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

Sponsor

Hellenic Oncology Research Group (Other)

Overall Status

Unknown status

CT.gov ID

NCT01308086

Collaborator

University Hospital of Crete (Other)

2,000

Enrollment

Location

Arms

Duration (Months)

23.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
CRC	Drug: 5-Fluorouracil Drug: Leucovorin Drug: Oxaliplatin Drug: Capecitabine Drug: Oxaliplatin Drug: 5-Fluorouracil Drug: Leucovorin Drug: Capecitabine Drug: Oxaliplatin Drug: Oxaliplatin	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

2000 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Oct 1, 2010

Anticipated Primary Completion Date :

Nov 1, 2017

Anticipated Study Completion Date :

Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: FOLFOX 4 - 6months or XELOX -6months	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 Names: 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 Names: LoHP Drug: Capecitabine Capecitabine 1000 mg/m2 X 2 ,days 1-14, q2w, for 8 cycles Other Names: Xeloda Drug: Oxaliplatin Oxaliplatin 130 mg/m2 in 2 hours IV, day 1, q2w, for 8 cycles Other Names: LoHP
Experimental: FOLFOX4 -3months or XELOX -3months	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 Names: 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 Names: Xeloda Drug: Oxaliplatin Oxaliplatin 130 mg/m2 in 2 hours IV, day 1, q2w, for 4 cycles Other Names: LoHP Drug: Oxaliplatin Oxaliplatin 85mg/m2 in 2 hours IV, day 1, q2w, for 6 cycles Other Names: LoHP

Arm

Intervention/Treatment

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

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 Names:

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 Names:

LoHP

Drug: Capecitabine

Capecitabine 1000 mg/m2 X 2 ,days 1-14, q2w, for 8 cycles

Other Names:

Xeloda

Drug: Oxaliplatin

Oxaliplatin 130 mg/m2 in 2 hours IV, day 1, q2w, for 8 cycles

Other Names:

LoHP

Experimental: FOLFOX4 -3months or XELOX -3months

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 Names:

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 Names:

Xeloda

Drug: Oxaliplatin

Oxaliplatin 130 mg/m2 in 2 hours IV, day 1, q2w, for 4 cycles

Other Names:

LoHP

Drug: Oxaliplatin

Oxaliplatin 85mg/m2 in 2 hours IV, day 1, q2w, for 6 cycles

Other Names:

LoHP

Outcome Measures

Primary Outcome Measures

Relapse Free Survival [3-years]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital of Crete, Dep of Medical Oncology	Heraklion		Greece

Sponsors and Collaborators

Hellenic Oncology Research Group
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