Clinical trial NCT02008656: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: CAPECITABINE (ORAL)
FLUOROURACIL
LEUCOVORIN
OXALIPLATIN
Total mesorectal excision
Chemoradiation therapy
Total neoadjuvant therapy
13-213
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Colon and Rectal Surgery Inc.
name: The Cleveland Clinic
name: John Muir Health
name: Oregon Health and Science University
name: St. Joseph Hospital of Orange
name: University of California, Irvine
name: University of California, San Francisco
name: University of Chicago
name: University of South Florida
name: University of Vermont
name: University of Washington
name: Medstar Health Research Institute
name: Washington University School of Medicine
name: Creighton University Medical Center
name: The Methodist Hospital Research Institute
name: University of Rochester
name: University of Virginia
name: St. Paul's Hospital
name: St. Joseph, Florida
name: Cleveland Clinic Florida
name: University of Colorado, Denver
name: University of Michigan
First posted: 2013-12-11
Enrollment: 358
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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.

Primary outcomes:
measure: disease-free survival (DFS)
timeFrame: 3 years
Secondary outcomes:
measure: major adverse events
timeFrame: 3 years
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Orange
country: United States
facility: St. Joseph Hospital
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Walnut Creek
country: United States
facility: John Muir Health
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Tampa
country: United States
facility: University Of South Florida
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Northville
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: CHI Heath Bergan Mercy
state: Nebraska
city: Omaha
country: United States
facility: Colon and Rectal Surgery, Incorporated
state: Nebraska
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Sleepy Hollow
country: United States
facility: Memorial Sloan Kettering Cancer Center at Phelps
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: University of Washington School of Medicine
state: Washington
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Julio Garcia Aguilar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.