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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00353262
First received: July 17, 2006
Last updated: February 4, 2016
Last verified: February 2016
  Purpose
This single arm study will investigate possible pharmacokinetic interactions between Xeloda and oxaliplatin, and assess whether the pharmacokinetics of Xeloda and/or oxaliplatin is influenced by the addition of Avastin. All subjects will provide samples for pharmacokinetic analysis during the first 3 cycles of treatment. In cycles 1 and 2 patients will receive a treatment regimen containing Xeloda (1000mg/m2 bid) and oxaliplatin (130mg/m2 iv) and in cycle 3 Avastin (7.5mg/kg iv) will be added to the regimen. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Condition Intervention Phase
Colorectal Cancer
Drug: Avastin
Drug: Oxaliplatin
Drug: capecitabine [Xeloda]
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Study to Assess the Pharmacokinetic Interaction Between Xeloda and Oxaliplatin in Patients With Metastatic Colorectal Cancer.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Area Under The Plasma Concentration-Time Curve From Zero To Infinity (AUC0-Inf) of 5'-Deoxy-5-fluorouridine 5'-(DFUR) [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose. ] [ Designated as safety issue: No ]
    AUC0-infinity represents the area under the concentration-time curve of the analyte (5'-DFUR) in plasma over the time interval from 0 extrapolated to infinity. The analyte 5'-DFUR, the direct precursor of 5-fluorouracil (5-FU), is considered to be the most important metabolite of capecitabine in plasma. The unit of measure was nanograms per millilitre per hour (ng/mL * hr).

  • AUC0-inf for Free Platinum [ Time Frame: Predose , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the 2 hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3. ] [ Designated as safety issue: No ]
    AUC0-infinity represents the area under the concentration-time curve of the analyte (free platinum) in plasma over the time interval from 0 extrapolated to infinity. AUC0-inf for free platinum was calculated for each participant from the concentration-data obtained on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3. Free platinum is not bound to plasma proteins and is considered to be the most clinically significant measure of pharmacological and toxicological activity.


Secondary Outcome Measures:
  • AUC (0-infinity) of Capecitabine and Its Metabolites (5'-DFCR, 5-FU, and FBAL) [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose ] [ Designated as safety issue: No ]
    AUC0-infinity represents the area under the concentration-time curve of the analytes (5'-DFCR, 5-FU, and FBAL) in plasma over the time interval from 0 extrapolated to infinity. After oral administration, capecitabine is first metabolized in the liver to 5'-deoxy-5-fluorocytidine (5'-DFCR), which is then converted to 5'-DFUR, and then catalytically activated to 5-FU.

  • AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL) [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve from time zero to the time of the last measurable plasma concentration time point of capecitabine and its metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL).

  • Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL) [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose ] [ Designated as safety issue: No ]
    Cmax is defined as maximum observed analyte concentration of capecitabine and its metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)

  • Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL) [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose ] [ Designated as safety issue: No ]
    t1/2 Beta is the time measured for the plasma concentration to decrease by 1 half to its original concentration of capecitabine and its metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)

  • AUC0-infinity for Total Platinum [ Time Frame: Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3 ] [ Designated as safety issue: No ]
    AUC0-infinity represents the area under the concentration-time curve of the analyte (total platinum) in plasma over the time interval from 0 extrapolated to infinity.

  • AUC0-last of Total And Free Platinum [ Time Frame: pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3. ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve from time zero to the time of the last measurable plasma concentration time point of Total And Free Platinum.

  • Cmax of Total And Free Platinum [ Time Frame: Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3. ] [ Designated as safety issue: No ]
    Cmax is defined as maximum observed analyte concentration of Total And Free Platinum.

  • T1/2 Beta of Total And Free Platinum [ Time Frame: Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3 ] [ Designated as safety issue: No ]
    T1/2 beta is the time measured for the plasma concentration to decrease by 1 half to its original concentration of total and free platinum.

  • Volume of Distribution at Steady State (VSS) of Total And Free Platinum [ Time Frame: Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours ] [ Designated as safety issue: No ]
    VSS is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.

  • Clearance of Total And Free Platinum [ Time Frame: Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3 ] [ Designated as safety issue: No ]
    CL is a calculation of the rate at which a drug is removed from the body via renal, hepatic and other clearance pathways, expressed as volume (milliliters) per unit of time (hour).

  • Number Of Participants With Adverse Events (AEs) [ Time Frame: Approximately 3 Years (up to 28 days after the last intake of study medication) ] [ Designated as safety issue: No ]
    An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product. This includes any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Pre-existing conditions which worsened during the study were also to be reported as AEs.

  • Marked Laboratory Abnormalities [ Time Frame: Up to 28 days after last chemotherapy administration ] [ Designated as safety issue: No ]
    Number of participants with marked laboratory abnormalities (hematology, coagulation, liver function, renal function, protein, electrolytes, miscellaneous).


Enrollment: 36
Study Start Date: July 2005
Study Completion Date: April 2008
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Avastin
7.5mg/kg iv (cycle 3 only)
Drug: Oxaliplatin
130mg/m2 iv (cycles 1, 2 and 3)
Drug: capecitabine [Xeloda]
1000mg/m2 po bid (cycles 1, 2 and 3)

  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;
  • adenocarcinoma of colon or rectum, with metastatic or locally advanced disease.

Exclusion Criteria:

  • previous systemic treatment for advanced or metastatic disease;
  • previous treatment with oxaliplatin or Avastin.
  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: NCT00353262

Locations
Canada, Ontario
Hamilton, Ontario, Canada, L8V 5C2
Ottawa, Ontario, Canada, K1H 8L6
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00353262     History of Changes
Other Study ID Numbers: NP18587 
Study First Received: July 17, 2006
Results First Received: December 4, 2015
Last Updated: February 4, 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
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 28, 2016