Clinical trial NCT05796973: Measuring Oncological Value of Exercise and Statin
Official title: Syöpäpotilaan Ennusteen Parantaminen Muuttamalla syövän mikroympäristöä ja Metaboliaa Liikunnalla ja lääkkeellisesti - Measuring Oncological Value of Exercise and Statin
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Prostate Cancer
Breast Cancer
Kidney Cancer
Ovarian Cancer
Metastatic Breast Cancer
Metastatic Kidney Cancer
Metastatic Renal Cell Carcinoma
Metastatic Renal Cancer
Metastatic Prostate Cancer
Metastatic Prostate Adenocarcinoma
Metastatic Ovarian Cancer
Metastatic Ovary Cancer
Lead sponsor: Tampere University Hospital
Sponsor class: OTHER
Collaborators: name: Tampere University
name: Aalto University
name: University of Helsinki
name: University of Turku
First posted: 2023-04-04
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The patients are randomized equally into three groups: 1/3 into guided exercise group, 1/3 into guided exercise and statin-treatment group and 1/3 into non-guided exercise group
Primary purpose: TREATMENT

Brief summary: The aim of the study is to find out whether supervised physical exercise during cancer drug treatment improves the effectiveness of the treatment in metastasized breast, kidney, ovarian and prostate cancer compared to unsupervised exercise. In addition, the investigators are investigating whether the use of atorvastatin combined with guided group exercise training would further improve the response to cancer treatment.

Detailed description: Despite the marked differences between different malignancies' genetic, metabolic, and prognostic factors, hypoxia and adaptation of metabolic changes favoring hypoxic microenvironment are common factors in most solid tumors. Hypoxic microenvironment provides cancer cells multiple advantages: protection from immune system, somatic mutations leading to more aggressive form of cancer, and cancer cells that are adjusted to hypoxic conditions are more prone to form metastases. One possible mechanism for cancer cell to adjust to hypoxic microenvironment is related to lipid metabolism; lipids are known to accumulate into cancer cells in many cancer types. One of the most promising ways to reduce hypoxia in solid tumors is to increase physical exercise. Furthermore, tumors' lipid metabolism can be affected by treatment with cholesterol-lowering statins, which decreases serum cholesterol levels and inhibits cancer cells' own lipid synthesis.

The aim of this randomized clinical trial is to investigate if supervised group exercise will improve response to cancer drug treatment in metastasized breast, kidney, prostate, and ovarian cancer compared to unsupervised exercise. The investigators will also evaluate if atorvastatin treatment in combination with guided group exercise can promote even better treatment responses than exercise alone. Exercise program includes aerobic and resistance training.

This study is a randomized phase III pilot study testing the research hypothesis for the first time in humans. In the pilot phase of the study, a total of 240 cancer patients (n=60/cancer type) will be recruited into the study and randomized 1:1:1 into three different groups, i.e. 20 people in each group from each cancer type:

1. 3 months of supervised group exercise
2. 3 months of supervised group exercise and at the same time atorvastatin 40 mg/day
3. to a control group that exercises voluntarily without guidance

In addition, as a separate group, a total of 160 cancer patients (40/cancer type) who are already using statin medication will be recruited for the study and randomized 1:1 into two groups: 1) 3 months of supervised group exercise and 2) independent exercise (a control group that exercises voluntarily without guidance).

Before the study begins, the patients are informed orally and in writing about the study. The patients who agree to participate in the study sign an informed consent.

The patient follow-up time in each group is two years in 3 months intervals (first visit and 8 follow-up visits) in conjunction with standard cancer treatment follow-up visits. Blood and urine samples and questionnaire data are collected at baseline and at each follow-up visit. Body composition and physical performance are measured at baseline and twice after the intervention. Patients QoL and experiences of exercise are measured in qualitative interviews (in the group participating the qualitative sub-study).

The main response variables are

1. cancer progression during cancer treatment based on imaging, symptoms or laboratory findings and
2. mortality of the patients.

   The other variables of interest in this study are:
3. whether exercise alone reduces hypoxia sufficiently to improve the effectiveness of cancer chemotherapy, and whether inhibiting lipid synthesis with a statin enhances this effect.
4. to evaluate the patient's experiences of cancer drug treatment, their side effects and the effects of increasing exercise on the patient's perceived quality of life, perceived pain, depressive symptoms, nutrition and relationships.

Adverse events from cancer treatment and treatment interruptions are also monitored.

Eligibility criteria: Inclusion Criteria:

* The patient has metastatic prostate cancer, breast cancer, ovarian cancer or kidney cancer confirmed histologically and by imaging, for which 1st-line cancer drug treatment is started
* Prostate cancer: First course of docetaxel treatment for metastatic prostate cancer.
* Breast cancer: First-line medical treatment of metastatic breast cancer regardless of hormone receptor status.
* Kidney cancer: medium-risk/high-risk kidney cancer according to the IMDC classification, for which 1st-line cancer drug treatment is started as tki monotherapy or as a combination treatment that includes tki medication. - the randomization of subjects is stratified according to gender
* Ovarian cancer: stage III or IV cancer for which 1st-line chemotherapy treatment is started.
* The patient agrees to the study and signs a written informed consent.
* Adult (18 years=\>) women (breast, ovarian and kidney cancer) and men (prostate and kidney cancer) are recruited for the study.
* In women, the use of a reliable contraceptive during the intervention

Exclusion Criteria:

* High risk of bone fractures
* Inability to physical exertion and/or unsuitability for cancer drug treatment
* Poor co-operation ability for psychological reasons
* Active use of cholesterol-lowering drugs
* Severe liver or kidney failure
* Troublesome side effects that occurred in the past during cholesterol medication
* Continuous use of medicinal substances that interact with atorvastatin during the study period
* A special group of subjects according to the Medical Research Act (1999/488) (e.g. minors and pregnant or lactating women)

Exclusion criteria in patients who are already using statin medication before the study:

* High risk of bone fractures
* Inability to physical exertion and/or unsuitability for cancer drug treatment
* Poor co-operation ability for psychological reasons
* Severe liver or kidney failure
* A special group of subjects according to the Medical Research Act (1999/488) (e.g. minors and pregnant or lactating women)

Primary outcomes:
measure: Time to cancer progression
timeFrame: From randomization until the date of first documented progression, assessed at twelve week intervals up to 24 months
measure: Mortality
timeFrame: From randomization until the date of death, assessed up to 24 months
Secondary outcomes:
measure: Hypoxia markers in serum (VEGF, HIF1-alpha, carboanhydrase IX, LADH)
timeFrame: At baseline and at 3 months
measure: Tolerability of treatment
timeFrame: From date of randomization, assessed at twelve week intervals up to 24 months
measure: Fat/muscle ratio as measured with impedance test
timeFrame: At baseline and at 3 and 6 months
measure: Physical performance with standardized muscle strength tests
timeFrame: At baseline and at 3 and 6 months
measure: Changes in tissue hypoxia
timeFrame: At baseline and at 3 months
measure: Changes in quality of life
timeFrame: At baseline and at 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and 24 months
measure: Depressive symptoms
timeFrame: At baseline and at 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and 24 months
measure: Severity of pain
timeFrame: At baseline and at 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and 24 months
measure: Nutritional status
timeFrame: At baseline and at 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and 24 months
measure: Relationship satisfaction
timeFrame: At baseline and at three months, twelve months and 24 moths.
Other outcomes:
Locations:
city: Tampere
country: Finland
facility: Tampere University Hospital
state: Länsi-Suomi
Study officials:
affiliation: Tampere University Hospital
name: Teemu Murtola, MD PhD Prof
role: PRINCIPAL_INVESTIGATOR
References: