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

August 8, 2017 updated by: Hellenic Oncology Research Group

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

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.

Study Overview

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

Enrollment (Actual)

2000

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Heraklion, Greece
        • University Hospital of Crete, Dep of Medical Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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:
  • 5-FU
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:
  • LoHP
Capecitabine 1000 mg/m2 X 2 ,days 1-14, q2w, for 8 cycles
Other Names:
  • Xeloda
Oxaliplatin 130 mg/m2 in 2 hours IV, day 1, q2w, for 8 cycles
Other Names:
  • LoHP
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
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:
  • Xeloda
Oxaliplatin 130 mg/m2 in 2 hours IV, day 1, q2w, for 4 cycles
Other Names:
  • LoHP
Oxaliplatin 85mg/m2 in 2 hours IV, day 1, q2w, for 6 cycles
Other Names:
  • LoHP
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:
  • 5-FU
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:
  • LoHP
Capecitabine 1000 mg/m2 X 2 ,days 1-14, q2w, for 8 cycles
Other Names:
  • Xeloda
Oxaliplatin 130 mg/m2 in 2 hours IV, day 1, q2w, for 8 cycles
Other Names:
  • LoHP
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
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:
  • Xeloda
Oxaliplatin 130 mg/m2 in 2 hours IV, day 1, q2w, for 4 cycles
Other Names:
  • LoHP
Oxaliplatin 85mg/m2 in 2 hours IV, day 1, q2w, for 6 cycles
Other Names:
  • LoHP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Relapse Free Survival
Time Frame: 3-years
3-years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 3-years
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
q2w

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2010

Primary Completion (Anticipated)

November 1, 2017

Study Completion (Anticipated)

December 1, 2017

Study Registration Dates

First Submitted

March 1, 2011

First Submitted That Met QC Criteria

March 2, 2011

First Posted (Estimate)

March 3, 2011

Study Record Updates

Last Update Posted (Actual)

August 9, 2017

Last Update Submitted That Met QC Criteria

August 8, 2017

Last Verified

August 1, 2017

More Information

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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