Measuring Oncological Value of Exercise and Statin (MOVES)

Tampere University Hospital

Status and phase: Enrolling; Phase 3

Conditions: Breast Cancer; Metastatic Prostate Cancer; Metastatic Renal Cell Carcinoma; Metastatic Prostate Adenocarcinoma; Metastatic Renal Cancer; Metastatic Ovarian Cancer; Ovarian Cancer; Metastatic Kidney Cancer; Metastatic Ovary Cancer; Kidney Cancer; Metastatic Breast Cancer; Prostate Cancer

Treatments: Behavioral: Guided physical exercise; Other: Independent exercise; Drug: Atorvastatin

Study type: Interventional

Funder types: Other

Identifiers

NCT05796973

2019-001982-34

Details and patient eligibility

About

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.

Full 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 study testing the research hypothesis for the first time in humans. 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. Hypoxia markers

4. Tolerability of treatment

5. Body composition

6. Physical performance

7. The extent of hypoxia, as measured by PET scans, in participants of the sub-study

4. Quality of life, perceived pain, depressive symptoms, nutrition and relationships.

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

Enrollment: 240 estimated patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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 or second-generation antiandrogen treatment for metastatic prostate cancer.
• Breast cancer: First-line medical treatment of metastatic breast cancer regardless of hormone receptor status.
• Kidney cancer: Kidney cancer, for which 1st-line cancer drug treatment is started as tki monotherapy and/or IO monotherapy or as a combination therapy.
• Ovarian cancer: stage III or IV cancer for which 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 EU Clinical Trials Regulation 536/2014 (e.g. 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 EU Clinical Trials Regulation 536/2014 (e.g. pregnant or lactating women)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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240 participants in 3 patient groups

Guided physical exercise arm

Experimental group

Description:

20 patients from each type of cancer (altogether 80) are randomized to a 3 months guided physical exercise arm. At the beginning of the intervention the patients' physical condition and body composition are measured. After that an exercise program begins. All subjects participate in physical exercise program twice a week for three months. At the end of the intervention, the physical condition and body composition are measured again. During the follow-up after the intervention the patients are advised to exercise regularly. Physical condition and body composition are measured again after 6 months. Exercise activity is asked during each follow-up visit. In addition, as a separate group, 20 patients from each type of cancer (altogether 80) who are already using statin medication are randomized to this arm.

Treatment:

Behavioral: Guided physical exercise

Atorvastatin arm

Experimental group

Description:

20 patients from each type of cancer (altogether 80) are randomized to a 3 months guided physical exercise + atorvastatin (40 mg QD) arm. At the beginning of the intervention the patients' physical condition and body composition are measured. After that an exercise program begins. All subjects participate in physical exercise program twice a week for three months. At the end of the intervention, the physical condition and body composition are measured again. During the follow-up after the intervention the patients are advised to exercise regularly. Physical condition and body composition are measured again after 6 months. Exercise activity is asked during each follow-up visit.

Treatment:

Drug: Atorvastatin

Behavioral: Guided physical exercise

Non-guided physical exercise arm

Active Comparator group

Description:

20 patients from each type of cancer (altogether 80) are randomized to a non-guided physical exercise arm. The patients' physical condition and body composition are measured at baseline. The control group is advised of the benefits of physical exercise and they get an exercise program to follow. Participants in the control group exercise on their own. The physical condition and body composition of this group is also measured at three months and six months after baseline to detect changes. After that the patients are given advise to exercise regularly and this is asked during each follow-up visit. In addition, as a separate group, 20 patients from each type of cancer (altogether 80) who are already using statin medication are randomized to this arm.

Treatment:

Other: Independent exercise