Syöpäpotilaan Ennusteen Parantaminen Muuttamalla syövän mikroympäristöä ja Metaboliaa Liikunnalla ja lääkkeellisesti - Measuring Oncological Value of Exercise and Statin
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Time to cancer progression
研究概览
简要总结
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.
详细描述
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:
- 3 months of supervised group exercise
- 3 months of supervised group exercise and at the same time atorvastatin 40 mg/day
- 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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
Guided physical exercise arm
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.
干预措施: Guided physical exercise (Behavioral)
Atorvastatin arm
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.
干预措施: Guided physical exercise (Behavioral)
Atorvastatin arm
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.
干预措施: Atorvastatin (Drug)
Non-guided physical exercise arm
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.
干预措施: Independent exercise (Other)
结局指标
主要结局
Time to cancer progression
时间窗: From randomization until the date of first documented progression, assessed at twelve week intervals up to 24 months
Radiological progression • Radiological progression of the disease according to RECIST criteria (version 1.1.) compared to the situation at the start of cancer treatment in all cancer types. If the cancer treatment includes the use of immune checkpoint inhibitors, the imRECIST criteria are applied to evaluate the response In addition, the disease is considered advanced if both of the criteria below are met: * Biochemical progression: * PSA progression in prostate cancer, (three consecutive PSA increases measured at least one week apart, two \> 50% increases from the lowest PSA level and PSA \> 2 ng/ml) with testosterone at castration level (\< 50 ng/ml or 1.7 nmol/l) * Ca15-3 marker increase in breast cancer (three consecutive marker increases that the clinician considers significant) * In ovarian cancer, ca12-5 marker increase (three consecutive marker increases that the clinician considers significant) * Clinical progression o ECOG 3 or less (long-term)
Mortality
时间窗: From randomization until the date of death, assessed up to 24 months
Time to death from the beginning of the first-line medication
次要结局
- Hypoxia markers in serum (VEGF, HIF1-alpha, carboanhydrase IX, LADH)(At baseline and at 3 months)
- Tolerability of treatment(From date of randomization, assessed at twelve week intervals up to 24 months)
- Physical performance with standardized muscle strength tests(At baseline and at 3 and 6 months)
- Relationship satisfaction(At baseline and at three months, twelve months and 24 moths.)
- Fat/muscle ratio as measured with impedance test(At baseline and at 3 and 6 months)
- Changes in tissue hypoxia(At baseline and at 3 months)
- Changes in quality of life(At baseline and at 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and 24 months)
- Depressive symptoms(At baseline and at 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and 24 months)
- Severity of pain(At baseline and at 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and 24 months)
- Nutritional status(At baseline and at 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and 24 months)
研究者
Teemu Murtola
Professor of Urology, Chief Physician
Tampere University Hospital