Clinical trial NCT01642680: Optimal Timing of Physical Activity in Cancer Treatment
Official title: Optimal Timing of a Tailored Physical Activity Program During Chemotherapeutic Cancer Treatment to Reduce Long-term Cardiovascular Morbidity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Vascular Disorders
Cardiovascular Risk Factors
Fatigue
Keywords: Physical activity program
Chemotherapy
Metabolic syndrome
Reducing cardiovascular risk factors
low physical activity level
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2012-07-17
Enrollment: 266
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The number of long-term cancer survivors is growing. As a result, treatment-related morbidity - such as cardiovascular disease, metabolic syndrome, functional decline and fatigue - is impacting quality of life and impairing survival. Metabolic syndrome in the general population is currently treated with lifestyle advice to increase physical activity (PA) and reduce caloric intake. This approach is still underused as standard care for cancer survivors. The aim of this study is investigate whether a tailored PA program that starts early (during curative chemotherapy with cardiovascular toxic potential) is superior in terms of reducing long-term cancer-treatment-related metabolic syndrome and cardiovascular morbidity to a program that starts late (after completion of chemotherapy).

Detailed description: Improved treatment is partly responsible for the increased survival and life expectancy in cancer patients. However, such treatment can be harmful as well, and cancer survivors therefore, face an increased risk of second malignancies and other chronic diseases, e.g. cardiovascular diseases and metabolic syndrome.

Due to the growing number of cancer patients and survivors, attention for rehabilitation, especially physical training, is growing. Several meta-analyses show the beneficial effects of physical training on several outcomes such as physical fitness, muscle strength, fatigue and quality of life, and a few studies showed the effect of exercise on physical active behaviour. However, studies on the effect of timing of exercise are lacking.

The present study aims to insert a tailored physical activity program early versus late in the chemotherapy based cancer treatment and will yield data about its safety and efficacy. We hypothesize that a tailored physical activity program during early cancer treatment may more be effective to reduce long-term cancer treatment toxicities and morbidity in cancer survivors compared to a program after cancer treatment.

Primary Objective: To investigate whether a tailored physical activity program that starts during chemotherapy (early) is superior in terms of physical fitness, as determined by VO2 peak at one year, to a program that starts after completion of chemotherapy (late).

Secondary Objectives: To examine the effect of the physical activity program on muscle strength and activity level, change in metabolic and cardiovascular damage parameters, cardiovascular risk factors and quality of life including self-efficacy, motivation for exercise, and fatigue.

Design: This protocol describes a multicenter, randomized study with 2 arms. Patients who will be treated with curative systemic chemotherapeutic treatment for testicular cancer, early colon cancer, early breast cancer or B-NHL will be randomized into an early or late PA program group. The early group will start the PA program during chemotherapy (for 12 weeks) until 12 weeks after completion of chemotherapy (total 24 weeks of training). The late group will start the same program (total of 12 weeks) after completion of chemotherapy. The longitudinal effects of the physical activity (PA) program for all participants will be evaluated at different time points in the UMCG: before start of chemotherapeutic treatment; at the start of the PA program and at 3, 6, 18 months after starting the PA program and 18 months after the last chemotherapy.

Eligibility criteria: Inclusion Criteria:

* Patients with testicular, early colon, breast cancer or B-NHL with an indication for systemic chemotherapy with a curative intent
* Normal blood count at start of systemic treatment
* Patients need to have an adequate physical health, which is defined by diastolic blood pressure \>45 mm Hg or \<95 mm Hg; heart frequency in at rest \< 100 per minute; body temperature below 38°C; respiration frequency in rest below 20 per minute
* Adequate cardiac function with a LVEF above the lower limit of normal
* Written informed consent

Exclusion Criteria:

* Infections requiring actual antibiotics
* Signs of ongoing bleeding or fresh petechiae; unexplained bruises
* Critical organ impairment due to their malignancy
* Not recovered from earlier surgical intervention
* Non adequate control of any symptoms of the malignancy
* Inability to travel independently to the rehabilitation centre
* Cognitive disorder or emotional instability that might impede the participation in the training program
* Recent cardiovascular event

Primary outcomes:
measure: Difference in VO2 peak between the groups after completion of the PA program, measured by cardiopulmonary exercise testing (CPET).
timeFrame: 1,5 year
Secondary outcomes:
measure: Muscle strength using a hand-held dynamometer
timeFrame: 1,5 year
measure: Intima media thickness will be measured with vascular ultrasound
timeFrame: 1,5 year
measure: Cholesterol levels, measured in blood
timeFrame: 1,5 year
measure: Triglyceride levels, measured in blood
timeFrame: 1,5 year
measure: Glucose levels, measured in blood
timeFrame: 1,5 year
measure: Body mass index, calculated with formula (see below)
timeFrame: 1,5 year
measure: Health related quality of life measured with the EORTC QLQ-C30
timeFrame: 1,5 year
measure: Patient reported self-efficacy measured using the ALCOS instrument
timeFrame: 1 year
measure: Patient reported fatigue measured with the Multi-dimensional Fatigue Inventory
timeFrame: 1,5 year
measure: Patient reported physical activity level with the PASE questionnaire
timeFrame: 1,5 year
measure: DNA collection
timeFrame: 1,5 year
measure: Diffusion capacity of the lungs
timeFrame: 1,5 year
measure: Forced vital capacity (FVC) will be assessed by use of dynamic spirometry
timeFrame: 1,5 year
measure: Forced expiratory volume in one second (FEV1) will be assessed by use of dynamic spirometry,
timeFrame: 1,5 year
measure: FEV1/FVC ratio will be assessed by use of dynamic spirometry,
timeFrame: 1,5 year
measure: Senescence with markers of the senescence- associated secretory phenotype
timeFrame: 1,5 year
measure: Cardiac function with echocardiography (Ultrasound technique)
timeFrame: 1,5 year
measure: Body composition will be assessed with a DEXA scan
timeFrame: 1,5 year
measure: PAI-antigen, measured in blood serum
timeFrame: 1,5 year
measure: t-PA, measured in blood serum
timeFrame: 1,5 year
measure: Factor VIII, measured in blood serum
timeFrame: 1,5 year
measure: Von Willebrand factor, measured in blood serum
timeFrame: 1,5 year
measure: Fibrinogen, measured in blood serum
timeFrame: 1,5 year
measure: Advanced glycation end products (AGEs) will be determined by measuring skin auto fluorescence.
timeFrame: 1,5 year
measure: Blood pressure, measured with a blood pressure cuff
timeFrame: 1,5 years
measure: Fat percentage with skinfold measurement
timeFrame: 1.5 years
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Centre Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Annemiek Walenkamp, PhD
role: PRINCIPAL_INVESTIGATOR
References: