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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by Memorial Sloan Kettering Cancer Center
Sponsor:
Collaborators:
Colon and Rectal Surgery Inc.
The Cleveland Clinic
John Muir Health
Oregon Health and Science University
St. Joseph Hospital of Orange
University of Calgary
University of California, Irvine
University of California, San Francisco
University of Chicago
University of South Florida
University of Vermont
University of Washington
Washington Hospital Center
Washington University School of Medicine
Bergan Mercy Medical Centere
The Methodist Hospital System
University of Rochester
University of Virginia
St. Paul's Hospital
St. Joseph, Florida
Cleveland Clinic Florida
University of Colorado, Aurora
University of Michigan
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT02008656
First received: November 27, 2013
Last updated: April 28, 2016
Last verified: April 2016
  Purpose
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).

Condition Intervention Phase
Rectal Cancer
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
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Multicenter Randomized 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan Kettering Cancer Center:

Primary Outcome Measures:
  • disease-free survival (DFS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • major adverse events [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Adverse events will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.


Estimated Enrollment: 222
Study Start Date: November 2013
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
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
Experimental: 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.
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02008656

Contacts
Contact: Julio Garcia Aguilar, MD PhD 212-639-5117
Contact: Leonard Saltz, MD 646-888-4181

  Show 25 Study Locations
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Colon and Rectal Surgery Inc.
The Cleveland Clinic
John Muir Health
Oregon Health and Science University
St. Joseph Hospital of Orange
University of Calgary
University of California, Irvine
University of California, San Francisco
University of Chicago
University of South Florida
University of Vermont
University of Washington
Washington Hospital Center
Washington University School of Medicine
Bergan Mercy Medical Centere
The Methodist Hospital System
University of Rochester
University of Virginia
St. Paul's Hospital
St. Joseph, Florida
Cleveland Clinic Florida
University of Colorado, Aurora
University of Michigan
Investigators
Principal Investigator: Julio Garcia Aguilar, MD, PhD Memorial Sloan Kettering Cancer Center
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT02008656     History of Changes
Other Study ID Numbers: 13-213 
Study First Received: November 27, 2013
Last Updated: April 28, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan Kettering Cancer Center:
CAPECITABINE (ORAL)
FLUOROURACIL
LEUCOVORIN
OXALIPLATIN
Total mesorectal excision
Chemoradiation therapy
Total neoadjuvant therapy
13-213

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Capecitabine
Fluorouracil
Oxaliplatin
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on May 02, 2016