Castration-resistant Prostate Cancer, Metastatic Prostate Cancer
Conditions
Brief summary
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.
Detailed description
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), if not receiving darolutamide prior to study entry already. 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.
Interventions
Darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg.
RADIATIONSBRT
SBRT will consist of 2-5 fractions of highly targeted radiation therapy delivered every other day. The radiation component will be completed in 4-10 days.
Sponsors
Sir Mortimer B. Davis - Jewish General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(Part 1): * Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features; * M0CRPC at study entry defined as follows: 1. Ongoing androgen deprivation therapy with a LHRH agonist or bilateral orchiectomy (i.e., surgical or medical castration); 2. Serum testosterone level ≤ 1.7 nmol/L (50 ng/dL) at the Screening visit; 3. 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 μg/L (2 ng/mL) 4. PSA doubling time of 10 months or less, 5. M0 assessed by conventional imaging (CT/MRI + bone scan). NOTE: If darolutamide started prior to study entry, evidence of inclusion criteria 1-5 listed above prior to start of darolutamide must be submitted to determine study eligibility * 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): * ≤ 5 metastatic sites (on conventional imaging); * ≤ 4 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
(Part 1): * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Progression-free Survival | 5 years | Time from first day of SBRT until confirmed second radiological progression or start of new antineoplastic therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional Assessment of Cancer Therapy-Prostate | 5 years | Evaluate the impact of the treatment on the patient's quality of life using the FACT-P questionnaire |
| Quality of Life - Fatigue | 5 years | Evaluate the impact of the treatment on the patient's quality of life using the Brief Fatigue Inventory (BFI) questionnaire |
| Quality of Life - Pain | 5 years | Evaluate the impact of the treatment on the patient's quality of life using the Brief Pain Inventory (BPI) questionnaire |
| Toxicity of ODM-201 | 5 years | To determine acute and late toxicity due to ODM-201, scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
| Time to Subsequent Systemic Antineoplastic Therapy | 5 years | Time to the administration of subsequent antineoplastic systemic therapy |
| PSA response | 5 years | PSA value and onset of biochemical failure will be recorded |
| Overall Survival | 5 years | Time from randomization until death from any cause |
| Disease Specific Survival | 5 years | Time from randomization until death due to prostate cancer |
| Time to Skeletal-related Event (SRE) | 5 years | Date of first SRE will be recorded |
| Local Control | 5 years | To evaluate the impact of SBRT on oligometastases progression by radiographic imaging or the start of new antineoplastic therapy. |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORTamim Niazi, MD
Jewish General Hospital
Outcome results
None listed