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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Hellenic Oncology Research Group
Sponsor:
Collaborator:
University Hospital of Crete
Information provided by (Responsible Party):
Hellenic Oncology Research Group
ClinicalTrials.gov Identifier:
NCT01308086
First received: March 1, 2011
Last updated: June 21, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
CRC
Drug: 5-Fluorouracil
Drug: Leucovorin
Drug: Oxaliplatin
Drug: Capecitabine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Hellenic Oncology Research Group:

Primary Outcome Measures:
  • Relapse Free Survival [ Time Frame: 3-years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 3-years ] [ Designated as safety issue: No ]
  • Safety Profil according to NCI-CTAE v 3.0 [ Time Frame: q2w ] [ Designated as safety issue: Yes ]
    Percentage (%) of treatments delays and interaptions in each arm Percentage (%) of dose received versus planned dose in each arm


Estimated Enrollment: 2000
Study Start Date: October 2010
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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
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 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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01308086

Contacts
Contact: Dora Hatzidaki +302810392570 dorachat@med.uoc.gr
Contact: Ioannis Athanassakis +302810392783 dclintrials@gmail.com

Locations
Greece
University Hospital of Crete, Dep of Medical Oncology Recruiting
Heraklion, Greece
Contact: Dora Hatzidaki    +302810392570    dorachat@med.uoc.gr   
Contact: Ioannis Athanasakis    +302810392783    dclintrials@gmail.com   
Principal Investigator: John Souglakos, MD         
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
  More Information

No publications provided

Responsible Party: Hellenic Oncology Research Group
ClinicalTrials.gov Identifier: NCT01308086     History of Changes
Other Study ID Numbers: CT/09.12
Study First Received: March 1, 2011
Last Updated: June 21, 2014
Health Authority: Greece: National Organization of Medicines

Keywords provided by Hellenic Oncology Research Group:
Cancer
colorectal cancer
adjuvant chemotherapy
capecitabine
oxaliplatin
5 fluorouracil

Additional relevant MeSH terms:
Fluorouracil
Capecitabine
Oxaliplatin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014