05-31

Completion

2025-05-31

FDA Drug

Yes

Countries

• United States

Study Locations