Adjuvant Therapy(3 vs. 6 Months) With the FOLFOX 4 or XELOX for Stage II or Stage III Colon Cancer

• ClinicalTrials.gov Identifier: NCT01308086
• Recruitment Status: Unknown
• First Posted: March 3, 2011
• Last Update Posted: August 9, 2017
• Sponsor: Hellenic Oncology Research Group
• Collaborator: University Hospital of Crete
• Information provided by (Responsible Party): Hellenic Oncology Research Group

Tracking Information

• First Submitted Date: March 1, 2011
• First Posted Date: March 3, 2011
• Last Update Posted Date: August 9, 2017
• Study Start Date: October 2010
• Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 2, 2011): Relapse Free Survival [ Time Frame: 3-years ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 2, 2011)

• Overall Survival [ Time Frame: 3-years ]
• Safety Profil according to NCI-CTAE v 3.0 [ Time Frame: q2w ]
  Percentage (%) of treatments delays and interaptions in each arm Percentage (%) of dose received versus planned dose in each arm

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Adjuvant Therapy(3 vs. 6 Months) With the FOLFOX 4 or XELOX for Stage II or Stage III Colon Cancer
• Official Title: A Multicenter Trial Investigating the Duration of Adjuvant Therapy(3 vs. 6 Months) With the FOLFOX 4 or XELOX Regimen for Patients With High Risk Stage II or Stage III Colon Cancer
• Brief Summary: The purpose of this study is to compare whether a 3-month treatment is at least not inferior to a 6-month treatment (FOLFOX-4 6 vs. 12 cycles or XELOX 4 cycles vs. 8 cycles) in terms of RFS in patients with high risk stage II or stage III radically resected colon cancer.

Detailed Description

Six months of adjuvant chemotherapy with 5-FU and oxaliplatin for patients with stage III colon cancer is the world-wide standard of care, based on the MOSAIC and C-07 trials. However, it leads to significant cost, toxicity, and inconvenience. In particular, the onset of oxaliplatin induced cumulative dose-dependent neuropathies is a significant issue. The ability to maintain efficacy with a reduced duration of therapy would have clear advantage to patients, to providers, and to the health care system.

Multiple large trials in the 1990s demonstrated that the previous standard of 12 months of therapy could be reduced to 6 months. A single small trial with 5-FU alone demonstrated similar outcomes for 3 versus 6 months of therapy. Thus, it is proposed to definitively evaluate the non-inferiority of 3 months of oxaliplatin-based adjuvant chemotherapy versus the current standard of 6 months. The primary endpoint will be disease-free survival (DFS).

It is essential to have sufficient power to eliminate the possibility of clinically meaningful inferiority of 3 months of therapy: a huge number of patients will be necessary. Previous efforts and experience have conclusively demonstrated that in colon cancer, a single, global trial is impractical. Consequently, an international, prospective pooled analysis will be performed, gathering data of independent trials run in different countries, to answer the single primary hypothesis that 3 months of adjuvant therapy with FOLFOX/XELOX is non-inferior to the current standard of 6 months. Among six planned countries, the Greek intergroup will conduct one of these trials.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: CRC

Intervention

• Drug: 5-Fluorouracil
  5-FU 400mg/m2 Bolus and then 22 hours 5-FU 600mg/m2 IV, days 1 & 2, q2w, for 12 cycles
  Other Name: 5-FU
• Drug: Leucovorin
  Leucovorin 200mg/m2 IV in 2 hours, days 1 & 2, q2w, for 12 cycles
• Drug: Oxaliplatin
  Oxaliplatin 85mg/m2 in 2 hours IV, day 1, q2w, for 12 cycles
  Other Name: LoHP
• Drug: Capecitabine
  Capecitabine 1000 mg/m2 X 2 ,days 1-14, q2w, for 8 cycles
  Other Name: Xeloda
• Drug: Oxaliplatin
  Oxaliplatin 130 mg/m2 in 2 hours IV, day 1, q2w, for 8 cycles
  Other Name: LoHP
• Drug: 5-Fluorouracil
  5-FU 400mg/m2 Bolus and then 22 hours 5-FU 600mg/m2 IV, days 1 & 2, q2w, for 6 cycles
  Other Name: 5-FU
• Drug: Leucovorin
  Leucovorin 200mg/m2 IV in 2 hours, days 1 & 2, q2w, for 6 cycles
• Drug: Capecitabine
  Capecitabine 1000 mg/m2 X 2 ,days 1-14, q2w, for 4 cycles
  Other Name: Xeloda
• Drug: Oxaliplatin
  Oxaliplatin 130 mg/m2 in 2 hours IV, day 1, q2w, for 4 cycles
  Other Name: LoHP
• Drug: Oxaliplatin
  Oxaliplatin 85mg/m2 in 2 hours IV, day 1, q2w, for 6 cycles
  Other Name: LoHP

Study Arms

• Active Comparator: FOLFOX 4 - 6months or XELOX -6months
  Interventions:

  • Drug: 5-Fluorouracil
  • Drug: Leucovorin
  • Drug: Oxaliplatin
  • Drug: Capecitabine
  • Drug: Oxaliplatin
• Experimental: FOLFOX4 -3months or XELOX -3months
  Interventions:

  • Drug: 5-Fluorouracil
  • Drug: Leucovorin
  • Drug: Capecitabine
  • Drug: Oxaliplatin
  • Drug: Oxaliplatin

Publications *

• Gallois C, Shi Q, Meyers JP, Iveson T, Alberts SR, de Gramont A, Sobrero AF, Haller DG, Oki E, Shields AF, Goldberg RM, Kerr R, Lonardi S, Yothers G, Kelly C, Boukovinas I, Labianca R, Sinicrope FA, Souglakos I, Yoshino T, Meyerhardt JA, Andre T, Papamichael D, Taieb J. Prognostic Impact of Early Treatment and Oxaliplatin Discontinuation in Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 11 Adjuvant Trials. J Clin Oncol. 2023 Feb 1;41(4):803-815. doi: 10.1200/JCO.21.02726. Epub 2022 Oct 28.
• Iveson TJ, Sobrero AF, Yoshino T, Souglakos I, Ou FS, Meyers JP, Shi Q, Grothey A, Saunders MP, Labianca R, Yamanaka T, Boukovinas I, Hollander NH, Galli F, Yamazaki K, Georgoulias V, Kerr R, Oki E, Lonardi S, Harkin A, Rosati G, Paul J. Duration of Adjuvant Doublet Chemotherapy (3 or 6 months) in Patients With High-Risk Stage II Colorectal Cancer. J Clin Oncol. 2021 Feb 20;39(6):631-641. doi: 10.1200/JCO.20.01330. Epub 2021 Jan 13. Erratum In: J Clin Oncol. 2021 May 20;39(15):1691.
• Souglakos J, Boukovinas I, Kakolyris S, Xynogalos S, Ziras N, Athanasiadis A, Androulakis N, Christopoulou A, Vaslamatzis M, Ardavanis A, Emmanouilides C, Bompolaki I, Kourousis C, Makrantonakis P, Christofyllakis C, Athanasiadis E, Kentepozidis N, Karampeazis A, Katopodi U, Anagnosopoulos A, Papadopoulos G, Prinarakis E, Kalisperi A, Mavroudis D, Georgoulias V. Three- versus six-month adjuvant FOLFOX or CAPOX for high-risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) project. Ann Oncol. 2019 Aug 1;30(8):1304-1310. doi: 10.1093/annonc/mdz193.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: March 2, 2011): 2000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2017
• Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically- - confirmed adenocarcinoma of the colon or rectum stage III or stage with at least one of the follow characteristics T4 tumours, undifferentiated tumor grade >3, bowel obstruction or perforation, vascular or lymphatic or perineural invasion, <12 nodes examined, Stage IV.
• Signed written informed consent
• Randomization between 2 -8 weeks after curative surgery
• Age >18 years
• ECOG performance Status 0-1
• Pretreatment CEA within UNL
• Post-menopausal women or women willing to accept the use of an effective contraception. Pre-menopausal women should have a negative pregnancy test within 72 hours prior to randomization
• Men should also accept to use an effective contraception
• R0 resections

Exclusion Criteria:

• Evidence of metastatic disease (including presence of tumor cells in ascites or peritoneal carcinomatosis resected "en bloc")
• Evidence of other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix)
• No pregnant or lactating women
• Presence of clinically relevant cardiovascular disease
• Presenc of medical history or current evidence of CNS disease
• Presence of peripheral neuropathy ≤ grade 1 (CTCAE v. 3.0)
• History of clinically relevant psychiatric disability, precluding informed consent

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Greece

Administrative Information

• NCT Number: NCT01308086
• Other Study ID Numbers: CT/09.12
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hellenic Oncology Research Group
• Original Responsible Party: John Sougklakos, University Hospital of Crete
• Current Study Sponsor: Hellenic Oncology Research Group
• Original Study Sponsor: Same as current
• Collaborators: University Hospital of Crete

Investigators

• Principal Investigator: John Souglakos, MD; University Hospital of Crete, Dep of Medical Oncology
• Study Chair: Vassilis Georgoulias, MD; University Hospital of Crete, Dep of Medical Oncology

• PRS Account: Hellenic Oncology Research Group
• Verification Date: August 2017