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A Study of Xeloda (Capecitabine) in Patients With Metastatic Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00069108
First received: September 15, 2003
Last updated: March 3, 2016
Last verified: March 2016
  Purpose
This 2 arm study will assess the efficacy and safety of intermittent oral Xeloda, or iv fluorouracil/leucovorin, in combination with intravenous Eloxatin (oxaliplatin) in patients previously treated for metastatic colorectal cancer. Patients will be randomized to receive either 1)XELOX (Xeloda 1000mg/m2 po bid on days 1-15 + oxaliplatin) in 3 week cycles or 2) FOLFOX-4 (oxaliplatin + leucovorin + 5-FU in 2 week cycles. The anticipated time on study treatment is until disease progression, and the target sample size is 500+ individuals.

Condition Intervention Phase
Colorectal Cancer
Drug: 5 FU
Drug: Leucovorin
Drug: Oxaliplatin
Drug: capecitabine [Xeloda]
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: An Open-Label Randomized Phase III Study of Intermittent Oral Capecitabine in Combination With Intravenous Oxaliplatin (Q3W) ("XELOX") Versus Bolus and Continuous Infusion Fluorouracil/ Intravenous Leucovorin With Intravenous Oxaliplatin (Q2W) ("FOLFOX4") as Treatment for Patients With Metastatic Colorectal Cancer Who Have Received Prior Treatment With CPT-11 in Combination With 5-FU/LV as First Line Therapy

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Progression free survival (PFS) is defined as the time from the date of randomization to the day of documented disease progression or death from any cause. It was based on tumor assessments made according to the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0, wherein progressive disease (PD) was defined as at least a 20% increase in the sum of the longest diameter (LD) of the target lesions (TLs), taking as reference the smallest sum LD recorded since the treatment started or appearance of one or more new lesions or unequivocal progression of existing non-target lesions. Participants with neither disease progression nor death were censored at the last date of the last tumor assessment confirming that they had not progressed. Participants with no tumor assessments after baseline but who were still alive at the time of the clinical cut-off were censored at date of randomization


Secondary Outcome Measures:
  • Progression Free Survival Based on Independent Review Committee Assessment [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Progression free survival (PFS) is defined as the time from the date of randomization to the day of documented disease progression or death from any cause. It was based on tumor assessments made according to the RECIST version 1.0, wherein PD was defined as at least a 20% increase in the sum of the LD of the TLs, taking as reference the smallest sum LD recorded since the treatment started or appearance of one or more new lesions or unequivocal progression of existing non-TLs. Participants with neither disease progression nor death were censored at the last date of the last tumor assessment confirming that they had not progressed. Participants with no tumor assessments after baseline but who were still alive at the time of the clinical cut-off were censored at date of randomization. This PFS evaluation was based on Independent Review Committee Assessment.

  • Progression Free Survival Based on Treatment Analysis- Intent To Treat Population [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Progression free survival (PFS) is defined as the time from date of randomization to day of documented disease progression or death from any cause. It was based on tumor assessments made according to the RECIST version 1.0, wherein PD was defined as at least a 20% increase in the sum of LD of the TLs, taking as reference the smallest sum LD recorded since the treatment started or appearance of one or more new lesions or unequivocal progression of existing non-TLs. Participants with neither disease progression nor death were censored at the last date of the last tumor assessment confirming that they had not progressed. Participants with no tumor assessments after baseline but who were still alive at the time of the clinical cut-off were censored at date of randomization. PFS was analyzed using an on-treatment approach included only disease progression and death that occurred no later than 28 days after the last confirmed intake of study medication in the primary study treatment phase.

  • Progression Free Survival Based on Treatment Analysis- Per Population [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Progression free survival (PFS) is defined as the time from the date of randomization to the day of documented disease progression or death from any cause. It was based on tumor assessments made according to the RECIST version 1.0, wherein PD was defined as at least a 20% increase in the sum of the LD of the TLs, taking as reference the smallest sum LD recorded since the treatment started or appearance of one or more new lesions or unequivocal progression of existing non-TLs. Participants with neither disease progression nor death were censored at the last date of the last tumor assessment confirming that they had not progressed. Participants with no tumor assessments after baseline but who were still alive at the time of the clinical cut-off were censored at date of randomization

  • Best Overall Response, Investigators' Assessments [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Best overall response is best response recorded from start of treatment until disease progression/recurrence where responses include complete response (CR), partial response (PR), or stable disease (SD). CR was defined as disappearance of all TLs, non-TLs along with normalization of tumor marker level. PR is at least 30% decrease in sum of the LD of TLs, taking as reference baseline sum LD. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking reference of smallest sum LD since treatment started. It was dependent on achievement of measurement and confirmation criteria. BOR .i.e. CR or PR was confirmed by repeat assessments performed within 4 weeks. For SD, follow-up assessments had to meet the SD criteria at least once after study entry within 6 to 8 weeks.

  • Best Overall Response, Independent Review Committee Assessment [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Best overall response is best response recorded from start of treatment until disease progression/recurrence where responses include CR, PR, or SD. CR was defined as disappearance of all TLs, non-TLs along with normalization of tumor marker level. PR is at least 30% decrease in sum of the LD of TLs, taking as reference baseline sum LD. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking reference of smallest sum LD since treatment started. It was dependent on achievement of measurement and confirmation criteria. BOR .i.e. CR or PR was confirmed by repeat assessments performed within 4 weeks, for SD, follow-up assessments had to meet the SD criteria at least once after study entry within 6 to 8 weeks. This PFS evaluation was based on Independent Review Committee Assessment.

  • Overall Survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Overall survival was measured as the time from the date of randomization to the date of death. Participant who were not reported to have died at the time of the analysis were censored using the date they were last known to be alive.

  • Time To Response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Time to response (TOR) (best response of CR or PR) was measured as the time from randomization to the first date on which the measurement criteria for CR or PR (whichever status was recorded first) were met. CR for TLs was defined as disappearance of all TLs and for non-TLs as disappearance of all non-TLs and normalization of tumor marker level. PR was defined as at least 30% decrease in the sum of the LD of TLs, taking as reference the baseline sum LD.

  • Duration Of Response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Duration of response (DOR) is defined as the time when CR or PR was first met up to first date that PD or death is documented. CR is defined as disappearance of all TLs and non TLs, PR is defined as at least 30% decrease in the sum of the LD of TLs, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the sum of the LD of the TLs, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions for the TLs or the appearance of one or more new lesions and/or unequivocal progression of existing non-TLs.

  • Time To Treatment Failure [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Time to treatment failure was defined as the time from the date of randomization to the first occurrence of adverse event (AE), insufficient therapeutic response, death, failure to return, or refusing treatment/being uncooperative/withdrawing consent.

  • Number of Participants With Marked Post-baseline Laboratory Abnormalities by Trial Treatment [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Laboratory abnormalities were defined as those values that were outside the Roche defined reference range and showed a clinically relevant change from baseline. All laboratory parameters were categorized according to the National Cancer Center Common Toxicity Criteria (NCI-CTCAE) grading system. Incidence of Grade 1 to 4 laboratory abnormalities are presented in the table below.


Enrollment: 627
Study Start Date: July 2003
Study Completion Date: August 2006
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: XELOX
Participants received XELOX (oxaliplatin and capecitabine). Oxaliplatin was administered 130 mg/m^2 intravenous (IV) infusion over 2 hours (every 3 weeks [Day 1]) before the first dose of capecitabine. Capecitabine was administered orally within 30 minutes after the end of a meal (breakfast and dinner) at a dose of 1000 mg/m^2 twice-daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of Day 1 and last dose the morning of Day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) for up to 8 cycles (24-weeks).
Drug: Oxaliplatin
As prescribed, in 3 week cycles
Drug: capecitabine [Xeloda]
1000mg/m2 po bid on days 1-15 of each 3 week cycle
Active Comparator: FOLFOX-4
Participants received FOLFOX-4 (combination of oxaliplatin, leucovorin [LV] and 5-fluorouracil [5-FU] combination). Oxaliplatin was administered as an 85 mg/m^2 IV infusion over 2 hours (on Day 1 only); with LV infusion as 200mg/m^2 over 2 hours followed by 5-FU, given as 400mg/m^2 bolus injection over 2-4 minutes, and then as a 600 mg/m^2 continuous infusion over 22 hours. On Day 2, Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection over 2-4 minutes, and 5-FU 600 mg/m^2 continuous infusion was repeated over 22 hours. It was (2-week cycles comprising 48 hours of infusion and 12 days of rest) for up to 12 cycles (24- weeks).
Drug: 5 FU
As prescribed, in 2 week cycles
Drug: Leucovorin
As prescribed, in 2 week cycles
Drug: Oxaliplatin
As prescribed, in 2 week cycles

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients >=18 years of age;
  • metastatic colorectal cancer;
  • >=1 target lesion;
  • failed first-line chemotherapy with 5-fluorouracil and irinotecan.

Exclusion Criteria:

  • previous treatment with oxaliplatin;
  • progressive or recurrent disease during or within 6 months of completion of first-line chemotherapy;
  • >=1 previous chemotherapeutic agent or systemic anticancer regimen for metastatic disease.
  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: NCT00069108

  Show 87 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00069108     History of Changes
Other Study ID Numbers: NO16967 
Study First Received: September 15, 2003
Results First Received: January 27, 2016
Last Updated: March 3, 2016
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
Capecitabine
Fluorouracil
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 05, 2016