Capecitabine Pharmacokinetics(PK)-Actual Versus Ideal Body Weight

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by University of Wisconsin, Madison
Sponsor:
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT01828554
First received: April 2, 2013
Last updated: July 16, 2013
Last verified: July 2013
  Purpose

The purpose of this research study is to find what happens to capecitabine in the body when dosed using actual versus ideal body weight in subjects with advanced tumors and elevated body mass index.


Condition Intervention Phase
Advanced Solid Tumors
Obesity
Drug: Xeloda
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Pilot Study Evaluating Pharmacokinetic Parameters of Capecitabine Dosing in Patients With Advanced Cancer and Elevated Body Mass Index

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Comparison of Area Under Curve (AUC) and Cmax between full weight and limited based dosing (non-linear mixed effects modeling approach) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    PK parameters will be summarized it terms of number of observations, means, standard deviations, medians, and ranges, stratified by time point. AUC will be estimated using the Lagrange approximation method and a paired t-test will be used to compare the PK parameters between full weight and limited weight based dosing.


Secondary Outcome Measures:
  • A combination of Response Rate, Evaluation of Measurable Disease, and Progression Free Survival of subjects using Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 (changes in only the largest diameter of the tumor lesions) over time [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Measurable disease is defined as measurable lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques (CT, MRI, x-ray) or as >10 mm with spiral CT scan. All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters). Progression-free survival (PFS) will be defined as time from first dose of capecitabine to time to clinical or imaging evidence of progressive disease.


Estimated Enrollment: 10
Study Start Date: June 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Xeloda (Capecitabine)

Cycle 1: Days 1-7 (21 day cycle): 1250 mg/m2 Xeloda orally twice a day using "Ideal Body Weight" to calculate dosage. Cycle 1, Day 8-No drug.

Cycle 1: Days 9-15 (21 day cycle): 1250 mg/m2 Xeloda orally twice a day using Actual Body Weight to calculate dosage. Days 16-21-No drug.

Cycle 2 and greater: Days 1-14 (21 day cycle): 1250 mg/m2 Xeloda orally twice a day using Actual Body Weight to calculate dosage.

Drug: Xeloda

Cycle 1: Days 1-7 (21 day cycle): 1250 mg/m2 Xeloda orally twice a day using "Ideal Body Weight" to calculate dosage. Cycle 1, Day 8-No drug.

Cycle 1: Days 9-15 (21 day cycle): 1250 mg/m2 Xeloda orally twice a day using Actual Body Weight to calculate dosage. Days 16-21-No drug.

Cycle 2 and greater: Days 1-14 (21 day cycle): 1250 mg/m2 Xeloda orally twice a day using Actual Body Weight to calculate dosage.

Other Name: Capecitabine

  Eligibility

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

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed advanced or metastatic cancer for which capecitabine treatment is considered a standard treatment option.
  • Patients with measurable or evaluable disease are eligible
  • Patient's Body Mass Index must be 30 kg/m2 or higher.
  • Eastern Cooperative Oncology Group performance status 0-2.
  • Age >18 years.
  • Life expectancy of greater than 12 weeks.
  • Patients must have adequate organ and marrow function as defined below:

Hematologic: Absolute Neutrophil Count (ANC) >1000/mcL, Hemoglobin > 8gm/dL (transfusions permitted)and platelets > 75,000/mcL

Renal: serum creatinine ≤ upper limit of normal (ULN) or creatinine clearance (either estimated or calculated) >60 mL/min/1.73 m for patients with creatinine levels above institutional normal.

Females: Crcl =(140-age)(weight in kg)(0.85)/72 x Serum creatinine

Males: Crcl =(140-age)(weight in kg)/72 x Serum creatinine

Hepatic: Serum Bilirubin ≤ 1.5x ULN and No liver metastases: Aspartate aminotransferase(AST)and Alanine transaminase(ALT) ≤ 2.5x ULN Liver metastases: AST and ALT ≤ 5x ULN

  • Ability to understand and the willingness to sign a written informed consent document.
  • Capecitabine is contra-indicated in pregnant women because of known detrimental effects on the fetus. A negative pregnancy test is required in all premenopausal women within 14 days of study therapy initiation. Women of child-bearing potential and men with an active female sexual partner must agree to use adequate contraception (hormonal, surgical, barrier methods or abstinence allowed) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

  • Patients who have had systemic chemotherapies or targeted therapies within 3 weeks or radiotherapy within 2 weeks prior to entering the study or those patients whose adverse events from prior therapies have not recovered to < grade 1 and are still considered clinically significant.
  • Patients receiving any other investigational agents for cancer treatment.
  • Patients with treated, stable brain metastases are allowed to enroll. Patients must be at least 4 weeks from brain radiation and off any medications used to treat brain metastases including steroids. Patients are allowed to be on anti-epileptic medications that are not contraindicated based on the drug-interaction table.
  • Patients with any condition of the gastrointestinal tract that is expected to result in an inability to swallow or absorb oral medications (ie. prior surgical procedures affecting absorption and requiring i.v. alimentation). This will be determined at the discretion of the PI.
  • Patients may not be taking any concomitant drugs that are contraindicated based on the drug-interaction table.
  • Concurrent treatment with warfarin (coumadin) is allowed, but close monitoring of the PT/INR is recommended.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active severe infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant or symptomatic cardiac arrhythmia, other malignancies requiring therapy or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women or women who are breastfeeding are excluded from this study because capecitabine is a pregnancy category D drug and is known to pass to the infant in breastmilk.
  • Patients with known deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to capecitabine.
  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: NCT01828554

Contacts
Contact: Clinical Trials Office Clinical Trials Office (608) 262-5223 cancerconnect@uwcarbone.wisc.edu
Contact: Kari B. Wisinski, M.D. 608- 262- 2876 kbwisinski@medicine.wisc.edu

Locations
United States, Wisconsin
University of Wisconsin-Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53792
Contact: Jennifer Heideman, B.S.N    608-263-6222    Phase1@medicine.wisc.edu   
Sponsors and Collaborators
University of Wisconsin, Madison
Investigators
Principal Investigator: Kari B. Wisinski, M.D. University of Wisconsin, Madison
  More Information

No publications provided

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT01828554     History of Changes
Other Study ID Numbers: OS 12903
Study First Received: April 2, 2013
Last Updated: July 16, 2013
Health Authority: United States: Data and Safety Monitoring Board

Keywords provided by University of Wisconsin, Madison:
Capecitabine pharmacokinetics PK
Elevated Body Mass Index (BMI)
Advanced Solid Tumors

Additional relevant MeSH terms:
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 September 18, 2014