Measuring Oncological Value of Exercise and Statin

Trial Title: Measuring Oncological Value of Exercise and Statin

NCT ID: NCT05796973

Condition: 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

Conditions: Official terms:
Breast Neoplasms
Prostatic Neoplasms
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Carcinoma, Renal Cell
Kidney Neoplasms
Atorvastatin

Study type: Interventional

Study phase: Phase 3

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

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

Masking: None (Open Label)

Intervention:

Intervention type: Behavioral
Intervention name: Guided physical exercise
Description: Patients will be participating in guided physical exercise program regularly two times / week at a sports facility and guided by a professional trainer. They will participate in aerobic and resistance exercises during the sessions.
Arm group label: Atorvastatin arm
Arm group label: Guided physical exercise arm

Intervention type: Drug
Intervention name: Atorvastatin
Description: Patients will be participating in guided physical exercise program regularly two times / week at a sports facility and guided by a professional trainer. They will participate in aerobic and resistance exercises during the sessions. In addition to the exercise program they will be given atorvastatin 40 mg QD medication.
Arm group label: Atorvastatin arm

Intervention type: Other
Intervention name: Independent exercise
Description: 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.
Arm group label: Non-guided physical exercise arm

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.

Criteria for 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)

Gender: All

Minimum age: 18 Years

Maximum age: 99 Years

Healthy volunteers: No

Locations:

Facility:
Name: Tampere University Hospital

Address:
City: Tampere
Zip: 33520
Country: Finland

Status: Recruiting

Contact:
Last name: Teemu Murtola, MD PhD Prof
Email: teemu.murtola@tuni.fi

Contact backup:
Last name: Jorma Sormunen, MD PhD MBA
Email: jorma.sormunen@fimnet.fi

Start date: March 31, 2023

Completion date: December 31, 2027

Lead sponsor:
Agency: Tampere University Hospital
Agency class: Other

Collaborator:
Agency: Tampere University
Agency class: Other

Collaborator:
Agency: Aalto University
Agency class: Other

Collaborator:
Agency: University of Helsinki
Agency class: Other

Collaborator:
Agency: University of Turku
Agency class: Other

Source: Tampere University Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05796973