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

NCT ID: NCT02008656

Last Updated: 2025-08-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

358 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-11-30

Study Completion Date

2026-11-30

Brief Summary

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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).

Detailed Description

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Conditions

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Rectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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INCT

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.

Group Type EXPERIMENTAL

Oxaliplatin (OXAL)

Intervention Type DRUG

5-Fluorouracil (5-FU)

Intervention Type DRUG

Leucovorin

Intervention Type DRUG

Capecitabine (Xeloda®)

Intervention Type DRUG

intensity modulated radiotherapy (IMRT)

Intervention Type RADIATION

Quality of Life Questionnaires

Intervention Type BEHAVIORAL

DRE-Endoscopy

Intervention Type PROCEDURE

CNCT

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.

Group Type EXPERIMENTAL

Oxaliplatin (OXAL)

Intervention Type DRUG

5-Fluorouracil (5-FU)

Intervention Type DRUG

Leucovorin

Intervention Type DRUG

Capecitabine (Xeloda®)

Intervention Type DRUG

intensity modulated radiotherapy (IMRT)

Intervention Type RADIATION

Quality of Life Questionnaires

Intervention Type BEHAVIORAL

DRE-Endoscopy

Intervention Type PROCEDURE

Interventions

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Oxaliplatin (OXAL)

Intervention Type DRUG

5-Fluorouracil (5-FU)

Intervention Type DRUG

Leucovorin

Intervention Type DRUG

Capecitabine (Xeloda®)

Intervention Type DRUG

intensity modulated radiotherapy (IMRT)

Intervention Type RADIATION

Quality of Life Questionnaires

Intervention Type BEHAVIORAL

DRE-Endoscopy

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Colon and Rectal Surgery Inc.

INDUSTRY

Sponsor Role collaborator

The Cleveland Clinic

OTHER

Sponsor Role collaborator

John Muir Health

OTHER

Sponsor Role collaborator

Oregon Health and Science University

OTHER

Sponsor Role collaborator

St. Joseph Hospital of Orange

OTHER

Sponsor Role collaborator

University of California, Irvine

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role collaborator

University of Chicago

OTHER

Sponsor Role collaborator

University of South Florida

OTHER

Sponsor Role collaborator

University of Vermont

OTHER

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role collaborator

Medstar Health Research Institute

OTHER

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role collaborator

Creighton University Medical Center

OTHER

Sponsor Role collaborator

The Methodist Hospital Research Institute

OTHER

Sponsor Role collaborator

University of Rochester

OTHER

Sponsor Role collaborator

University of Virginia

OTHER

Sponsor Role collaborator

St. Paul's Hospital

UNKNOWN

Sponsor Role collaborator

St. Joseph, Florida

UNKNOWN

Sponsor Role collaborator

Cleveland Clinic Florida

OTHER

Sponsor Role collaborator

University of Colorado, Denver

OTHER

Sponsor Role collaborator

University of Michigan

OTHER

Sponsor Role collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Julio Garcia Aguilar, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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University of California, Irvine

Irvine, California, United States

Site Status

St. Joseph Hospital

Orange, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

John Muir Health

Walnut Creek, California, United States

Site Status

University of Colorado

Aurora, Colorado, United States

Site Status

Washington Hospital Center

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

Site Status

University Of South Florida

Tampa, Florida, United States

Site Status

Cleveland Clinic Florida

Weston, Florida, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

University of Michigan

Northville, Michigan, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

CHI Heath Bergan Mercy

Omaha, Nebraska, United States

Site Status

Colon and Rectal Surgery, Incorporated

Omaha, Nebraska, United States

Site Status

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Site Status

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

Site Status

Memorial Sloan Kettering Commack

Commack, New York, United States

Site Status

Memorial Sloan Kettering Westchester

Harrison, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center at Phelps

Sleepy Hollow, New York, United States

Site Status

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

University of Vermont Medical Center

Burlington, Vermont, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

University of Washington School of Medicine

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 39225603 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38194231 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37883738 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35483010 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33052753 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26497495 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26187751 (View on PubMed)

Related Links

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http://www.mskcc.org/

Memorial Sloan Kettering Cancer Center

Other Identifiers

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13-213

Identifier Type: -

Identifier Source: org_study_id

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