Clinical Trials /

INTERVAL - Intense Exercise Trial for Men With Metastatic Castrate-Resistant Prostate Cancer

NCT04507698

Description:

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

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: INTERVAL - Intense Exercise Trial for Men With Metastatic Castrate-Resistant Prostate Cancer
  • Official Title: INTense Exercise foR surVivAL Among Men With Metastatic Castrate-Resistant Prostate Cancer (INTERVAL - MCRPC): A Multicentre, Randomised, Controlled, Phase III Study

Clinical Trial IDs

  • ORG STUDY ID: 201101
  • NCT ID: NCT04507698

Conditions

  • Prostate Cancer

Purpose

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

Detailed Description

      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:

      Endocrine - Exercise influences all hormonal systems in the body with key hormones relevant
      to prostate cancer being testosterone, growth hormone, and insulin-like growth factor-1
      (IGF-I). The androgen receptor and its transactivation by ligand are one of the most
      important determinants of prostate cancer progression. Measurements of serum androgens
      provide an important biomarker for effectiveness of androgen deprivation and prostate cancer
      progression. Current studies are inconclusive as to the effects of exercise on serum androgen
      levels. In part, these studies are limited by low patient numbers and inadequate methods for
      measuring testosterone levels in the low ranges seen in men on androgen deprivation therapy.
      This is especially true with the cyp17 inhibitors, such as Abiraterone.

      Immune System, Inflammation, and Cytokines - High levels of inflammatory biomarkers are
      associated with an increased risk of prostate cancer-specific mortality, and exercise is
      known to levels of circulating inflammatory biomarkers (e.g., interleukin- 6 (IL-6)) in
      elderly populations. In addition, exercise may enhance natural killer cell cytotoxicity and
      immune surveillance, improving immune defence against prostate cancer. Further, adipokines
      may also have pro- or anti-oncogenic roles in angiogenesis and cell proliferation. For
      example, adiponectin has anti-inflammatory effects and its serum concentration is inversely
      correlated with adiposity. Resistin is associated with insulin resistance through AMP kinase
      down-regulation. It up-regulates pro-inflammatory cytokines (IL-6, tumour necrosis factor
      alpha (TNFα)) which act via the nuclear factor kappa-light-chain-enhancer of activated B
      cells (NFκb) pathway to increase transcription of proteins involved in cell proliferation,
      inflammation and anti-apoptosis. In addition, activation of NFκb is implicated in prostate
      cancer, nuclear expression being associated with nodal metastasis. IL-6 and TNFα are both
      elevated in the serum of patients with metastatic carcinoma compared to patients without
      metastases. Interestingly, both are elevated in prostate carcinoma in direct proportion to
      disease stage, and increases occur at the time of biochemical (PSA) disease progression.

      Energy Metabolism - Exercise improves insulin sensitivity and glucose metabolism. While ADT
      in principle is targeting the prostate cancer tumour, the systemic treatment in patient's
      results in a range of alterations associated with metabolic syndrome. One of the earliest
      changes following ADT, within 2-6 a reduction in insulin sensitivity leading to a rise in
      circulating insulin (hyperinsulinemia); the rise in insulin levels precedes changes in
      adiposity and increased lipids, sarcopenia, and bone loss. High insulin levels are predictive
      of more rapid progression to CRPC, and poor prognosis. Insulin has been shown to have a
      direct action on prostate cancer growth and progression, and this can be inhibited by
      blocking insulin action. Additionally, high levels of C-peptide, a marker of insulin
      secretion, are associated with a more than 2-fold increased risk of prostate cancer-specific
      mortality. Further, over the (body mass index (BMI) >25 kg/m2) men with high C-peptide levels
      had a more than 4-fold increased risk of prostate cancer-specific mortality compared to
      normal the men with low C-peptide levels.

      Body composition - Cancer and its treatments cause substantial changes in body composition
      with sarcopenic obesity being a common outcome. This not only results in substantial
      impediment to functional ability and increased cardio-metabolic risk, but also alteration of
      adipokine and myokine balance, which may contribute to tumour progression. Exercise increases
      lean muscle mass and may cause loss of fat mass, thereby improving overall body composition.

      Epigenetics - Exercise can produce epigenetic modulations that may inhibit tumour cell
      proliferation, such as altering histone deacetylase pathways.

      Telomere - Short and/or variable telomere length in the prostate is a prognostic marker among
      men with prostate cancer. One study among 10 men with localised prostate cancer on active
      surveillance reported that a lifestyle program that included moderate exercise (as the as
      diet, stress management, and social support) increased telomere length in blood.

      Cholesterol - Epidemiological studies have suggested that high levels of cholesterol in the
      blood are associated with increased risk of prostate cancer and progression of prostate
      cancer. Exercise combined with dietary modification has been demonstrated to substantially
      reduce total cholesterol as the as improve the ratio of high density lipoprotein to low
      density lipoprotein cholesterol.

      Oxidative stress - Exercise has been demonstrated to modulate oxidative stress and improve
      antioxidant capacity. In a pilot study at the University of California, San Francisco, men
      with low risk, localised prostate cancer who reported ≥3 hours/the of vigorous physical
      activity had modulated expression of the nuclear factor erythroid 2-related factor 2 (Nrf-2)
      mediated oxidative stress response pathway in their normal prostate tissue compared to men
      who did less exercise. Oxidative stress is hypothesized to play a significant role in the
      initiation and progression of prostate cancer.

      As the burden of disease among men with prostate cancer advances, a rapid, significant
      deterioration in QOL is observed. Bone pain which is reported in up to 80% of patients with
      metastatic disease throughout their treatment, makes the largest single contributor to QOL
      deterioration in this population. Other symptoms which compromise QOL include urinary
      frequency, sexual dysfunction, nausea and vomiting, loss of appetite and dyspnoea. The
      benefits of exercise training on QOL for men with non-metastatic prostate cancer are the
      described, and include improvements in general QOL and also cancer-specific concerns
      including fatigue and sexual health. Whether exercise can improve QOL among men at the end
      stage of this disease is not known.

      Metastatic spread of prostate cancer occurs primarily to sites in the axial skeleton
      including the femur, pelvis and vertebrae. Metastatic lesions, which are typically
      osteoblastic, lead to significant bone pain and compromised skeletal quality. Skeletal
      complications, such as bone fractures, orthopaedic intervention or spinal cord compression,
      which develop due to bone metastases, result in significant patient morbidity and compromised
      QOL. Furthermore, compared to those who do not experience a symptomatic skeletal related
      event (SSE), the occurrence of a SSE is associated with increased patient mortality. A
      modular multi-modal approach to exercise training involving individualised prescription of
      exercise to reduce the forces going through the bone has been shown to be safe and feasible
      in men with bony metastases and not associated with increased risk of pathological fracture.
      This proposal will test whether exercise training delays time to SSE as the time to
      progression of pain and affects measures of pain severity and opiate use. Control or relief
      of pain and delay or prevention of SSE are both indications for approved therapeutic agents
      for men with metastatic prostate cancer.

      In addition to SSE and pain due to the infiltration of metastatic prostate cancer in bone,
      men with this disease also experience debilitating cancer-related fatigue and adverse
      cardio-metabolic health as a side effect of therapy. Cancer-related fatigue is a distinct
      phenomenon from fatigue experienced by healthy individuals and significantly health-related
      QOL. There are extensive data to support that exercise improves fatigue in men with a disease
      burden. This proposal will be the first to examine whether exercise improves or delays onset
      of cancer-related fatigue in men with metastatic prostate cancer.

      Rationale for Focus on Metastatic Castrate-Resistant Prostate Cancer (MCRPC), our overarching
      objective is to determine the effect of exercise on overall survival among men with advanced
      prostate cancer. The investigators have chosen to restrict our study population to men with
      progressive MCRPC because: 1) Men with progressive MCRPC are at high risk for death within a
      time frame that can be feasibly tested in the setting of a RCT (median OS on treatment = 3242
      to 3543 months). 2) With the proper use of stratification variables (treatment and study
      site), it is possible to define a homogenous study population in terms of risk of death; 3)
      This is the largest group of patients that can be uniformly considered to have advanced
      prostate cancer and thus provides the largest patient pool for recruitment while also meeting
      criteria 1 & 2; 4) while new therapies for MCRPC extend life, they also cause significant
      harm to metabolic and cardiac function and health-related QOL which may be attenuated or
      avoided through exercise; and 5) the investigators hypothesize that exercise will have the
      largest measurable effect on OS among men with documented evidence of progressing MCRPC (in
      contrast to men with stable M1 CRPC, non-castrate resistant disease, or non-metastatic
      disease).

      The primary endpoint for this randomised controlled trial will be overall survival (OS). OS
      was chosen as the primary endpoint because it has clear biological, clinical and public
      health significance and is a validated endpoint for approval of new treatments among men with
      MCRPC. Additionally, OS data can be obtained with minimal loss to follow-up through review of
      medical and death records. The median OS among men with MCRPC is 3242 to 3543 months. Thus,
      OS is a feasible outcome to examine within the budget and timeline of the proposed study.
    

Trial Arms

NameTypeDescriptionInterventions
Supervised Exercise ArmExperimentalIf participants are placed in the Supervised Exercise Group, they will attend supervised group exercise sessions, which are individually tailored to the participants physical condition, at least once a week, every week for the first year of the study. They will be asked to exercise 3 times a week.
    Self-Directed Exercise ArmNo InterventionIf Participants are placed in the Self-directed Exercise Group, they will receive usual medical care (standard of care) and be asked to follow their usual exercise and lifestyle routine. They will receive supportive care in the form of newsletters, covering a variety of topics including pain management, bone health, goal setting, taking control of life, and more.

      Eligibility Criteria

              Inclusion Criteria:
      
                -  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:
      
                     1. 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
      
                     2. 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
      
                     3. 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
      
                     4. Patients treated with Docetaxel as first line therapy for mCRPC who are
                        asymptomatic without ANY evidence of progression Or
      
                     5. 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
      
                   ≥grade 3. 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
      
              Exclusion Criteria:
      
                -  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 3.
      
                -  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
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:Male
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Overall Survival
      Time Frame:24 months
      Safety Issue:
      Description: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.

      Secondary Outcome Measures

      Measure:Disease progression
      Time Frame:24 months
      Safety Issue:
      Description:Progression will be determined by the treating physician, and may include any of the following, based on PCWG-3 and RECIST 1.1 criteria: Bone scan: Appearance of ≥ 2 new lesions on bone scan, if bone scan >12 weeks after randomisation CT/MRI: ≥ 20% increase in the sum of diameters, taking the reference as the smallest sum on study. In addition to the relative increase by 20%, the sum must also demonstrate an absolute increase >5 mm / appearance of one or more new lesions / Unequivocal progression of baseline unmeasurable lesions. initiating a new therapy for MCRPC Symptomatic-skeletal related event (SSE). Progression free survival will be measured from randomisation until the first of the following: first CT or bone scan documenting disease progression, initiation of a new therapy for MCRPC (clinical progression), or first SSE. CT Scan Progression of Non-measurable Lesions Progression will be defined based on PCWG;-3 and RECIST 1.1 as all other lesions, including
      Measure:Symptomatic Skeletal Related Events
      Time Frame:24 months
      Safety Issue:
      Description:Time to first occurrence of SSE will be defined as the time from randomisation to documentation of any of the following (whichever occurs first) + 1 day: Use of external beam radiation therapy to relieve bone pain Occurrence of new symptomatic pathological bone fractures that may be vertebral or non-vertebral. Asymptomatic compression fractures detected by radiology review only will not be considered a SSE. Spinal cord compression Change in antineoplastic therapy to treat bone pain Surgical intervention to treat bone pain Adverse event, concomitant medication, concomitant treatment, or survival follow-up CRFs and the participant's medical record will be the source of these findings and presented as categorical data.
      Measure:Analgesic/Opiate Use
      Time Frame:24 months
      Safety Issue:
      Description:Analgesic/opiate use will be assessed via Brief Pain Inventory - Short Form (BPI-SF) questionnaire and the World Health Organisation (WHO) analgesic scale, and medical record review at entry with a lead-in period (<28 days). The WHO analgesic scale will be completed every three cycles (based on medical review) and BPI-SF questionnaires will be administered every three cycles until month 24, and yearly thereafter. BPI-SF scoring:Score: 1 - 4 = Mild Pain, Score: 5 - 6 = Moderate Pain, Score: 7 - 10 = Severe Pain. WHO scoring: 1 = non-opiods (e. g. acetaminophen), 2 = as necessary, mild opiods (e. g. codeine), 3 = then strong opiods (e. g. morphine or hydromorphone) until the patient is free of pain.
      Measure:Metabolic Biomarkers
      Time Frame:24 months
      Safety Issue:
      Description:Inflammatory and cytokine systemic milieu: Serum/plasma aliquots (baseline and cycle 6) from all patient samples are intended for interrogation of a panel of markers associated with inflammation including IL1β, IL-2, IL-6, TNFα and adiponectin. Results from these investigations will be correlated with c-reactive protein and measured outcomes of exercise response and disease progression. Insulin/Glucose Metabolism: Serum aliquots (baseline and cycle 6) from all patient samples are intended for assessment of insulin levels by e.g. enzyme-linked immunosorbent assay (ELISA). Insulin sensitivity will be calculated using these fasting serum insulin values and plasma glucose determinations obtained in the additional clinical blood assessments, where the HOMA-IR method will be applied. C-peptide will also be assessed. Androgen biosynthesis: Serum aliquots from all patient samples at baseline are intended for assessment of androgen levels (Testosterone, DHT, androstenedione, DHEA, 17-hydroxy.
      Measure:Physical Function
      Time Frame:24 months
      Safety Issue:
      Description:Physical function will be assessed using strength assessments (1RM), a cardiopulmonary exercise test (CPET) and a functional performance test (400m walk). Strength assessments will be quantified in kilograms lifted, and will be dependent upon the location and size of bone metastatic lesions present as to which tests are performed (Chest Press, Leg Press, Seated Row and Leg Extension). All strength assessments should be attempted if not contraindicated. Cardiopulmonary exercise capacity will be quantified by VO2peak (L.min and mL/(kg·min)) and workload achieved (watts) during a successful CPET (RPE ≥
      Measure:Quality of Life - Patient Reported Outcome Measures
      Time Frame:24 months
      Safety Issue:
      Description:Symptoms will be considered independently of other outcome measures. Pain will be assessed via BPI-SF and medical record review at entry with a lead-in period (<28 days) and repeated measures will occur every three cycles. Changes occurring within 12 weeks of study initiation will be ignored in the absence of compelling evidence of disease progression. Response or progression of pain will be confirmed through repeat assessments separately by at least three weeks. Quality of life measured by the FACT-G, FACIT-Fatigue, QLQ-C30, EPIC-26, and EQ5D will be assessed every 3 cycles.

      Details

      Phase:N/A
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Guy's and St Thomas' NHS Foundation Trust

      Trial Keywords

      • Metastatic
      • Castrate
      • Prostate
      • Cancer
      • Resistant

      Last Updated

      August 7, 2020