Trial Evaluating 3-year Disease Free Survival in Patients With Locally Advanced Rectal Cancer Treated With Chemoradiation Plus Induction or Consolidation Chemotherapy and Total Mesorectal Excision or Non-operative Management

NCT02008656 | Active Not Recruiting Phase 2

• 1 other identifier: 13-213
• Study Type: interventional
• Target: 358
• Locations: 1 country
• Sites: 26

Brief Summary

The study is designed to test the hypothesis that patients with Locally advanced rectal cancer ( LARC) treated with Total neoadjuvant therapy (TNT) and Total mesorectal excision (TME) or Non-operative management (NOM) will have an improved 3-year disease-free survival (DFS) compared to patients with similar tumors treated with Chemoradiation therapy (CRT), Total mesorectal excision (TME) and Adjuvant chemotherapy (ACT).

Conditions

Rectal Cancer

Keywords

CAPECITABINE (ORAL); FLUOROURACIL; LEUCOVORIN; OXALIPLATIN; Total mesorectal excision; Chemoradiation therapy; Total neoadjuvant therapy; 13-213

Outcome Measures

Primary Outcomes (1)

• disease-free survival (DFS)

  3-year DFS will be defined as the percentage of patients alive without recurrence of disease at 3 years measured from the date of randomization

  3 years

Secondary Outcomes (1)

• major adverse events

  3 years

Study Arms (2)

INCT

EXPERIMENTAL

Arm 1 will receive chemotherapy before chemoradiation. This is called induction neoadjuvant chemotherapy arm (INCT). The neoadjuvant chemotherapy regimen is prescribed specifically as 8 cycles of FOLFOX or 5 cycles of CapeOX over a period of approximately 15-16 weeks. Endoscopic exam (2-4 wks) after chemotherapy. If stable or response then pt will have radiation with either 5-FU or capecitabine.

Drug: Oxaliplatin (OXAL); Drug: 5-Fluorouracil (5-FU); Drug: Leucovorin; Drug: Capecitabine (Xeloda®); Radiation: intensity modulated radiotherapy (IMRT); Behavioral: Quality of Life Questionnaires; Procedure: DRE-Endoscopy

CNCT

EXPERIMENTAL

Arm 2 will receive chemoradiation before chemotherapy This is called the consolidation neoadjuvant chemotherapy arm (CNCT). Pt will have 6 weeks of chemoradiation therapy. Along with the radiation the pt will receive either 5-FU or capecitabine. 2-4 weeks after pt will have endoscopic exam and if stable or response pt will have will have 8 cycles of FOLFOX or 6 cycles of CapeOX.

Drug: Oxaliplatin (OXAL); Drug: 5-Fluorouracil (5-FU); Drug: Leucovorin; Drug: Capecitabine (Xeloda®); Radiation: intensity modulated radiotherapy (IMRT); Behavioral: Quality of Life Questionnaires; Procedure: DRE-Endoscopy

Interventions

Oxaliplatin (OXAL) DRUG

CNCT; INCT

5-Fluorouracil (5-FU) DRUG

CNCT; INCT

Leucovorin DRUG

CNCT; INCT

Capecitabine (Xeloda®) DRUG

CNCT; INCT

intensity modulated radiotherapy (IMRT) RADIATION

CNCT; INCT

Quality of Life Questionnaires BEHAVIORAL

CNCT; INCT

DRE-Endoscopy PROCEDURE

CNCT; INCT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of adenocarcinoma of the rectum
• Clinical Stage II (T3-4, N-) or Stage III (any T, N+) based on MRI
• Rectal tumor at baseline which would be considered to require complete TME
• No evidence of distant metastases
• No prior pelvic radiation therapy
• No prior chemotherapy or surgery for rectal cancer
• Age ≥ 18 years The minimum legal age of consent for select Canadian provinces is 19
• No active infections requiring systemic antibiotic treatment (oral antibiotics are acceptable at the discretion of the treating physician)
• ECOG Performance status 0-2
• Women with childbearing potential (WOCBP) who are negative for pregnancy test (urine or blood) and who agree to use effective contraceptive method. A woman of childbearing potential is defined of one who is biologically capable of becoming pregnant. Reliable contraception should be used from trial screening and must be continued throughout the study.
• Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study. Patients who do not read or understand English are eligible and may be consented according to institutional and federal regulations.
• ANC \> 1.5 cells/mm3, HGB \> 8.0 gm/dl, PLT \> 150,000/mm3 total bilirubin ≤ 1.5 x ULN (except in patients with Gilbert's Syndrome who must have total bilirubin ≤ 3.0 x ULN), AST≤ 3 x ULN, ALT ≤ 3 x ULN.

You may not qualify if:

• Recurrent rectal cancer
• Primary unresectable rectal cancer. A tumor is considered unresectable when invading adjacent organs and an en block resection will not achieve negative margins.
• Creatinine level greater than 1.5 times the upper limit of normal.
• Patients who have received prior pelvic radiotherapy.
• Patients who are unable to undergo an MRI.
• Patients with a history of any arterial thrombotic event within the past 6 months. This includes angina (stable or unstable), MI, TIA, or CVA.
• Patients with a history of venous thrombotic episodes such as deep venous thrombosis, pulmonary embolus occurring more than 6 months prior to enrollment may be considered for protocol participation, provided they are on stable doses of anticoagulant therapy. Similarly, patients who are anticoagulated for atrial fibrillation or other conditions may participate, provided they are on stable doses of anticoagulant therapy.
• Other Anticancer or Experimental Therapy. No other experimental therapies (including chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloprotease inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody or other experimental drugs) of any kind are permitted while the patient is receiving study treatment.
• WOCBP who are unwilling or unable to use an acceptable method of avoiding pregnancy for the entire study period.
• Women who are pregnant or breast-feeding.
• Patients with any other concurrent medical or psychiatric condition or disease which, in the investigator's judgment, would make them inappropriate candidates for entry into this study.
• Patients with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Colon and Rectal Surgery Inc.: collaborator
• The Cleveland Clinic: collaborator
• John Muir Health: collaborator
• Oregon Health and Science University: collaborator
• St. Joseph Hospital of Orange: collaborator
• University of California, Irvine: collaborator
• University of California, San Francisco: collaborator
• University of Chicago: collaborator
• University of South Florida: collaborator
• University of Vermont: collaborator
• University of Washington: collaborator
• Medstar Health Research Institute: collaborator
• Washington University School of Medicine: collaborator
• Creighton University Medical Center: collaborator
• The Methodist Hospital Research Institute: collaborator
• University of Rochester: collaborator
• University of Virginia: collaborator
• St. Paul's Hospital: collaborator
• St. Joseph, Florida: collaborator
• Cleveland Clinic Florida: collaborator
• University of Colorado, Denver: collaborator
• University of Michigan: collaborator

Study Sites (26)

University of California, Irvine

Irvine, California, 92697, United States

Location

St. Joseph Hospital

Orange, California, 92868-3849, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

John Muir Health

Walnut Creek, California, 94598, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

University Of South Florida

Tampa, Florida, 33620, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Michigan

Northville, Michigan, 48168, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

CHI Heath Bergan Mercy

Omaha, Nebraska, 68114, United States

Location

Colon and Rectal Surgery, Incorporated

Omaha, Nebraska, 68114, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Memorial Sloan Kettering Cancer Center at Phelps

Sleepy Hollow, New York, 10591, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

University of Washington School of Medicine

Seattle, Washington, 98109, United States

Location

Related Publications (8)

• Manca P, Chen CT, Shah F, Lee C, Domenico D, Omer D, Gonzalez S, De Bruijn I, Ahuno S, Chatila WK, Darmofal M, Tavassoly I, Widman AJ, Berger MF, Loomis B, Papaemmanuil E, Yaeger R, Zviran A, Garcia-Aguilar J, Sanchez-Vega F. Ultrasensitive ctDNA monitoring for organ preservation in patients with locally advanced rectal cancer. NPJ Precis Oncol. 2025 Dec 11;10(1):8. doi: 10.1038/s41698-025-01208-w.

  PMID: 41381715 DERIVED

• Williams H, Omer DM, Thompson HM, Lin ST, Verheij FS, Miranda J, Yuval JB, Buckley J, Marco MR, Qin LX, Dombroski DA, Kedar R, Oto A, Korngold E, Veniero JC, Gandhi S, Krishnaraj A, Jagtiani M, Ohanian K, Vu D, Hope TA, Lee S, Wasnik AP, Madhuripan N, Gollub MJ, Garcia-Aguilar J; OPRA Consortium. MRI Predicts Residual Disease and Outcomes in Watch-and-Wait Patients with Rectal Cancer. Radiology. 2024 Sep;312(3):e232748. doi: 10.1148/radiol.232748.

  PMID: 39225603 DERIVED

• Thompson HM, Omer DM, Lin S, Kim JK, Yuval JB, Verheij FS, Qin LX, Gollub MJ, Wu AJ, Lee M, Patil S, Hezel AF, Marcet JE, Cataldo PA, Polite BN, Herzig DO, Liska D, Oommen S, Friel CM, Ternent CA, Coveler AL, Hunt SR, Garcia-Aguilar J; OPRA Consortium. Organ Preservation and Survival by Clinical Response Grade in Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy: A Secondary Analysis of the OPRA Randomized Clinical Trial. JAMA Netw Open. 2024 Jan 2;7(1):e2350903. doi: 10.1001/jamanetworkopen.2023.50903.

  PMID: 38194231 DERIVED

• Verheij FS, Omer DM, Williams H, Lin ST, Qin LX, Buckley JT, Thompson HM, Yuval JB, Kim JK, Dunne RF, Marcet J, Cataldo P, Polite B, Herzig DO, Liska D, Oommen S, Friel CM, Ternent C, Coveler AL, Hunt S, Gregory A, Varma MG, Bello BL, Carmichael JC, Krauss J, Gleisner A, Guillem JG, Temple L, Goodman KA, Segal NH, Cercek A, Yaeger R, Nash GM, Widmar M, Wei IH, Pappou EP, Weiser MR, Paty PB, Smith JJ, Wu AJ, Gollub MJ, Saltz LB, Garcia-Aguilar J. Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial. J Clin Oncol. 2024 Feb 10;42(5):500-506. doi: 10.1200/JCO.23.01208. Epub 2023 Oct 26.

  PMID: 37883738 DERIVED

• Garcia-Aguilar J, Patil S, Gollub MJ, Kim JK, Yuval JB, Thompson HM, Verheij FS, Omer DM, Lee M, Dunne RF, Marcet J, Cataldo P, Polite B, Herzig DO, Liska D, Oommen S, Friel CM, Ternent C, Coveler AL, Hunt S, Gregory A, Varma MG, Bello BL, Carmichael JC, Krauss J, Gleisner A, Paty PB, Weiser MR, Nash GM, Pappou E, Guillem JG, Temple L, Wei IH, Widmar M, Lin S, Segal NH, Cercek A, Yaeger R, Smith JJ, Goodman KA, Wu AJ, Saltz LB. Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy. J Clin Oncol. 2022 Aug 10;40(23):2546-2556. doi: 10.1200/JCO.22.00032. Epub 2022 Apr 28.

  PMID: 35483010 DERIVED

• Shi DD, Mamon HJ. Playing With Dynamite? A Cautious Assessment of TNT. J Clin Oncol. 2021 Jan 10;39(2):103-106. doi: 10.1200/JCO.20.02199. Epub 2020 Oct 14. No abstract available.

  PMID: 33052753 DERIVED

• Smith JJ, Chow OS, Gollub MJ, Nash GM, Temple LK, Weiser MR, Guillem JG, Paty PB, Avila K, Garcia-Aguilar J; Rectal Cancer Consortium. 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 mesorectal excision or nonoperative management. BMC Cancer. 2015 Oct 23;15:767. doi: 10.1186/s12885-015-1632-z.

  PMID: 26497495 DERIVED

• Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, Kumar AS, Oommen S, Coutsoftides T, Hunt SR, Stamos MJ, Ternent CA, Herzig DO, Fichera A, Polite BN, Dietz DW, Patil S, Avila K; Timing of Rectal Cancer Response to Chemoradiation Consortium. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015 Aug;16(8):957-66. doi: 10.1016/S1470-2045(15)00004-2. Epub 2015 Jul 14.

  PMID: 26187751 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Oxaliplatin; Fluorouracil; Leucovorin; Capecitabine; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Julio Garcia Aguilar, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2013
• First Posted: December 11, 2013
• Study Start: November 1, 2013
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: August 27, 2025

Record last verified: 2025-08

Locations

US (26)