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

• ClinicalTrials.gov Identifier: NCT00353262
• Recruitment Status: Completed
• First Posted: July 18, 2006
• Results First Posted: January 8, 2016
• Last Update Posted: March 4, 2016
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Colorectal Cancer	Drug: Avastin; Drug: Oxaliplatin; Drug: capecitabine [Xeloda]	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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.
• Study Start Date: July 2005
• Actual Primary Completion Date: September 2006
• Actual Study Completion Date: April 2008

Arms and Interventions

Arm	Intervention/treatment
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)

Outcome Measures

Primary Outcome Measures :

1. 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. ]
   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).
2. 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. ]
   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 :

1. 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 ]
   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.
2. 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 ]
   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).
3. 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 ]
   Cmax is defined as maximum observed analyte concentration of capecitabine and its metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
4. 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 ]
   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)
5. 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 ]
   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.
6. 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. ]
   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.
7. 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. ]
   Cmax is defined as maximum observed analyte concentration of Total And Free Platinum.
8. 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 ]
   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.
9. 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 ]
   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.
10. 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 ]
    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).
11. Number Of Participants With Adverse Events (AEs) [ Time Frame: Approximately 3 Years (up to 28 days after the last intake of study medication) ]
    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.
12. Marked Laboratory Abnormalities [ Time Frame: Up to 28 days after last chemotherapy administration ]
    Number of participants with marked laboratory abnormalities (hematology, coagulation, liver function, renal function, protein, electrolytes, miscellaneous).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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
• First Posted: July 18, 2006
• Results First Posted: January 8, 2016
• Last Update Posted: March 4, 2016
• Last Verified: February 2016

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Colonic Diseases; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Capecitabine; Oxaliplatin; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents