None listed
Conditions
Brief summary
This study involves women receiving chemotherapy for breast cancer. During chemotherapy this study will measure changes in body composition, physical activity levels, changes in the body’s level of inflammation, and changes in the function of liver processes involved in breaking down the chemotherapy. Inflammation is your body’s response to stress or injury. Swelling of an ankle, or a fever, is a common sign of inflammation. People that are obese (body mass index > 30) have been shown to have higher levels of markers of inflammation in their bloodstream. The level of inflammation recorded in blood samples from overweight subjects is still lower than the levels of inflammation experienced in an acute response. However, this type of low level inflammation is sustained over prolonged periods of time and may impact the body’s ability to process medications. Many medications are processed in the body by enzymes in the liver. The chemical messengers in the body that cause inflammation can change the function of these liver enzymes and decrease the ability of the body to process medications. It is not known at this time whether physical activity during chemotherapy affects inflammation or the function of these liver enzymes. This study is seeking to determine if breast cancer patients undergoing chemotherapy have differences in the function of liver enzymes, and if the amount of blood inflammation or physical activity impacts this function.
Interventions
The Inje probe drug cocktail was used in this study to measure in vivo activity of 5 different cytochrome P450 enzymes in all of the recruited study participants, regardless of whether they were non-obese or obese (according to their BMI). Though, the differences in response to Inje probe cocktail will be compared between these two groups. The Inje probe drug cocktail components were: 100 mg caffeine tablet (Key Pharmaceuticals, Pty Ltd, Port Macquarie, NSW, Australia; Batch: P60064); 25 mg losa
The Inje probe drug cocktail was used in this study to measure in vivo activity of 5 different cytochrome P450 enzymes in all of the recruited study participants, regardless of whether they were non-obese or obese (according to their BMI). Though, the differences in response to Inje probe cocktail will be compared between these two groups. The Inje probe drug cocktail components were: 100 mg caffeine tablet (Key Pharmaceuticals, Pty Ltd, Port Macquarie, NSW, Australia; Batch: P60064); 25 mg losartan tablet (Actavis, NJ, USA; Batch: GXM016002); 20 mg omeprazole tablet (Mylan, PA, USA; Batch: ZC16064B); 30 mg of dextromethorphan syrup (Pfizer, Sydney, NSW, Australia; Batch: 17RDX10A); and 1 mg of midazolam syrup (Claris Injectables Ltd, Ahmedabad, India; Batch: B5A0219). The probe drug cocktail will be administered prior to beginning chemotherapy (following diagnosis for neoadjuvant chemotherapy patients, and following diagnosis and surgery for adjuavnt chemotherapy patients) and again following dose 6 of Pacliatxel chemotherapy (of which there are a total of 12 doses given once weekly for 12 weeks). Paclitaxel chemotherapy will be administered immediately after the last cycle of AC chemotherapy (of which there are a total of 4 cycles given every three weeks). Physical activity levels (daily step counts) will be assessed in the participants for 3 weeks (21 days) following cycle one of AC chemotherapy, for 1 week (7 days) following dose one of Paclitaxel, and for 1 week (7 days) following dose six of Paclitaxel. The average daily step counts will be passively assessed using FitBit One devices; this is not an exercise intervention as patients are not required to perform any physical activity, other than what they choose to do themselves. FitBit devices will be given to patients prior to each of the three measuring periods (described above here) and collected at the end of each of measuring period for data upload and charging.
Sponsors
Canterbury District Health Board Research Office
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Women of age 18 or older. • Obese (BMI greater than or equal to 30 kg/m2) or normal weight (BMI ranging from 18.5-24.9 kg/m2) at diagnosis, according to BMI scoring. • Ability to understand and give written informed consent. • Ability to take oral medications. • Clinically defined stage II or III breast cancer. • Planned neoadjuvant or adjuvant chemotherapy with AC-T (cyclophosphamide, doxorubicin, paclitaxel). • Willing to wear FitBit One® throughout the selected cycles/doses of chemotherapy. • Willing to take probe drug cocktail and provide subsequent blood/urine samples. • No known sensitivity or contraindications to any of the cocktail components, including: midazolam, losartan, caffeine, omeprazole and dextromethorphan. • Have adequate end-organ function, as measured by: Creatinine less than or equal to 2x Upper Limit of Normal (ULN) Haemoglobin greater than 90 g/L Systolic Blood Pressure greater than 90 mmHg AST less than or equal to 3x ULN ALT less than or equal to 3x ULN Bilirubin less than or equal to 2x ULN
Exclusion criteria
• Enrollment in any conflicting clinical trials. • Uncontrolled intercurrent illness including, but not limited to, on-going or active infection and psychiatric illness/social situations that would limit compliance with study requirements. • Patients that suffer from ongoing urinary incontinence and/or current use of a urinary catheter. • Cirrhosis as documented by liver biopsy, fibroscan, or a clinical history laboratory findings consistent with cirrhosis. • Impaired mobility due to disability or medical illness. For example: o Amputation of either or both lower extremities o Restricted to a wheelchair • Are known to have active infection with a viral hepatitis (e.g. Hepatitis B or C). • Unwilling to comply with requirements for recording times when the FitBit One® is not worn. • Any abnormal laboratory value or medical condition that would, in the investigators’ judgement, make the patient a poor candidate for the study. • Use of concurrent medications known to be inhibitors or inducers of the cytochrome P450 enzymes being studied. Weak inducers or inhibitors will be acceptable for inclusion.
Outcome results
None listed