- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01308086
Adjuvant Therapy(3 vs. 6 Months) With the FOLFOX 4 or XELOX for Stage II or Stage III Colon Cancer
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
Study Overview
Status
Conditions
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
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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-
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Heraklion, Greece
- University Hospital of Crete, Dep of Medical Oncology
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: FOLFOX 4 - 6months or XELOX -6months
|
5-FU 400mg/m2 Bolus and then 22 hours 5-FU 600mg/m2 IV, days 1 & 2, q2w, for 12 cycles
Other Names:
Leucovorin 200mg/m2 IV in 2 hours, days 1 & 2, q2w, for 12 cycles
Oxaliplatin 85mg/m2 in 2 hours IV, day 1, q2w, for 12 cycles
Other Names:
Capecitabine 1000 mg/m2 X 2 ,days 1-14, q2w, for 8 cycles
Other Names:
Oxaliplatin 130 mg/m2 in 2 hours IV, day 1, q2w, for 8 cycles
Other Names:
5-FU 400mg/m2 Bolus and then 22 hours 5-FU 600mg/m2 IV, days 1 & 2, q2w, for 6 cycles
Other Names:
Leucovorin 200mg/m2 IV in 2 hours, days 1 & 2, q2w, for 6 cycles
Capecitabine 1000 mg/m2 X 2 ,days 1-14, q2w, for 4 cycles
Other Names:
Oxaliplatin 130 mg/m2 in 2 hours IV, day 1, q2w, for 4 cycles
Other Names:
Oxaliplatin 85mg/m2 in 2 hours IV, day 1, q2w, for 6 cycles
Other Names:
|
Experimental: FOLFOX4 -3months or XELOX -3months
|
5-FU 400mg/m2 Bolus and then 22 hours 5-FU 600mg/m2 IV, days 1 & 2, q2w, for 12 cycles
Other Names:
Leucovorin 200mg/m2 IV in 2 hours, days 1 & 2, q2w, for 12 cycles
Oxaliplatin 85mg/m2 in 2 hours IV, day 1, q2w, for 12 cycles
Other Names:
Capecitabine 1000 mg/m2 X 2 ,days 1-14, q2w, for 8 cycles
Other Names:
Oxaliplatin 130 mg/m2 in 2 hours IV, day 1, q2w, for 8 cycles
Other Names:
5-FU 400mg/m2 Bolus and then 22 hours 5-FU 600mg/m2 IV, days 1 & 2, q2w, for 6 cycles
Other Names:
Leucovorin 200mg/m2 IV in 2 hours, days 1 & 2, q2w, for 6 cycles
Capecitabine 1000 mg/m2 X 2 ,days 1-14, q2w, for 4 cycles
Other Names:
Oxaliplatin 130 mg/m2 in 2 hours IV, day 1, q2w, for 4 cycles
Other Names:
Oxaliplatin 85mg/m2 in 2 hours IV, day 1, q2w, for 6 cycles
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Relapse Free Survival
Time Frame: 3-years
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3-years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: 3-years
|
3-years
|
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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
|
q2w
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Collaborators and Investigators
Sponsor
Collaborators
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
Publications and helpful links
General 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. 2022 Oct 28:JCO2102726. doi: 10.1200/JCO.21.02726. Online ahead of print.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Colorectal Neoplasms
- Colonic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Micronutrients
- Vitamins
- Antidotes
- Vitamin B Complex
- Fluorouracil
- Capecitabine
- Oxaliplatin
- Leucovorin
- Levoleucovorin
Other Study ID Numbers
- CT/09.12
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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