A Study of Xeloda (Capecitabine) Plus Oxaliplatin in Patients With Colon Cancer - Full Text View

Sponsor:	Hoffmann-La Roche
Information provided by:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT00069121

Purpose

This 2 arm study compared the efficacy and safety of intermittent oral Xeloda plus Eloxatin (oxaliplatin) with that of fluorouracil/leucovorin in patients who have had surgery for colon cancer and no previous chemotherapy. Patients were randomized to receive either 1) XELOX (Xeloda 1000 mg/m^2 Oral twice a day (po bid) in 8 cycles consisting of 2 weeks of treatment followed by 1 week without treatment + 130 mg/m^2 intravenous (iv) oxaliplatin on day 1 of each cycle.) or 2) 5-fluorouracil + leucovorin given by one of two regimens: Leucovorin (LV) 20 mg/m^2 IV bolus injection + 5-FU 425 mg/m^2 IV bolus injection daily on Days 1-5 of a four-week cycle, for a total of six cycles, or LV 500 mg/m^2 by 2-hour IV infusion + 5-FU 500 mg/m^2 IV bolus injection one hour after the start of the LV infusion on day 1 of weeks 1 to 6 of each eight-week cycle, for a total of four cycles. The target sample size is 500+ individuals.

Condition	Intervention	Phase
Colorectal Cancer	Drug: capecitabine [Xeloda] Drug: Leucovorin Drug: 5 FU Drug: Oxaliplatin	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-Label Randomized Phase III Study of Intermittent Oral Capecitabine in Combination With Intravenous Oxaliplatin (Q3W) ("XELOX") Versus Fluorouracil/Leucovorin as Adjuvant Therapy for Patients Who Have Undergone Surgery for Colon Carcinoma American Joint Committee on Cancer / Union Internationale Contre le Cancer (AJCC/UICC) Stage III (Duke Stage C).

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Fluorouracil Leucovorin Citrovorum factor Oxaliplatin Capecitabine Leucovorin Calcium Folinic acid calcium salt pentahydrate

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Disease-free Survival (DFS) [Number of Events] [ Time Frame: Time from randomization date to date of first event/date last known to be event free. Median observation time for DFS was approx 57 mos. ] [ Designated as safety issue: No ]
Number of patients with/without recurrence of the original colon cancer or appearance of a new colon or rectal cancer, or death due to any cause. Based on tumor assessments and survival follow-up assessments.
Disease-free Survival [Time to Event] [ Time Frame: Time from randomization date to date of first event/date last known to be event free. Median observation time for DFS was approx 57 mos. ] [ Designated as safety issue: No ]
Determination of an event was based on tumor assessments and survival follow-up assessments. Any recurrence of the original colon cancer or appearance of a new colon or rectal cancer was to be proven by cytology or histology, when possible. An isolated event of increased CEA, or unexplained clinical deterioration were not considered to be evidence of relapse without support of other objective measurements. The date of relapse was defined as the date of the definitive assessment by objective measurements.

Secondary Outcome Measures:

Relapse-free Survival (RFS) [Number of Events] [ Time Frame: Time from randomization date to date of first event/date last known to be event free. Median observation time for RFS was approx 57 mos. ] [ Designated as safety issue: No ]
Included only recurrence of the original colon cancer, development of a new colon or rectal cancer, and deaths related to any of the following: treatment, recurrence of the original colon cancer, or development of a new colon or rectal cancer.
Relapse-free Survival (RFS) [Time to Event] [ Time Frame: Time from randomization date to date of first event/date last known to be event free. Median observation time for RFS was approx 57 mos. ] [ Designated as safety issue: No ]
Included only recurrence of the original colon cancer, development of a new colon or rectal cancer, and deaths related to any of the following: treatment, recurrence of the original colon cancer, or development of a new colon or rectal cancer. Patients who were not reported as having died at the time of the analysis were censored using the date they were last known to be relapse free.
Overall Survival [Number of Events] [ Time Frame: Time from randomization date to date of death/date last known to be alive. Median observation time for was approx 59 mos. ] [ Designated as safety issue: No ]
Survival was measured as the time from randomization to the date of death, irrespective of the cause of death. Patients who were not reported as having died at the time of the analysis were censored using the date they were last known to be alive.
Overall Survival [Time to Event] [ Time Frame: Time from randomization date to date of death/date last known to be alive. Median observation time for was approx 59 mos. ] [ Designated as safety issue: No ]
Survival was measured as the time from randomization to the date of death, irrespective of the cause of death. Patients who were not reported as having died at the time of the analysis were censored using the date they were last known to be alive.
Number of Participants Assesed for Adverse Events [ Time Frame: followed from Time of Very First Drug Intake and 28 day(s) after Very Last Drug Intake ] [ Designated as safety issue: No ]
Adverse events were presented in individual listings and summarized by Medical Dictionary for Regulatory Activities (MedDRA)System Organ Classes, intensity, and relation to trial treatment. Laboratory data are summarized in two ways: Summary of laboratory abnormalities (regardless of the baseline values), with particular attention to the more clinically relevant Grade 3/4 laboratory abnormalities. Summary of laboratory abnormalities as a shift from baseline.

See Adverse Events module for details.

Enrollment:	1886
Study Start Date:	April 2003
Study Completion Date:	April 2009
Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: XELOX arm Administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of two weeks of treatment followed by one week without treatment) combined with IV oxaliplatin on Day 1 of each cycle. The XELOX combination was administered for a total of eight cycles (24 weeks).	Drug: capecitabine [Xeloda] 1000 mg/m^2 po bid with the first dose given during the evening of Day 1 and last dose given during the morning of Day 15 of each 3-week cycle for a total of eight cycles (24 weeks). Other Names: The XELOX arm: capecitabine administered as an oral twice daily outpatient intermittent treatment (3-week cycles consisting of two weeks of treatment followed by one week without treatment) combined with intravenous (IV) oxaliplatin on Day 1 of each cycle. Capecitabine was administered orally at a dose of 1000 mg/m^2 twice-daily (equivalent to a total daily dose of 2000 mg/m^2) with the first dose given during the evening of Day 1 and last dose given during the morning of Day 15. Oxaliplatin was administered as a 130 mg/m^2 IV infusion over two hours on Day 1 of each cycle. The XELOX combination was administered for a total of eight cycles (24 weeks)
Active Comparator: 5-FU/LV arm Each participating center prespecified which regimen they would use for all patients at that center. Mayo Clinic regimen group: LV 20 mg/m2 IV bolus injection + 5-FU 425 mg/m2 IV bolus injection daily on Days 1-5 of a four-week cycle, for a total of six cycles (24 weeks), or Roswell Park regimen group: LV 500 mg/m2 by two-hour IV infusion + 5-FU 500 mg/m2 IV bolus injection one hour after the start of the LV infusion on Day 1 of Weeks 1 to 6 of each eight-week cycle, for a total of four cycles (32 weeks)	Drug: Leucovorin Mayo Clinic regimen group: 20 mg/m^2 IV bolus injection daily on Days 1-5 of a four-week cycle, for a total of six cycles (24 weeks), or Roswell-Park regimen group: 500 mg/m^2 by two-hour IV infusion on Day 1 of Weeks 1 to 6 of each eight-week cycle, for a total of four cycles (32 weeks) Drug: 5 FU Mayo Clinic regimen group: 425 mg/m^2 IV bolus injection daily on Days 1-5 of a four-week cycle, for a total of six cycles (24 weeks), or Roswell-Park regimen group: 500 mg/m^2 IV bolus injection one hour after the start of the LV infusion on Day 1 of Weeks 1 to 6 of each eight-week cycle, for a total of four cycles (32 weeks) Drug: Oxaliplatin 130 mg/m^2 IV infusion over two hours on Day 1 of each 3-week cycle for a total of eight cycles.

Arms

Assigned Interventions

Experimental: XELOX arm

Administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of two weeks of treatment followed by one week without treatment) combined with IV oxaliplatin on Day 1 of each cycle. The XELOX combination was administered for a total of eight cycles (24 weeks).

Drug: capecitabine [Xeloda]

1000 mg/m^2 po bid with the first dose given during the evening of Day 1 and last dose given during the morning of Day 15 of each 3-week cycle for a total of eight cycles (24 weeks).

Other Names:

The XELOX arm: capecitabine administered as an oral twice daily outpatient intermittent treatment (3-week cycles consisting of
two weeks of treatment followed by one week without treatment) combined with intravenous (IV) oxaliplatin on Day 1 of each
cycle. Capecitabine was administered orally at a dose of 1000 mg/m^2 twice-daily (equivalent to a total daily dose of
2000 mg/m^2) with the first dose given during the evening of Day 1 and last dose given during the morning of Day 15. Oxaliplatin was
administered as a 130 mg/m^2 IV infusion over two hours on Day 1 of each cycle. The XELOX combination was administered for a
total of eight cycles (24 weeks)

Active Comparator: 5-FU/LV arm

Each participating center prespecified which regimen they would use for all patients at that center.

Mayo Clinic regimen group: LV 20 mg/m2 IV bolus injection + 5-FU 425 mg/m2 IV bolus injection daily on Days 1-5 of a four-week cycle, for a total of six cycles (24 weeks), or
Roswell Park regimen group: LV 500 mg/m2 by two-hour IV infusion + 5-FU 500 mg/m2 IV bolus injection one hour after the start of the LV infusion on Day 1 of Weeks 1 to 6 of each eight-week cycle, for a total of four cycles (32 weeks)

Drug: Leucovorin

Mayo Clinic regimen group: 20 mg/m^2 IV bolus injection daily on Days 1-5 of a four-week cycle, for a total of six cycles (24 weeks), or Roswell-Park regimen group: 500 mg/m^2 by two-hour IV infusion on Day 1 of Weeks 1 to 6 of each eight-week cycle, for a total of four cycles (32 weeks)

Drug: 5 FU

Mayo Clinic regimen group: 425 mg/m^2 IV bolus injection daily on Days 1-5 of a four-week cycle, for a total of six cycles (24 weeks), or Roswell-Park regimen group: 500 mg/m^2 IV bolus injection one hour after the start of the LV infusion on Day 1 of Weeks 1 to 6 of each eight-week cycle, for a total of four cycles (32 weeks)

Drug: Oxaliplatin

130 mg/m^2 IV infusion over two hours on Day 1 of each 3-week cycle for a total of eight cycles.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria: Main criteria:

Male and female outpatients ≥ 18 years of age, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1, with histologically confirmed colon carcinoma, Dukes Stage C, who had potentially curative resection of the tumor within eight weeks prior to randomization, with no evidence of remaining tumor. Patients must not have been previously treated by cytotoxic chemotherapy, radiotherapy, or immunotherapy for the currently treated colon cancer.

Exclusion Criteria:

prior treatment with cytotoxic chemotherapy, radiotherapy, or immunotherapy for the currently treated colon cancer.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00069121

Show 259 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:

Clinical Trials

Hoffmann-La Roche

More Information

No publications provided

Responsible Party:	Disclosures Group, Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT00069121 History of Changes
Obsolete Identifiers:	NCT00080691
Other Study ID Numbers:	NO16968
Study First Received:	September 15, 2003
Results First Received:	March 31, 2011
Last Updated:	July 5, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Capecitabine
Oxaliplatin
Leucovorin

Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes

ClinicalTrials.gov processed this record on February 12, 2012