Prostatic Neoplasms, Castration-Resistant
Conditions
Keywords
Fractionated stereotactic radiotherapy, second-generation antiandrogen, Phase II, castration-resistant prostate cancer, oligometastatic patients
Brief summary
The objectives of the study are to analyze the results obtained in survival, safety and quality of life after the combination of SBRT plus second-generation antiandrogen in patients diagnosed with metastatic castration-resistant prostate cancer in oligometastasis (≤5). Hence, the investigators evaluate the results of the combination of two widely used treatments in prostate cancer: SBRT plus the 'standard of care' for patients with mCRPC, second-generation antiandrogens (abiraterone and enzalutamide). Primary objective: Determine the PRFS measured from the time of initiation of second-generation antiandrogen to the time of radiological progression by choline PET/CT or 68Ga-PSMA PET/CT, in patients with mCRPC treated with the combination of second-generation antiandrogen plus SBRT. Secondary objectives: * Overall survival (time from initiation of second-generation antiandrogen to exitus) in patients with mCRPC treated with the combination of second-generation antiandrogen plus SBRT. * Quality of life of these patients using the European Organization for Research and Treatment of Cancer (EORTC) quality of life scale, EORTC QLQ-C30, validated for oncology patients. * Acute and chronic toxicity according to the "Common Terminology Criteria for Adverse Events" (CTCAEv5.0) scale. This is a phase II, multicenter, prospective, single group study in patients with castrate-resistant prostate cancer (CRPC). Patients will be recruited at the participant sites, after study approval and hospital authorization. 51 patients will be included in the study. Eligible patients will require: * Choline PET/CT or 68Ga-PSMA PET/CT, dated no more than 8 weeks prior to inclusion. * Clinical history, physical examination and functional evaluation scale (ECOG). * Geriatric assessment scale for patients \> 75 years (modified G8 scale) * Toxicity scale assessment (CTCAEv5.0) * Baseline quality of life questionnaire (EORTC QLQ-C30) (47) * Blood tests with complete blood count, coagulation, liver function, renal function, ions, alkaline phosphatase, PSA and total and free testosterone, dated no more than 4 weeks prior inclusion. * Inclusion/exclusion criteria assessment * Second generation antiandrogen prescription, chosen by the responsible physician according to clinical practice, in each case. Each patient will be included in the study once the second generation antiandrogen is initiated (which will be maintained until radiological progression, suspension due to poor tolerance and/or exitus). SBRT will be performed at least 2 weeks after initiating treatment with second generation antiandrogen, without exceeding 8 weeks from the start of treatment, and follow-up will continue up to a maximum of 36 months after completion of SBRT and/or exitus. Recruitment time is estimated at 36 months and a total follow-up time of 36 months. The total duration of the trial is therefore expected to be 6 years, to allow complete follow-up of the last patients included.
Interventions
DRUGXtandi
Each patient will be included in the study once the second generation antiandrogen is initiated (which will be maintained until radiological progression, suspension due to poor tolerance and/or exitus)
Each patient will be included in the study once the second generation antiandrogen is initiated (which will be maintained until radiological progression, suspension due to poor tolerance and/or exitus)
RADIATIONSBRT
SBRT will be performed at least 2 weeks after initiating treatment with second generation antiandrogen, without exceeding 8 weeks from the start of treatment, and follow-up will continue up to a maximum of 36 months after completion of SBRT and/or exitus
Sponsors
Instituto de Investigación en Oncología Radioterápica - Fundación Española de Oncología Radioterápic
Fundacion Miguel Servet
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Each patient will be included in the study once the second generation antiandrogen is initiated (which will be maintained until radiological progression, suspension due to poor tolerance and/or exitus). SBRT will be performed at least 2 weeks after initiating treatment with second generation antiandrogen, without exceeding 8 weeks from the start of treatment, and follow-up will continue up to a maximum of 36 months after completion of SBRT and/or exitus
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
* Patients with histologically prostate adenocarcinoma, confirmed with a biopsy. * Testosterone in biochemical castration ranges (testosterone \<50 ng/ml or 1.7 nmol/L) and documented progression: biochemical according to Phoenix criteria or distant by radiological confirmation (PSMA PET/CT or Choline PET/CT) * Biochemistry progression confirmed according to Phoenix criteria, with testosterone in castration levels (testosterone \<50 ng/ml or 1.7 nmol/L). * Radiological confirmation (with choline-PET/CT or 68Ga-PSMA-PET/CT) of ≤5 node or bone metastasis, non-visceral, eligible to receive SBRT treatment (\< 3 cm major diameter in bone metastases, \< 5 cm in lymph node metastases). In the case of very close metastases, a limit of up to 5 treatment fields with SBRT is allowed, instead of 5 metastases. * Patients candidate to receive treatment with abiraterone or enzalutamide as per clinical routine, and treatment selection and prescription assigned by responsible physician before the inclusion in the study. or or who has started treatment no more than 14 days prior to signing, as first-line treatment after a diagnosis of oligoresistance. * Patients must provide written informed consent. * Life expectancy \> 3 months.
Exclusion criteria
* Patients with prostate carcinoma with histology other than adenocarcinoma. * No previous biopsy. * \> 5 metastasis, not approachables in 5 treatment fields * Patients with visceral metastasis and or metastasis non elegible to receive SBRT. * Patients with Testosterone above castration levels * Patients with prior treatment with docetaxel as first-line CRPC treatment (previous docetaxel treatment is permitted when administered as hormone-sensitive metastatic prostate cancer treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the PRFS | From the start of the study (the day it begins) or up to 14 days before the start of the study (corresponding to the start of treatment with second-generation antiandrogens) until the time of radiological progression during follow-up, it can be up to 36. | Determine the PRFS measured from the time of initiation of second-generation antiandrogen to the time of radiological progression by choline PET/CT or 68Ga-PSMA PET/CT, in patients with mCRPC treated with the combination of second-generation antiandrogen |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | From the start of second-generation antiandrogen therapy (at baseline or up to 14 days prior) to the date of death from any cause, assessed up to 36 months. | Overall survival (time from initiation of second-generation antiandrogen to exitus) in patients with mCRPC treated with the combination of second-generation antiandrogen plus SBRT. |
| Quality of life by EORTC scale | from recruitment to the end of patient follow-up (up to 36 months) | QoL using the European Organization for Research and Treatment of Cancer (EORTC) quality of life scale, EORTC QLQ-C30, validated for oncology patients. The scale converts all scores to a standardized range from 0 (minimum) to 100 (maximum). A high score indicates a better outcome (high quality of life and good health). |
| Acute and chronic toxicity | from recruitment to the end of patient follow-up (up to 36 months) | Acute and chronic toxicity according to the "Common Terminology Criteria for Adverse Events" (CTCAEv5.0) scale |
Countries
Spain
Contacts
CONTACTPablo Raña Diez, PhD
CONTACTCristina Gutierrez Povedano, PhD
PRINCIPAL_INVESTIGATORMarta Barrado Los Arcos, MD
Hospital of Navarra
Outcome results
None listed