Clinical trial NCT01308086: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: CRC
Keywords: Cancer
colorectal cancer
adjuvant chemotherapy
capecitabine
oxaliplatin
5 fluorouracil
Lead sponsor: Hellenic Oncology Research Group
Sponsor class: OTHER
Collaborators: name: University Hospital of Crete
First posted: 2011-03-03
Enrollment: 2000
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 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.

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

Primary outcomes:
measure: Relapse Free Survival
timeFrame: 3-years
Secondary outcomes:
measure: Overall Survival
timeFrame: 3-years
measure: Safety Profil according to NCI-CTAE v 3.0
timeFrame: q2w
Other outcomes:
Locations:
city: Heraklion
country: Greece
facility: University Hospital of Crete, Dep of Medical Oncology
Study officials:
affiliation: University Hospital of Crete, Dep of Medical Oncology
name: John Souglakos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Crete, Dep of Medical Oncology
name: Vassilis Georgoulias, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.