NCT04507698招募中不适用
INTense Exercise foR surVivAL Among Men With Metastatic Castrate-Resistant Prostate Cancer (INTERVAL - MCRPC): A Multicentre, Randomised, Controlled, Phase III Study
适应症
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 5
- 主要终点
- Overall Survival
研究概览
简要总结
Exercise has been established to be safe and result in improved physical function and quality of life for most individuals with cancer. However, little information exists regarding whether exercise can increase overall survival and reduce disease progression, events related to cancer spreading to the bones (e.g. bone fracture, spinal cord compression, extra radiation or surgery), and pain in patients with metastatic prostate cancer that is no longer responding to hormone therapy. The primary objective of this study is to determine if high intensity aerobic and resistance training plus psychosocial support increases overall survival compared to psychosocial support alone in prostate cancer patients.
The Movember foundation is providing support for the conduct of this study
详细描述
Exercise as Non-Pharmacologic Adjuvant Therapy for Prostate Cancer:
Identifying and evaluating low-toxicity adjuvant interventions that can be combined with standard therapy to improve outcomes for men with prostate cancer is a high priority and has the potential to have a large impact on the clinical and public health burden of prostate cancer. The investigators summarise briefly below promising observational, pre-clinical, and pilot clinical data that support the hypothesis that exercise improves overall survival and health-related quality-of-life (QOL) among men with advanced prostate cancer:
- Vigorous aerobic exercise after diagnosis was associated with a 60% risk of fatal prostate cancer and a 49% risk of all-cause mortality among men initially diagnosed with localised disease.
- Loading of bone inhibited growth of metastatic tumours in animal models.
- Resistance exercise and programs with both resistance and aerobic exercise improved physical function and quality-of-life in men without metastases on androgen deprivation therapy (ADT) for prostate cancer.
- Treatment-related fatigue is a common side effect in men with advanced prostate cancer and exercise may decrease fatigue and increase adherence to treatment regimens.
- New standard treatments for advanced prostate cancer cause adverse metabolic effects (e.g., weight gain, insulin resistance) that may be avoided or attenuated by exercise.
Potential mechanisms of exercise influencing prostate cancer tumour biology
Potential mechanisms by which exercise may reduce the risk of prostate cancer progression, the incidence and progression of comorbidities, treatment side effects, and overall death among men with advanced prostate cancer include:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Patients must be mCRPC. This is defined as adenocarcinoma of the prostate with systemic metastatic disease despite castrate levels of testosterone (<50 ng/dL) due to orchiectomy or LHRH agonist.
- •Patients must have one or more of the following to be considered mCRPC
- •Metastatic Disease Progression: >20% increase in the sum of diameters of measurable lesions from the time of maximal regression or appearance of one or more new lesions.
- •Bone Scan Progression: Appearance of one or more new lesions on bone scan attributable to prostate cancer.
- •PSA Progression: PSA ≥2 ng/ml that has risen serially on at least two occasions, each at least one week apart (PSA1 < PSA2 < PSA3).
- •Castrate levels of testosterone must be maintained while on study. Be on androgen deprivation therapy (ADT) with a GnRH agonist/antagonist or prior bilateral orchiectomy. All patients will be required to be on ADT during the study period or have had a prior bilateral orchiectomy. Men with small cell neuroendocrine tumours or features of small cell disease are not eligible.
- •At enrolment, patients must fit into one of the following 5 categories:
- •Treatment naïve for mCRPC (have not yet started approved therapies for CRPC i.e.: Abiraterone/Enzalutamide/Apalutamide/Docetaxel; less than 4 weeks on approved therapies is still considered to be treatment naïve) Or
- •Receiving Abi/Enza/Apa for mCRPC AND responding or stable (PSA values must be stable or declining after at least 4 weeks since starting Abi/Enza/Apa for mCRPC) Or
- •Patients with PSA progression while on Abi/Enza/Apa are eligible as long as they are asymptomatic AND there is no intent on starting chemotherapy within 6 months Or
- •Patients treated with Docetaxel as first line therapy for mCRPC who are asymptomatic without ANY evidence of progression Or
- •Patients may have progressed following Docetaxel first line and are now receiving treatment with Abi/Enza/Apa. These patients must absolutely be responding or stable (PSA values must be stable or declining after starting Abi/Enza/Apa treatment) and have an expected life expectancy of more than 1 year.
- •4 weeks since last major surgery and fully recovered.
- •No known contraindications to high intensity exercise, including, but not limited to: brain metastases; current congestive heart failure(New York Heart Association Class II, III or IV); serious or non-healing wound, ulcer, or bone fracture; spinal cord compromise or instrumentation due to metastatic disease; peripheral neuropathy INTERVAL Protocol Version 4.0, 19 April 2018 4
- •No serious cardiovascular events within 12 months including, but not limited to, transient ischemic attack (TIA), cerebrovascular accident (CVA), or myocardial infarction (MI). Patients with a history of hypertension must be well-controlled (< 160/90) on anti-hypertensive therapy.
- •Halabi Nomogram score <1951 (Risk Category rated as low or intermediate risk)
- •Age ≥18 years
- •Required Baseline Laboratory Values: ANC ≥ 1500/uL; Platelet count ≥ 100,000/uL; Creatinine ≤ 1.5 x upper limits of normal; Bilirubin ≤ 1.5 x upper limits of normal; AST ≤ 1.5 x upper limits of normal; Serum testosterone ≤ 50 ng/dL
- •ECOG performance status 0-1
- •Medical clearance by treating physician to undergo a symptom-limited cardiopulmonary exercise test and vigorous aerobic and resistance exercise training, and able to complete an acceptable cardiopulmonary exercise test.
- •Exercise Coordination Centre (ECC) review and approval of subject's screening bone scan / areas with bone metastases.
- •Men participating in vigorous aerobic exercise for >60 min/week or structured resistance exercise ≥2 days/week, are not eligible.
- •Subject is willing and able to use technological aspects of the trial.
- •The subject is fluent in the language
排除标准
- •Previous radiographic or clinical progression (PSA progression is permitted) while on treatment with abiraterone, enzalutamide, apalutamide, or a combination.
- •Previously identified small cell neuroendocrine tumours or pure small cell carcinoma of the prostate, based on a prior biopsy of the prostate.
- •Brain metastases (brain imaging is not required)
- •Previous and/or concurrent treatment with other anti-cancer treatments is permitted. Patients are allowed to be treated with chemotherapy during the duration of the trial. Patients who have received chemotherapy as part of initial androgen deprivation therapy for metastatic castration sensitive disease are eligible.
- •Currently receiving experimental treatment with non-approved drugs at the time of enrolment. Patients must undergo a 28-day washout between last dose and screening CPET.
- •Poorly controlled hypertension. During screening ≥2/3 of readings must be < 160/90, regardless of whether on a regimen of anti-hypertensive therapy or not.
- •If patient is currently taking hypertensive medication(s)/therapy, please indicate medication and include in the Treatment and Concomitant Medications Log (SOM: Appendix 11).
- •Current congestive heart failure (New York Heart Association Class II, III or IV)
- •Recent serious cardiovascular events (within 12 months) including, but not limited to, transient ischemic attack (TIA), cerebrovascular accident (CVA), or myocardial infarction (MI).
- •Medical condition such as uncontrolled infection or cardiac disease that, in the opinion of the physician, would make this protocol unreasonably hazardous for the patient.
- •Patients with a currently active second malignancy other than non-melanoma skin cancer. Patients are not considered to have a currently active malignancy if they have completed necessary therapy and are considered by their physician to be at <30% risk of relapse at time of assessment.
- •Psychiatric illness, which would prevent the patient from giving informed consent or adhering to the study protocol.
- •Serious or non-healing wound, ulcer, or bone fracture.
- •Known spinal cord compromise or instrumentation due to metastatic disease in the mCRPC state. Radiation therapy for metastatic disease is allowed.
- •Peripheral neuropathy ≥grade
- •Men participating in vigorous aerobic exercise for more than 60 minutes per week or structured INTERVAL Protocol Version 4.0, 19 April 2018 15 Resistance exercise two or more days per week (seek ECC approval before exclusion).
- •Experiences shortness of breath, chest discomfort, or palpitations when performing activities of daily living (patient with these symptoms can participate in the study with cardiologist clearance)
- •Ongoing restriction of physical activity with physician documentation
- •Has chest pain brought on by physical activity (patient can participate in the study with cardiologist clearance)
- •Has developed chest pain in the past month (patient can participate in the study with cardiologist clearance)
- •Moderate-to-severe bone pain (i.e., National Cancer Institute's Common Terminology Criteria for Adverse Events grade 2-3 bone pain).
- •Men who do not complete the baseline lifestyle and quality-of-life questionnaires and 3-days of diet diaries or country-specific FFQ will not be eligible
结局指标
主要结局
Overall Survival
时间窗: 24 months
Patients will be followed for death a minimum of 36 months after randomisation. Overall survival will be measured from the time of randomisation until death. Medical records and death certificates will be reviewed every 6 months to obtain survival status. Country-specific mortality status databases will also be searched annually; cause of death will be determined through review of medical and death records. Patients will be contacted once a year, and follow up with next of kin then alternate contact, if needed, if we do not hear from them.
次要结局
- Symptomatic Skeletal Related Events(24 months)
- Disease progression(24 months)
- Analgesic/Opiate Use(24 months)
- Metabolic Biomarkers(24 months)
- Physical Function(24 months)
- Quality of Life - Patient Reported Outcome Measures(24 months)
研究者
研究点 (5)
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