Effect of Weight on the Population Pharmacokinetic Analysis of Doxorubicin and Cyclophosphamide

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Weight on the Population Pharmacokinetic Analysis of Doxorubicin and Cyclophosphamide

Conditions
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Breast Cancer, Obesity

Intervention / Treatment
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* Drug: Doxorubicin
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Doxorubicin and cyclophosphamide<br> | Drug: Doxorubicin<br>* Dosed by the patient's treating physician according to local standard of care.<br>Drug: Cyclophosphamide<br>* dosage form: IV, Dosage, frequency, and duration: According to local standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance (Cl) for Doxorubicin and Cyclophosphamide | Cyclophosphamide analysis was not possible due to rapid drug degradation | 0-48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Pharmacokinetics, Obesity, Doxorubicin, Cyclophosphamide, Weight