Management of Oligoprogressive Castration Resistant Prostate Cancer (PCS X)

  • End date
    Nov 30, 2027
  • participants needed
  • sponsor
    Sir Mortimer B. Davis - Jewish General Hospital
Updated on 30 September 2021
antiandrogen therapy
androgen suppression
bone scan
stereotactic body radiation therapy
testosterone level
serum testosterone
medical castration
lhrh analogue
adenocarcinoma of prostate
androgen ablation


This is the first pilot phase II trial assessing the response of SBRT layered on Darolutamide (BAY1841788) on RPFS and deferring palliative second line systemic therapy in M0CRPC with oligoprogression.


Metastases-directed therapy with stereotactic body radiation therapy (SBRT) is emerging as a new treatment option for solid tumor patients with a limited number of metastases (< 5) at the time of recurrence/progression, so called oligoprogression therapy. As such, oligoprogression is defined as prostate cancer patients with castration resistance and no metastases (M0CRPC) who are receiving ADT and new generation hormonal therapy (enzalutamide, apalutamide or darolutamide) as standard of care, and who are then progressing to oligometastases. The new generation hormonal therapy used in this study will be darolutamide (ODM-201). The rationale behind this approach has been to delay the start of palliative systemic therapies that are most often toxic and associated with a negative impact on patient's quality of life, as well as being more costly. However, to date, there are no prospective published data or ongoing studies that are looking into non metastatic castration resistant prostate cancer (M0CRPC) patients who progress to oligometastases (oligoprogression). To this end, we are proposing this pilot phase II trial to assess the impact of SBRT on radiological progression-free survival (RPFS) of M0CRPC patients who are receiving darolutamide and progress to oligometastatic disease (oligoprogression).

Prostate cancer patients with castration resistance and no metastases (M0CRPC) diagnosed by bone scan and CT scan or MRI will be recruited in this phase II and initiate darolutamide while continuing on ADT (Part 1 of the study). Patients who then progress to wide spread metastases or metastases situated at locations not amenable to ablative therapy will be excluded and treated with second line therapy as per the treating physician. Patients with oligoprogression (< 5 mets) and amenable to ablative therapy will be then treated with SBRT or surgery as an ablative therapy if SBRT is not feasible (Part 2 of the study). All patients will continue to receive non-interrupted LHRH agonist, PSA testing every 6-12 weeks and re-imaging every 6 months. Imaging will also be repeated at the appearance of symptoms or at PSA progression, whichever occurs first and this schedule continues until disease progression.

This is the first pilot phase II trial assessing the response of SBRT layered on darolutamide on RPFS and deferring palliative second line systemic therapy in M0CRPC with oligoprogression. This phase II will consist of 66 M0CRPC patients treated with darolutamide, of which we anticipate 48 will be eligible for SBRT.

Condition Metastatic Prostate Cancer, Castration Resistant Prostate Cancer, Prostate Cancer Metastatic
Treatment SBRT, Darolutamide (BAY1841788)
Clinical Study IdentifierNCT04070209
SponsorSir Mortimer B. Davis - Jewish General Hospital
Last Modified on30 September 2021


Yes No Not Sure

Inclusion Criteria

Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
M0CRPC at study entry defined as follows
Ongoing androgen deprivation therapy with a LHRH agonist or bilateral orchiectomy (i.e., surgical or medical castration)
Serum testosterone level 1.7 nmol/L (50 ng/dL) at the Screening visit
PSA progression defined by a minimum of two subsequent rising PSA levels with an interval of 1 week between each determination. Patients who received an anti-androgen must have progression after withdrawal ( 4 weeks since last flutamide or 6 weeks since last bicalutamide or nilutamide). The PSA value at the Screening visit should be 2 g/L (2 ng/mL)
PSA doubling time of 10 months or less
M0 assessed by conventional imaging (CT/MRI + bone scan)
Prior cytotoxic chemotherapy for prostate cancer in adjuvant setting post radical therapy is allowed
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 or Karnofsky performance status of > 80% or higher
Estimated life expectancy of 6 months
Ability to swallow the study drug whole and comply with study
Patients should not have been previously exposed to other ARATs (Abiraterone, Enzalutamide, Apalutamide)
Inclusion Criteria (Part 2)
metastatic sites (on conventional imaging)
tumors within any given organ system, excluding brain (e.g. up to 4 bone metastases, or 4 lung metastases)
All sites of disease must be amenable to SBRT with no history of the metastases being irradiated (radiation exposure prior to the development of the metastases is permitted as long as the radiation exposure was not intended for the metastases. For example, if there is prior pelvic radiation to the prostate and a subsequent iliac metastasis develops within the previously irradiated pelvic radiation field, then the iliac metastasis would be eligible per the institution policy and practice)
In the case of a suspicious lesion in an unusual location such as lung or thoracic lymph nodes (without other abdominal lymph nodes), a confirmatory imaging or biopsy is strongly recommended

Exclusion Criteria

Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment
Presence of distant metastasis, including previously treated (clinical stage M1) is exclusive, however isolated pelvic nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion criteria
History of another malignancy within the previous 5 years other than curatively treated non-melanoma skin cancer
Absolute neutrophil count < 1,500/L, platelet count < 100,000/L, or hemoglobin < 5.6 mmol/L (9 g/dL) at the Screening visit (NOTE: patients may not have received any growth factors within 7 days or blood transfusions within 28 days of the hematologic laboratory values obtained at the Screening visit)
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal and total bilirubin > 1.5 times the upper limit of normal at the Screening visit
Creatinine > 2 times the upper limit of normal at the Screening visit
Clinically significant cardiovascular disease including
Stroke or myocardial infarction within 6 months
Uncontrolled angina within 6 months
Coronary/peripheral artery bypass graft within 6 months
Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan performed within three months results in a left ventricular ejection fraction that is 45%
History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
Uncontrolled hypertension as indicated by a resting systolic BP 160 mmHg or diastolic BP 100 mmHg at screening. Patients may be re-screened after adjustments of antihypertensive medications
Bradycardia as indicated by a heart rate of < 50 beats per minute on the Screening ECG
Gastrointestinal disorder or procedure which expects to interfere significantly with absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months)
Major surgery within 4 weeks of enrollment (Day 1 Visit)
Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease
Use of opiate analgesics (eg. morphine, fentanyl, etc.) for pain from prostate cancer within 4 weeks of enrollment (Day 1 visit). This does not apply to non-morphine drugs like codeine
Radiation therapy for treatment of the primary tumor within 3 weeks of enrollment (Day 1 visit)
Radiation or radionuclide therapy for treatment of metastasis
Primary disease not treated
Hormone nave prostate cancer patients
Treatment with estrogens or AR inhibitors (bicalutamide, flutamide, nilutamide, cyproterone acetate) within 4 weeks of enrollment (Day 1 visit)
Treatment with systemic biologic therapy for prostate cancer (other than approved bone targeted agents and GnRH-analogue therapy) or other agents with anti-tumour activity within 4 weeks of enrollment (Day 1 visit)
Prior use of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, enzalutamide, Apalutamide, TAK-700, TAK-683, TAK-448) or targets the androgen receptor (e.g., BMS 641988) on clinical trials
Participation in a previous clinical trial of darolutamide, where the patient has received darolutamide. If patient has received placebo and it is known, this may not apply
Known or suspected contraindications or hypersensitivity to darolutamide or GnRH agonists or any of the components of the formulations
Use of an investigational agent within 4 weeks of enrollment (Day 1 visit)
Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within four weeks of enrollment (Day 1 visit)
Any condition or reason that, in the opinion of the Investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data
Unable to swallow study medications and comply with study requirements
Exclusion criteria (Part 2)
Known or suspected brain metastasis or active leptomeningeal disease
> 5 metastasis
More than 4 metastasis in the same organ
Patients considered for SBRT in previous history of radiation therapy to the same area
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