Clinical trial NCT01537029: Effect of Weight on the Population Pharmacokinetic Analysis of Doxorubicin and Cyclophosphamide
Official title: Effect of Weight on the Population Pharmacokinetic Analysis of Doxorubicin and Cyclophosphamide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Breast Cancer
Obesity
Keywords: Breast cancer
Pharmacokinetics
Obesity
Doxorubicin
Cyclophosphamide
Weight
Lead sponsor: Texas Tech University Health Sciences Center
Sponsor class: OTHER
Collaborators: name: University of Texas
First posted: 2012-02-22
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: To determine the effect of weight on doxorubicin and cyclophosphamide plasma clearance in participants who are normal weight (body mass index \[BMI\] \< 25 kg/m2, overweight or class I obese (BMI 25-34.9 kg/m2), or class II-III obese (BMI ≥ 35 kg/m2). The hypothesis is that participants who weigh more will have higher doxorubicin and cyclophosphamide clearances than participants who weigh less. Restated, the area under the drug-concentration time profile, also known as the AUC, in participants will decrease as participant weight increases.

Detailed description: This single site study will be conducted at the UT Southwestern Simmons Cancer Center. This study is designed to measure drug concentrations in the blood of 18 female breast cancer patients who require doxorubicin (30 minute infusion) and cylcophosphamide (30 minute infusion) as part of standard medical care. Up to a total of 40 adult female participants will be consented for the study at the cancer center. Eighteen of these participants are needed to complete the study. The others will likely be screen failures. The participants will have no more than 100 ml of blood drawn via a peripheral intravenous catheter just prior to the doxorubicin infusion, and then at 0.5, 1, 1.5, 2, 3, 4, 5, 12-24, and 24-72 h after the beginning of the doxorubicin infusion. The 5 hour blood draw is optional. The intravenous catheter will be removed when the participant is discharged from the cancer center on day 1. The participant will be asked to return to the cancer center at 12-24 and 24-72 hours to have the final 2 blood draws conducted.

The participants must be treated with Doxurubicin and Cyclophosphamide in order to participate in this pharmacokinetic analysis study.

Eligibility criteria: Inclusion Criteria:

* Females, age 18 years of age or older, of all racial and ethnic origins that are scheduled to receive the first cycle of a single intravenous dose of doxorubicin (30 minute infusion) and cylcophosphamide (30 minute infusion) as part of standard medical care for breast cancer. English and/or Spanish speaking participants are eligible to participate.

Exclusion Criteria:

* Pregnant or nursing or unwilling to use a reliable contraception method during the study. The effects of doxorubicin and cyclophosphamide on pregnancy are unknown. In addition, the metabolic changes that accompany pregnancy may alter the concentration-time profile of doxorubicin or cyclophosphamide, so that the pregnancy and post-partum state would be a confounding variable.
* Participants unwilling to comply with study procedures.
* CrCl \< 10 ml/min
* Participants requiring peritoneal or hemodialysis
* Serum bilirubin \> 1.19 mg/dL
* Receipt of the following drugs that: a) Alter doxorubicin concentrations: carbamazepine, cyclosporine, fosphenytoin, paclitaxel, phenytoin, sorafenib, valspodar, verapamil; b) Alter cyclophosphamide concentrations: cyclosporine, nevirapine, ondansetron; c) All other drugs will be reviewed during screening of the patient

Primary outcomes:
measure: Clearance (Cl) for Doxorubicin and Cyclophosphamide
timeFrame: 0-48 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
Study officials:
affiliation: Texas Tech University HSC
name: Ronald G Hall, PharmD
role: PRINCIPAL_INVESTIGATOR
References: