Investigating Paclitaxel Toxicity in Breast Cancer: The Roles of Physical Activity and Body Composition.

Breast Cancer Clinical Trial

— PABTOX  

Official title:

Dose-limiting Toxicities of Paclitaxel in Breast Cancer Patients: Studying Interactions Between Pharmacokinetics, Physical Activity, and Body Composition: an Observational Pilot Study.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06387901
• Other study ID #: PABTOX - part 1
• Status: Not yet recruiting
• Start date: May 6, 2024
• Est. completion date: October 31, 2025

Study information

• Verified date: March 2024
• Source: Universitair Ziekenhuis Brussel
• Contact: Len De Nys
• Phone: +32 472 99 49 48
• Email: Len.de.nys[@]vub.be
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study looks into how a common breast cancer treatment, paclitaxel, can sometimes cause severe side effects that make it hard for patients to continue treatment. These side effects can significantly affect a patient's quality of life and even impact their recovery and overall health costs. What's interesting about this research is that it considers how a patient's lifestyle, specifically their physical activity levels and body makeup (like how much muscle and fat they have), might influence these side effects.

The researchers are doing a detailed study with 40 women receiving paclitaxel treatment, tracking how the drug is processed in their bodies and how their body composition and physical activity might play a role in the side effects they experience. They are using a special method to monitor drug levels in the blood and are also keeping tabs on the patients' health and physical activity through questionnaires and modern tracking devices.

The goal here is twofold: first, to better understand why these side effects happen to some people and not others, and second, to develop a model that can predict who might be at higher risk for these side effects based on their body composition, lifestyle, and how their body handles the drug. This could lead to more personalized treatment plans that could help reduce the risk of severe side effects and improve the overall treatment experience for patients with breast cancer.

In simpler terms, this research is trying to find a way to make breast cancer treatment with paclitaxel safer and more comfortable by considering how a person's lifestyle and body type might affect their reaction to the drug. This could make a big difference in helping patients complete their treatment successfully and with a better quality of life.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: October 31, 2025
• Est. primary completion date: May 6, 2025
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Female patients with a diagnosis of breast cancer: Specifically targeting those diagnosed with stage II or III breast cancer, to understand the effects of paclitaxel within a somewhat uniform disease severity group.

• Planned for 12 cycles of Paclitaxel (PTX) in a (neo-)adjuvant setting: The study focuses on patients scheduled to undergo a standard 12-week, once-a-week paclitaxel chemotherapy regimen as part of their treatment plan.

• Age 18 or older in (pre-)menopausal status: Adult patients of any menopausal status are eligible, ensuring a wide demographic representation.

• Prior taxane use is allowed if treatment in the adjuvant setting finished over a year ago: This criterion allows for the inclusion of patients who may have previously undergone taxane-based treatments, provided there has been a sufficient washout period to minimize the influence of prior treatments on the study outcomes.

Exclusion Criteria

• Cognitive impairment (unable to understand test instructions): Ensuring participants can comprehend and follow study procedures and requirements is crucial for data integrity and participant safety.

• Participation in clinical trials of experimental drugs: To avoid confounding effects from other investigational treatments and focus on the impact of standard-of-care paclitaxel therapy.

• Documented intolerance or allergy to PTX (non-documented intolerance or allergy will lead to drop-out): Participants must be able to tolerate paclitaxel, as adverse reactions could compromise their safety and affect study results.

Interacting drugs in home medication: Patients using medications known to interact with paclitaxel could experience altered drug metabolism or increased toxicity, potentially skewing study outcomes.

• Male sex: The study is focused on breast cancer in female patients, as the disease's presentation, treatment, and outcomes can vary significantly between genders.

• Age under 18 years: Ensuring all participants are legal adults helps adhere to ethical standards and regulatory requirements concerning consent and participation in clinical research.

Related Conditions & MeSH terms

• Body Weight
• Breast Cancer
• Breast Neoplasms
• Chemotherapeutic Agent Toxicity
• Chemotherapeutic Toxicity
• Paclitaxel Adverse Reaction
• Physical Inactivity

Intervention

Drug:
• Paclitaxel Chemotherapy
Participants will receive paclitaxel, a taxane chemotherapeutic agent used in the treatment of breast cancer. The administration involves an intravenous infusion of paclitaxel at a dosage of 80 mg/m². The treatment is scheduled once a week, continuing for a total duration of 12 weeks. This regimen is part of a (neo-)adjuvant therapy for female patients diagnosed with stage II or III breast cancer. The intervention aims to assess the pharmacokinetics of paclitaxel in relation to patient body composition and physical activity, evaluating its impact on dose-limiting toxicities and overall treatment efficacy.

Locations

Country	Name	City	State
Belgium	Vrije Universiteit Brussel	Brussel	Jette

Sponsors (3)

Lead Sponsor	Collaborator
Universitair Ziekenhuis Brussel	University Ghent, Vrije Universiteit Brussel

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Treatment-Related Adverse Events	Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0	During the whole treatment (12 cycles, each cycle is 7 days) and 7 days post-treatment.
Other	Body Composition Measurement via Bioelectrical Impedance Analysis (BIA) (muscle mass)	This outcome measure involves assessing muscle mass (kg), using Bioelectrical Impedance Analysis (BIA). The aim is to determine the impact of body composition on pharmacokinetics and the occurrence of dose-limiting toxicities (DLTs) in breast cancer patients undergoing paclitaxel treatment.	BIA assessments are scheduled at baseline (prior to the start of paclitaxel treatment), cycle 6 (week 6), and cycle 12 (week 12). Each cycle is 7 days.
Other	Body Composition Measurement via Bioelectrical Impedance Analysis (BIA) (fat %)	This outcome measure involves assessing fat %, using Bioelectrical Impedance Analysis (BIA). The aim is to determine the impact of body composition on pharmacokinetics and the occurrence of dose-limiting toxicities (DLTs) in breast cancer patients undergoing paclitaxel treatment.	BIA assessments are scheduled at baseline (prior to the start of paclitaxel treatment), cycle 6 (week 6), and cycle 12 (week 12). Each cycle is 7 days.
Other	Body Composition Measurement via Dual X-ray Absorptiometry (DEXA) (muscle mass)	This outcome measure involves the use of Dual X-ray Absorptiometry (DEXA) to assess skeletal muscle mass (kg) in the whole body and segmented regions. This analysis aims to explore the relationship between body composition and the pharmacodynamics of paclitaxel, focusing on its efficacy and toxicity.	DEXA scans are conducted at baseline (prior to the start of paclitaxel treatment), cycle 6 (week 6), and cycle 12 (week 12). Each cycle is 7 days.
Other	Body Composition Measurement via Dual X-ray Absorptiometry (DEXA) (fat mass)	This outcome measure involves the use of Dual X-ray Absorptiometry (DEXA) to assess fat mass (kg) in the whole body and segmented regions. This analysis aims to explore the relationship between body composition and the pharmacodynamics of paclitaxel, focusing on its efficacy and toxicity.	DEXA scans are conducted at baseline (prior to the start of paclitaxel treatment), cycle 6 (week 6), and cycle 12 (week 12). Each cycle is 7 days.
Other	Body Composition Measurement via Dual X-ray Absorptiometry (DEXA) (extracellular fluid)	This outcome measure involves the use of Dual X-ray Absorptiometry (DEXA) to assess extracellular fluid (L), in the whole body and segmented regions. This analysis aims to explore the relationship between body composition and the pharmacodynamics of paclitaxel, focusing on its efficacy and toxicity.	DEXA scans are conducted at baseline (prior to the start of paclitaxel treatment), cycle 6 (week 6), and cycle 12 (week 12). Each cycle is 7 days.
Other	The European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30)	The EORTC QLQ-C30 is a well-established instrument designed to assess the quality of life in cancer patients. It covers various dimensions including physical, emotional, and social functioning, as well as symptoms related to cancer and its treatment. This questionnaire aims to evaluate how paclitaxel treatment impacts the overall well-being and daily functioning of breast cancer patients.	Administered at baseline (prior to the start of paclitaxel treatment), and after cycles 6 (week 6), 9 (week 9), and 12 (week 12). Each cycle is 7 days.
Other	EORTC QLQ-BR45 Breast (BR) Cancer Module	This questionnaire is an add-on module to the QLQ-C30 for patients with breast cancer. It assesses symptoms and side effects specific to breast cancer and its treatment, body image, sexual functioning, and future perspective. The aim is to capture the specific quality of life concerns of breast cancer patients undergoing paclitaxel treatment.	Completed alongside the QLQ-C30 at baseline, and following cycles 6, 9, and 12. Each cycle is 7 days.
Other	EORTC QLQ- Chemotherapy-Induced Peripheral Neuropathy (CIPN) 20	The QLQ-CIPN20 is designed to assess symptoms of chemotherapy-induced peripheral neuropathy, a common side effect of paclitaxel. It evaluates sensory, motor, and autonomic symptoms related to neuropathy. This questionnaire will help quantify the extent of neuropathic side effects experienced by the patients and their impact on daily activities and quality of life.	This questionnaire is administered at baseline, and following cycles 6, 9, and 12. Each cycle is 7 days.
Other	European Health Interview Survey Physical Activity Questionnaire (EHIS PAQ)	The EHIS PAQ is designed to gather comprehensive data on physical activity levels in various domains, including work, leisure time, and daily activities. This tool will assess changes in physical activity patterns among breast cancer patients receiving paclitaxel and explore correlations with treatment outcomes and quality of life.	Physical activity is monitored for 7 days following paclitaxel infusion cycles 1, 6, 9, and 12. Each cycle is 7 days.
Primary	Identification of Body Composition Parameter (Muscle mass) Related to Dose-Limiting Toxicities (DLTs)	This outcome measure aims to identify specific parameters related to the body composition (muscle mass (Kg)) that influence the occurrence and severity of dose-limiting toxicities in breast cancer patients undergoing paclitaxel treatment.	Assessed through the 12-week treatment period, with measurements at baseline, cycles (each cycle is 7 days), 1 (week 1), 6 (week 6), 9 (week 9), and 12 (week 12).
Primary	Identification of Body Composition Parameters (Fat %) Related to Dose-Limiting Toxicities (DLTs)	This outcome measure aims to identify specific parameters related to the body composition (fat (%)) that influence the occurrence and severity of dose-limiting toxicities in breast cancer patients undergoing paclitaxel treatment.	Assessed through the 12-week treatment period, with measurements at baseline, cycles (each cycle is 7 days), 1 (week 1), 6 (week 6), 9 (week 9), and 12 (week 12).
Primary	Identification of Physical Activity Parameters Related to Dose-Limiting Toxicities (DLTs)	This outcome measure aims to identify specific parameters related to physical activity levels that influence the occurrence and severity of dose-limiting toxicities in breast cancer patients undergoing paclitaxel treatment.	Assessed through the 12-week treatment period, with measurements at baseline, cycles (each cycle is 7 days), 1 (week 1), 6 (week 6), 9 (week 9), and 12 (week 12).
Secondary	Paclitaxel Exposure Analysis (Cmax)	Evaluation of paclitaxel exposure by measuring blood serum concentrations to determine the maximum concentration remains above the threshold of 0.05 µmol/L, which is predictive of DLTs in breast cancer patients.	Blood samples collected and analyzed at cycles 1 (week 1), 6 (week 6), 9 (week 9), and 12 (week 12) post-paclitaxel infusion. Each cycle is 7 days.
Secondary	Paclitaxel Exposure Analysis (AUC)	Evaluation of paclitaxel exposure by measuring blood serum concentrations to determine the duration of time the concentration remains above the threshold of 0.05 µmol/L, which is predictive of DLTs in breast cancer patients.	Blood samples collected and analyzed at cycles 1 (week 1), 6 (week 6), 9 (week 9), and 12 (week 12) post-paclitaxel infusion. Each cycle is 7 days.
Secondary	Number and Type of Dose-Limiting Toxicities	Documentation and analysis of the number and type of DLTs experienced by participants, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) classification v5.0. This includes monitoring for neutropenia and chemotherapy-induced peripheral neuropathy among other toxicities.	DLTs recorded the week following paclitaxel infusion cycles 1, 6, 9, and 12 (each cycle is 7 days).

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