This is a randomized Phase II trial investigating the optimal timing of delivery of neoadjuvant therapy, in order to maximize the proportion of patients with distal rectal cancer who may be cured while preserving the rectum. Patients with distal rectal cancer who are candidates for a coloanal anastomosis or abdominoperineal excision will be randomized to receive neoadjuvant chemotherapy before (induction arm) or after (consolidation arm) chemoradiation. Patients will be restaged 4 to 6 weeks after completing all neoadjuvant therapy. Those with incomplete tumor response will undergo a total mesorectal excision. Patients with complete tumor response will be observed, and will have a total mesorectal excision only if they develop signs of tumor relapse during follow-up.

Public Health Relevance

The treatment of rectal cancer with neoadjuvant chemoradiation, total mesorectal excision, and postoperative adjuvant chemotherapy results in excellent local tumor control. However, many patients still die as a consequence of distant metastasis. In addition, long-term survivors have diminished quality of life, due primarily to removal of the rectum. This study aims to increase survival by optimizing the use of neoadjuvant chemotherapy, and to improve quality of life by preserving the rectum in patients with a sustained clinical response to neoadjuvant therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA182551-03
Application #
9001326
Study Section
Special Emphasis Panel (ZCA1-RPRB-0 (O1))
Program Officer
Timmer, William C
Project Start
2014-02-01
Project End
2019-01-31
Budget Start
2016-02-01
Budget End
2017-01-31
Support Year
3
Fiscal Year
2016
Total Cost
$718,852
Indirect Cost
$314,321
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Wasserman, Isaac; Lee, Lik Hang; Ogino, Shuji et al. (2018) SMAD4 loss in colorectal cancer patients correlates with recurrence, loss of immune infiltrate, and chemoresistance. Clin Cancer Res :
Lynn, Patricio B; Renfro, Lindsay A; Carrero, Xiomara W et al. (2017) Anorectal Function and Quality of Life in Patients With Early Stage Rectal Cancer Treated With Chemoradiation and Local Excision. Dis Colon Rectum 60:459-468
Chow, Oliver S; Kuk, Deborah; Keskin, Metin et al. (2016) KRAS and Combined KRAS/TP53 Mutations in Locally Advanced Rectal Cancer are Independently Associated with Decreased Response to Neoadjuvant Therapy. Ann Surg Oncol 23:2548-55
Widmar, M; Keskin, M; Beltran, P et al. (2016) Incisional hernias after laparoscopic and robotic right colectomy. Hernia 20:723-8
Lee, Lik Hang; Cavalcanti, Marcela S; Segal, Neil H et al. (2016) Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma. Mod Pathol 29:1433-1442
Smith, J Joshua; Chow, Oliver S; Gollub, Marc J et al. (2015) Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total BMC Cancer 15:767
Probst, Christian P; Becerra, Adan Z; Aquina, Christopher T et al. (2015) Extended Intervals after Neoadjuvant Therapy in Locally Advanced Rectal Cancer: The Key to Improved Tumor Response and Potential Organ Preservation. J Am Coll Surg 221:430-40
Garcia-Aguilar, Julio; Renfro, Lindsay A; Chow, Oliver S et al. (2015) Organ preservation for clinical T2N0 distal rectal cancer using neoadjuvant chemoradiotherapy and local excision (ACOSOG Z6041): results of an open-label, single-arm, multi-institutional, phase 2 trial. Lancet Oncol 16:1537-1546
Smith, J Joshua; Garcia-Aguilar, Julio (2015) Advances and challenges in treatment of locally advanced rectal cancer. J Clin Oncol 33:1797-808