Study of Capecitabine In Patients With Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Haematology-Oncology, National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT00697502
First received: June 11, 2008
Last updated: October 31, 2012
Last verified: October 2012
  Purpose

Hypothesis:

Patients with TYMS 2R/2R or 2R/3R appear to be more sensitive to fluoropyrimidines, conferring a higher risk of grade 3-4 fluoropyrimidine related toxicity and a higher response rate compared with 3R/3R. The genotype 3R/3R is more common in East Asia and is associated with greater tolerability to fluoropyrimidine as measured by lower toxicity but also lower response rates. As sensitivity to fluoropyrimidine appears to be affected by TYMS genotype, we hypothesise that patients with TYMS 3R/3R are more tolerant to standard doses of capecitabine and require higher doses to overcome fluoropyrimidine resistance. We designed this study to develop TYMS genotype specific dosing of capecitabine.

Aims:

  1. To determine the maximal tolerated dose (MTD) of capecitabine twice a day for two weeks followed by one week rest period (intermittent schedule) in patients with the advanced/ and or metastatic cancer based on TYMS genotype.
  2. To determine a suitable phase II dose of intermittent schedule capecitabine.
  3. To determine the safety and toxicity of this regimen.
  4. To perform plasma pharmacokinetics of capecitabine.
  5. To determine the relationship between genes of relevance in the fluoropyrimidine pathway with pharmacokinetics and toxicity.

Condition Intervention Phase
Solid Tumors
Drug: Capecitabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Capecitabine In Patients With Solid Tumors

Resource links provided by NLM:


Further study details as provided by National University Hospital, Singapore:

Primary Outcome Measures:
  • To determine the maximal tolerated dose (MTD) of capecitabine twice a day for two weeks followed by one week rest period (intermittent schedule) in patients with the advanced/ and or metastatic cancer based on TYMS genotype. [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Plasma concentrations of capecitabine and its metabolites [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]

    Pharmacokinetic sampling will be performed during cycle 1 on days 1 and 14 at the following time points:

    Baseline (predose), and 15 min, 30 min, 1 hr, 2 hr, 4 hr, 5 hr and 6 hr after dosing. Blood samples will be centrifuged at 1500 g and 4oC for 10 min and supernatant plasma removed and stored below -20oC until analysis. Plasma concentrations of capecitabine and its metabolites will be quantified by a validated liquid chromatography with mass-spectrometry detection (LC-MS-MS) method



Enrollment: 23
Study Start Date: May 2007
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 2: TSER 3R/3R
Cohorts of 3-6 patients in each genotype group will receive escalating doses of capecitabine until MTD is reached. Once MTD is determined, an additional 6-9 patients (for a total of 12 patients) will receive treatment at that dose.
Drug: Capecitabine

Capecitabine (XELODA) is supplied as biconvex, oblong film-coated tablets for oral administration and will be obtained from NUH Cancer Centre pharmacy.

Each light peach-colored tablet contains 150 mg capecitabine and each peach-colored tablet contains 500 mg capecitabine. Capecitabine is to be administered orally within 30 minutes after the end of a meal (breakfast, dinner). Tablets should be swallowed with about 200 mL of water (not fruit juices). Capecitabine will be administered for 14 days followed by a 7 day rest period.

Other Name: XELODA
Experimental: Group 1: TSER 2R/2R or 2R/3R
Cohorts of 3-6 patients in this genotype group will receive escalating doses of capecitabine until MTD is reached. Once MTD is determined, an additional 6-9 patients (for a total of 12 patients) will receive treatment at that dose.
Drug: Capecitabine

Capecitabine (XELODA) is supplied as biconvex, oblong film-coated tablets for oral administration and will be obtained from NUH Cancer Centre pharmacy.

Each light peach-colored tablet contains 150 mg capecitabine and each peach-colored tablet contains 500 mg capecitabine. Capecitabine is to be administered orally within 30 minutes after the end of a meal (breakfast, dinner). Tablets should be swallowed with about 200 mL of water (not fruit juices). Capecitabine will be administered for 14 days followed by a 7 day rest period.

Other Name: XELODA

  Eligibility

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

Inclusion Criteria:

  1. Cytologically or histologically confirmed advanced or metastatic non- hematologic malignancy that had failed previous therapies or cancer for which there are no standard treatment options.
  2. Presence of at least one uni-dimensional measurable lesion as defined by the RECIST criteria.
  3. Required genotype characteristics:

    • Group 1: TSER genotype 2R/2R or 2R/3R
    • Group 2: TSER genotype 3R/3R
  4. Able to swallow capsules
  5. Age>=18 years
  6. Kanorfsky performance status of at least 70% or ECOG performance status <2 (Appendix A)
  7. Life expectancy of at least 3 months
  8. Hb >=9 g/dL
  9. ANC >=1.5 x 10^9/L
  10. Platelet count >=100 x 10^9/L.
  11. Total bilirubin and serum creatinine <=1.5x upper limits of normal reference range (ULN)
  12. Alkaline phosphatase, AST/ALT levels <=2.5x upper limit of normal. If hepatic metastases are present, these parameters could be <=10x the ULN.
  13. Women of reproductive age and men must agree to practice effective contraception during the entire study period. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-child- bearing potential. Females with childbearing potential must have a negative serum pregnancy test within 7days prior to study enrolment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  14. Signed written informed consent

Exclusion Criteria:

  1. Received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic or any investigational therapy within 28 days prior to study drug administration (6 weeks for mitomycin or nitroureas) and not recovered.
  2. Patients who have not recovered from major surgery
  3. Any woman pregnant or lactating.
  4. Known CNS metastases
  5. Renal impairment with a creatinine clearance <=50mL/min (as calculated according to Cockcroft and Gault formula) or serum creatinine > ULN
  6. Clinically significant cardiac disease, eg. Congestive cardiac failure, symptomatic coronary heart disease, cardiac arrhythmia or myocardial infarction within the last 12 months.
  7. Known HIV infection
  8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, other serious uncontrolled concomitant disease, psychiatric illness/ social situation that would limit study compliance.
  9. Known allergies to any component of the study drug
  10. Lack of physical integrity of the upper gastrointestinal tract or those with malabsorption syndrome
  11. Organ allografts
  12. Known dihydropyrimidine dehydrogenase deficiency
  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: NCT00697502

Locations
Singapore
National University Hospital
Singapore, Singapore
Sponsors and Collaborators
National University Hospital, Singapore
Investigators
Principal Investigator: Ross Andrew Soo, MBBS National University Hospital, Singapore
  More Information

Publications:
Responsible Party: Haematology-Oncology, Dr. Ross Soo, National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT00697502     History of Changes
Other Study ID Numbers: PG03/32/06
Study First Received: June 11, 2008
Last Updated: October 31, 2012
Health Authority: Singapore: Domain Specific Review Boards

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

ClinicalTrials.gov processed this record on August 20, 2014