Capecitabine Pharmacokinetics(PK)-Actual Versus Ideal Body Weight

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Completed
• CT.gov ID: NCT01828554
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arm: 1
• Duration (Months): 58
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Obesity; Neoplasms	Drug: Xeloda	N/A

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Apr 1, 2018
• Actual Study Completion Date: Apr 1, 2018

Arms and Interventions

Arm

Intervention/Treatment

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 Names: Capecitabine

Outcome Measures

Primary Outcome Measures

1. Area Under the Curve (AUC) on Cycle 1 Day 1 and Cycle 1 Day 9 [Up to 15 days]

   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]

2. Cmax During Cycle 1 [Up to 15 days]

   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]

Secondary Outcome Measures

1. Response Rate [Up to 6 months]

   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.

2. Progression Free Survival [Up to 6 months]

   Progression-free survival will be analyzed using the Kaplan-Meier method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin-Carbone Cancer Center	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• University of Wisconsin, Madison

Investigators

• Principal Investigator: Kari B. Wisinski, M.D., University of Wisconsin, Madison

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 16, 2016

More Information

Additional Information:

• University of Wisconsin Carbone Cancer Center

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT01828554
• Other Study ID Numbers: OS12903; NCI-2013-01267; 2013-0280; A534260; SMPH\MEDICINE\HEM-ONC
• First Posted: Apr 10, 2013
• Last Update Posted: Nov 25, 2019
• Last Verified: Jul 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Wisconsin, Madison: Capecitabine pharmacokinetics PK; Elevated Body Mass Index (BMI); Advanced Solid Tumors
• Additional relevant MeSH terms: Capecitabine

Study Results

Participant Flow

Arm/Group Title	Xeloda (Capecitabine)
Arm/Group Description	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. 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.
Period Title: Overall Study
STARTED	8
COMPLETED	8
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Xeloda (Capecitabine)
Arm/Group Description	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. 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.
Overall Participants	8
Age, Customized (Count of Participants)
40-49 years	1 12.5%
50-59 years	2 25%
60-69 years	4 50%
70-79 years	1 12.5%
Sex: Female, Male (Count of Participants)
Female	4 50%
Male	4 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	8 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 25%
White	6 75%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Curve (AUC) on Cycle 1 Day 1 and Cycle 1 Day 9
Description	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]
Time Frame	Up to 15 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Xeloda (Capecitabine)
Arm/Group Description	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. 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.
Measure Participants	8
Cycle 1 Day 1	6.84 (7.89)
Cycle 1 Day 9	8.28 (6.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Xeloda (Capecitabine)
	Comments	The null hypothesis that the AUC from cycle 1 day 1 (based on ideal body weight) is equal to the AUC from cycle 1 day 9 (based on actual body weight) was tested against the alternative hypothesis that the AUCs are not equal. A linear mixed effect model with patient specific random effects was conducted
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4882
	Comments	A paired t-test will be used to compare the PK parameters between the full weight and limited weight based dosing.
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Cmax During Cycle 1
Description	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]
Time Frame	Up to 15 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Xeloda (Capecitabine)
Arm/Group Description	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. 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.
Measure Participants	8
Cycle 1 Day 1	2.44 (1.89)
Cycle 1 Day 9	2.71 (0.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Xeloda (Capecitabine)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7497
	Comments	A paired t-test will be used to compare the PK parameters between the full weight and limited weight based dosing.
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Response Rate
Description	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.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Xeloda (Capecitabine)
Arm/Group Description	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. 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.
Measure Participants	8
Number (95% Confidence Interval) [percentage]	0

4. Secondary Outcome

Title	Progression Free Survival
Description	Progression-free survival will be analyzed using the Kaplan-Meier method.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

The median PFS has not been reached (NBR) within the follow-up period of this trial

Arm/Group Title	Xeloda (Capecitabine)
Arm/Group Description	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. 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.
Measure Participants	8
Median (95% Confidence Interval) [months]	NA

Adverse Events

Time Frame	up to 9 months
Arm/Group Title	Xeloda (Capecitabine)
Arm/Group Description	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. 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.
All Cause Mortality
	Xeloda (Capecitabine)
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Serious Adverse Events
	Xeloda (Capecitabine)
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	Xeloda (Capecitabine)
	Affected / at Risk (%)	# Events
Total	8/8 (100%)
Blood and lymphatic system disorders
Anemia	1/8 (12.5%)	1
Eye disorders
Eye disorders - Other, specify	1/8 (12.5%)	1
Gastrointestinal disorders
Nausea	6/8 (75%)	15
Constipation	3/8 (37.5%)	3
Diarrhea	3/8 (37.5%)	8
Mucositis oral	3/8 (37.5%)	4
Vomiting	3/8 (37.5%)	5
Abdominal pain	1/8 (12.5%)	2
Stomach pain	1/8 (12.5%)	1
Toothache	1/8 (12.5%)	1
General disorders
Fatigue	4/8 (50%)	4
Pain	2/8 (25%)	3
Edema limbs	1/8 (12.5%)	1
Infections and infestations
Otitis media	1/8 (12.5%)	1
Rhinitis infective	1/8 (12.5%)	1
Sinusitis	1/8 (12.5%)	1
Injury, poisoning and procedural complications
Fall	2/8 (25%)	2
Investigations
INR increased	1/8 (12.5%)	3
Metabolism and nutrition disorders
Anorexia	1/8 (12.5%)	3
Hypoalbuminemia	1/8 (12.5%)	2
Hypokalemia	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/8 (25%)	3
Arthralgia	1/8 (12.5%)	1
Bone pain	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorder - Other, specify	1/8 (12.5%)	1
Pain in extremity	1/8 (12.5%)	2
Nervous system disorders
Dizziness	1/8 (12.5%)	1
Dysgeusia	1/8 (12.5%)	1
Headache	1/8 (12.5%)	1
Peripheral sensory neuropathy	1/8 (12.5%)	1
Renal and urinary disorders
Hematuria	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/8 (25%)	3
Cough	1/8 (12.5%)	2
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome	6/8 (75%)	9
Hyperhidrosis	1/8 (12.5%)	1
Vascular disorders
Thromboembolic event	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.