Capecitabine Pharmacokinetics(PK)-Actual Versus Ideal Body Weight

Study Overview
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Brief Summary
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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.

Detailed Description
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Cycle 1 : Capecitabine 1,250 mg/m2 orally Per os (PO) once a day (BID) for 7 consecutive days (D1 - D7) will be administered by subject (with Ideal Body Weight being used to determine BSA) for dosage. Day 8-No drug administered. Capecitabine 1,250 mg/m2 PO BID for 7 more consecutive days (D9 - D15) will be administered by subject (with Actual Body Weight being used to determine BSA) for dosage. There will be 6 consecutive days that no drug will be administered by subject (Days 16-21). Cycle 2 and beyond: Capecitabine 1,250 mg/m2 PO BID for 14 consecutive days (D1 - D14) will be administered by subject (with Actual Body Weight being used to determine BSA) for dosage. Days 15-21-No drug administered.

Official Title
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Pilot Study Evaluating Pharmacokinetic Parameters of Capecitabine Dosing in Patients With Advanced Cancer and Elevated Body Mass Index

Conditions
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Obesity, Neoplasms

Intervention / Treatment
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* Drug: Xeloda


Participation Criteria
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Eligibility Criteria
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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 (microliters), Hemoglobin > 8gm/dL (transfusions permitted) and platelets > 75,000/mcL Renal: serum creatinine ≤ upper limit of normal (ULN) or creatinine clearance (CrCl) (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 Prothrombin Time/International Normalized Ratio (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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xeloda (Capecitabine)<br>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<br>* 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.<br>* Other names: Capecitabine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve (AUC) on Cycle 1 Day 1 and Cycle 1 Day 9 | AUC will be calculated for Capecitabine dosed for Ideal Body Weight during the first cycle (days 1-7) and for Capecitabine dosed for Actual Body Weight for first cycle (days 9-15). [nonlinear mixed effects modeling approach] | Up to 15 days | 
| Cmax During Cycle 1 | Cmax will be reported for Capecitabine dosed for Ideal Body Weight during the first cycle (days 1-7) and for Capecitabine dosed for Actual Body Weight for first cycle (days 9-15). [nonlinear mixed effects modeling approach] | Up to 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Responses will be determined using RECIST v. 1.1 criteria and summarized in tabular format. The complete and partial response rates will be calculated and reported along with the corresponding 95% confidence intervals. | Up to 6 months | 
| Progression Free Survival | Progression-free survival will be analyzed using the Kaplan-Meier method. | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Capecitabine pharmacokinetics PK, Elevated Body Mass Index (BMI), Advanced Solid Tumors