The Relationship Between Fat Free Mass and Toxicity of Cytostatics in Cancer Patients

An observational study of the relationship between fat free mass and toxicity of cytostatics in cancer patients, at the department of Clinical Oncology at Zealand University Hospital, Roskilde, Denmark. Fat free mass will be measured by bio impedance spectroscopy and data on toxicity will be obtained from medical records and interviews/questionnaires with the patients.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Pancreas Cancer
• Intervention / Treatment: Diagnostic test: Bio Impedance Spectroscopy (BIS)

Detailed Description

With a prospective observational design, this study will examine whether there is a correlation between the total dose of cytostatics per measured fat-free mass (FFM) (mg cytostatic agent/kg FFM) and toxicity of cytostatics among cancer patients. The study will include patients with a primary diagnosis of any stage colorectal or pancreatic cancer.

The hypothesis is, that a higher total dose of cytostatics per FFM will correlate to more frequent and/or more severe toxicity than a lower total dose. In extension to this, we hypothesize that a loss of FFM during treatment, and thereby an increased total dose of cytostatics per FFM, will lead to more frequent and severe toxicity.

Recruitment and data collection will take place at the department of Clinical Oncology at Zealand University Hospital, Roskilde over about a five month period. Each patient will be included for two-four cycles of cytostatic treatment. FFM will be measured by bio impedance spectroscopy as close to the first day of each cycle of cytostatic treatment as possible. Information about toxicity will be obtained from patient records and through interviews with the patients. Interviews will be conducted at day 5 (4-6) of each cycle and at the end of each cycle. The interviews include questionnaires about specific toxicities, using National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and overall health and quality of life, and 24-hour recall of dietary intake and questions about physical activity level.

In short, relevant outcomes are change in FFM, hematology, grade 3/4 hematological toxicity as defined by NCI CTCAE, dose-limiting toxicity, hospitalization, patient-reported adverse events, overall health and quality of life, and nutritional intake.

• Study Type: Observational
• Enrollment (Actual): 52

Contacts and Locations

Study Locations

• Denmark
  • Roskilde, Denmark, 4000
    • Zealand University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients at the department of Clinical Oncology at Zealand University Hospital, Roskilde, Denmark, who fulfills all inclusion criteria and none of the exclusion criteria.

Description

Inclusion Criteria:

• Authorized individuals
• Understands, speaks and reads Danish
• Patients referred for or who receives cytostatic treatment, and have a primary diagnosis of colorectal- or pancreatic cancer (diagnoses classified by International Classification of Diseases-10 as C18-21 and C25)
• Have the possibility of contact by telephone

Exclusion Criteria:

• Pregnancy
• Breastfeeding
• Dementia
• Contraindications for BIS measuring (pacemaker)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with cancer receiving cytostatic treatment; Consecutive patients referred for cytostatic treatment or in treatment with cytostatic agents for colorectal or pancreatic cancer	Diagnostic test: Bio Impedance Spectroscopy (BIS); Determination of fat free mass by BIS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fat free mass between cycles of cytostatic treatment (each cycle lasts for 14, 21 or 28 days, depending on the type of regime)	Changes in fat free mass, measured at baseline and the beginning of each cycle, between cycles of cytostatic treatment, and correlation with dose of cytostatic agent (mg) pr. fat free mass (kg)	During and between two-four cycles, depending on regime (each cycle is 14, 21 or 28 days, depending on the regime)
Leucocyte count (per cycle - see outcome 1)	Correlation between change i absolute and relative leucocyte count from baseline, and total dose of cytostatic agent (mg) pr. fat free mass (kg)	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Thrombocyte count (per cycle - see outcome 1)	Correlation between change i absolute and relative thrombocyte count from baseline, and total dose of cytostatic agent (mg) pr. fat free mass (kg)	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Mmol of haemoglobin/L (per cycle - see outcome 1)	Correlation between change i absolute and relative mmol of haemoglobin/L from baseline, and total dose of cytostatic agent (mg) pr. fat free mass (kg)	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Neutropenia	Correlation between incidence of absolute neutrophilic granulocyte count <1.0 - 0.5 x 10e9/L and total dose of cytostatic agent (mg) pr. fat free mass (kg)	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Febrile neutropenia	Correlation between incidence of absolute neutrophilic granulocyte count <1.0 x 10e9/L, with a single temperature of >38.3 degrees C or a temperature of >= 38 degrees C lasting for more than one hour, and total dose of cytostatic agent (mg) pr. fat free mass (kg)	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Anemia	Correlation between incidence of haemoglobin <4,9 mmol/L(; transfusion indicated) and total dose of cytostatic agent (mg) pr. fat free mass (kg)	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Thrombocytopenia	Correlation between incidence of absolute thrombocyte count <50.0 - 25.0 x 10e9 /L and total dose of cytostatic agent (mg) pr. fat free mass (kg)	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT)	Correlation between DLT and total dose of cytostatic agent (mg) pr. fat free mass (kg). DLT is defined as toxicity leading to one or more of the following: Dose reduction of one or more cytostatic agent(s) (recorded as mg and %). Postponement of cytostatic therapy (recorded as number of days). Discontinuation of cytostatic therapy before scheduled. Causes of DLT (that are registered in patients records) are classified in one or more of the following categories: Infection, organ impact, myelosuppression, gastrointestinal discomfort, neuropathy or other toxicity (which one is recorded).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Hospitalization	Hospitalization note in patient record. Correlation between incidence and number of days of hospitalization and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall health	Correlation between overall health, and change therein, the first 5 (4-6) days of a cycle or the last week of a cycle, evaluated on a 7-point scale, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Overall quality of life	Correlation between overall quality of life, and change therein, the first 5 (4-6) days of a cycle or the last week of a cycle, evaluated on a 7-point scale, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Energy intake (per cycle - see outcome 1)	Correlation between relative fulfilment of energy requirement, and change therein, on day 5 (4-6) of a cycle or the last day of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg), and change in fat free mass (kg). Energy requirement is estimated by Harris-Benedict formula, including among other assessment of physical activity level. Energy intake is assessed by 24-hour recall of nutrition intake.	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Protein intake (per cycle - see outcome 1)	Correlation between relative fulfilment of protein requirement, and change therein, on day 5 (4-6) of a cycle or the last day of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg), and change in fat free mass (kg). Protein requirement is estimated from the Danish Health Authority´s recommendation for adult patients. Protein intake is assessed by 24-hour recall of nutrition intake.	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Weight change (per cycle - see outcome 1)	Correlation between relative and absolute weight change, measured at the beginning of each cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg), and change in fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Difficulty swallowing	Correlation between patient reported severity and interference with daily activities of difficulty swallowing on a 5-point scale, and change therein, the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Mouth/throat sores	Correlation between patient reported severity and interference with daily activities of mouth/throat sores on a 5-point scale, and change therein, the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Taste changes	Correlation between patient reported severity of taste changes on a 5-point scale, and change therein, the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Decreased appetite	Correlation between patient reported severity and interference with daily activities of decreased appetite on a 5-point scale, and change therein, the first 5 (4-6) days of a cycle or the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Nausea	Correlation between patient reported frequency and severity of nausea on a 5-point scale, and change therein, the first 5 (4-6) days of a cycle or the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Vomiting	Correlation between patient reported frequency and severity of vomiting on a 5-point scale, and change therein, the first 5 (4-6) days of a cycle or the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Constipation	Correlation between patient reported severity of constipation on a 5-point scale, and change therein, the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Diarrhea	Correlation between patient reported frequency of diarrhea on a 5-point scale, and change therein, the first 5 (4-6) days of a cycle or the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Shortness of breath	Correlation between patient reported severity and interference with daily activities of shortness of breath on a 5-point scale, and change therein, the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Rash	Correlation between patient reported incidence of rash (yes/no), and change therein, of the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Hair loss	Correlation between patient reported degree of hair loss on a 5-point scale, and change therein, the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Hand-foot syndrome	Correlation between patient reported severity of hand-foot syndrome on a 5-point scale, and change therein, the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Numbness & tingling	Correlation between patient reported severity and interference with daily activities of numbness and tingling on a 5-point scale, and change therein, the first 5 (4-6) days of a cycle or the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
General pain	Correlation between patient reported frequency, severity and interference with daily activities of general pain on a 5-point scale, and change therein, the first 5 (4-6) days of a cycle or the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Fatigue	Correlation between patient reported severity and interference with daily activities of fatigue on a 5-point scale, and change therein, the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Nosebleed	Correlation between patient reported frequency and severity of nosebleed on a 5-point scale, and change therein, the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)
Other adverse event(s) added by patient	Correlation between patient reported severity of adverse event(s) on a 5-point scale, and change therein, the first 5 (4-6) days of a cycle or the last week of a cycle, and total dose of cytostatic agent (mg) pr. fat free mass (kg).	During two-four cycles, depending on regime (about eight-nine weeks), and within each cycle (each cycle is 14, 21 or 28 days)

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Collaborators: Zealand University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 4, 2020
• Primary Completion (ACTUAL): October 9, 2020
• Study Completion (ACTUAL): November 30, 2020

Study Registration Dates

• First Submitted: April 28, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (ACTUAL): August 27, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 29, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: adult; chemotherapy; quality of life; cancer; nutrition; adverse events; fat free mass; toxicity; lean body mass; dose-limiting toxicity; cytostatics
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: H-20000245

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No