Neoplasms, Obesity
Conditions
Keywords
Capecitabine pharmacokinetics PK, Elevated Body Mass Index (BMI), Advanced Solid Tumors
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.
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.
Interventions
DRUGXeloda
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.
Sponsors
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). \[nonlinear mixed effects modeling approach\] |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Progression Free Survival | Up to 6 months | Progression-free survival will be analyzed using the Kaplan-Meier method. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Xeloda (Capecitabine) |
|---|---|
| Age, Customized 40-49 years | 1 Participants |
| Age, Customized 50-59 years | 2 Participants |
| Age, Customized 60-69 years | 4 Participants |
| Age, Customized 70-79 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
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). \[nonlinear mixed effects modeling approach\]
Time frame: Up to 15 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Xeloda (Capecitabine) | Area Under the Curve (AUC) on Cycle 1 Day 1 and Cycle 1 Day 9 | Cycle 1 Day 1 | 6.84 AUC (ug/ml)*h | Standard Deviation 7.89 |
| Xeloda (Capecitabine) | Area Under the Curve (AUC) on Cycle 1 Day 1 and Cycle 1 Day 9 | Cycle 1 Day 9 | 8.28 AUC (ug/ml)*h | Standard Deviation 6.64 |
Comparison: 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 conductedp-value: 0.4882t-test, 2 sided
Primary
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). \[nonlinear mixed effects modeling approach\]
Time frame: Up to 15 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Xeloda (Capecitabine) | Cmax During Cycle 1 | Cycle 1 Day 1 | 2.44 Cmax (ug/ml) | Standard Deviation 1.89 |
| Xeloda (Capecitabine) | Cmax During Cycle 1 | Cycle 1 Day 9 | 2.71 Cmax (ug/ml) | Standard Deviation 0.98 |
p-value: 0.7497t-test, 2 sided
Secondary
Progression Free Survival
Progression-free survival will be analyzed using the Kaplan-Meier method.
Time frame: Up to 6 months
Population: The median PFS has not been reached (NBR) within the follow-up period of this trial
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Xeloda (Capecitabine) | Progression Free Survival | NA months |
Secondary
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.
Time frame: Up to 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Xeloda (Capecitabine) | Response Rate | 0 percentage |