Rate of PSA Response in Oligometastatic,CRPC Undergoing SBRT in Combination With Abiraterone Acetate (AA), Compared to Patients Treated With AA Alone Clinical Trial
Official title:
A 2 Arm, Phase II Controlled Randomized Trial Comparing Efficacy and Safety of Abiraterone and Abiraterone Associated With of Ablative Radiation Therapy in Patients With Oligometastatic Castration Resistant Prostate Cancer (ARTO Trial)
Metastatic castration resistant prostate cancer causes approximately 258400 deaths annually
worldwide.
In the presence of metastatic disease, systemic treatment remains the main clinical option.
However, since the introduction of highly sensitive imaging techniques, a new clinical entity
of metastatic patients with a limited number of lesions has been defined: oligometastatic
patients.
Although a clear benefit has yet to be demonstrated in this group of patients, the use of
stereotactic body radiotherapy (SBRT) or other local therapies directed against all active
lesions has been suggested as a possible salvage treatment.
Irradiation of metastatic foci may delay the emergence of castration resistance because
irradiation is effective against both ADT¬ sensitive and ADT ¬resistant prostate cancer cells
as shown in re-biopsy studies. Stereotactic body radiation therapy has been used in this
setting to defer the initiation of ADT in patients with oligometastatic prostate cancer with
notable results.
Abiraterone acetate is a first class inhibitor of cytochrome P ¬450c17, a critical enzyme in
extragonadal and testicular androgen synthesis. Abiraterone plus low dose prednisone improves
survival in patients with metastatic castration ¬resistant prostate cancer who have already
received docetaxel and the combination therapy has received regulatory approval for this
indication. Furthermore, Abiraterone acetate is approved also in patients who did not undergo
to docetaxel chemotherapy, after the results from the COU-AA 302 study; Results from this
phase III trial confirmed the benefit in chemo-naïve patients treated with abiraterone
acetate both in terms of overall and radiological progression free survival, if compared to
placebo.
In oligometastatic CRPC, the rationale to use SBRT is that the addition of a local ablative
treatment could improve disease control in mCRPC patients treated with a systemic therapy.
The current phase II randomized trial,"Ablative Radiation Therapy in patients with
Oligometastatic castration resistant prostate cancer (ARTO trial)" aims to evaluate the
difference in PSA response rate between the experimental arm (AA+SBRT) and control arm (AA)
in metastatic castration-resistant prostate cancer patients
This phase II randomized trial was designed to evaluate the difference in PSA response rate
between the experimental arm (AA+SBRT) and control arm (AA). PSA response will be defined as
a post-treatment decrease > 50% from baseline measured within 6 months.
Study design
This is a phase II randomized multicenter study in patients affected by oligo ¬mCRPC, treated
with standard of care (GnRH agonist or antagonist plus abiraterone acetate and prednisone)
and randomized to receive SBRT to all sites of disease. Patients will be randomly assigned in
a 1:1 ratio to both treatment, stratified by Centre, Performance Status, and number of
metastases.
Randomization will be performed the same day of the baseline evaluation (+/-3 days).
Planned size of the overall study population is 174 patients, 87 for each arm. The study will
include a screening phase and a treatment phase.
The screening phase allows for assessment of subject eligibility, demographics, PSA,
testosterone, comorbidities and current drug therapies up to 45 days prior to randomization.
The treatment phase consists of systemic treatment with abiraterone acetate 1000 mg daily and
prednisone 10 mg daily, plus GnRH agonist or antagonist (control arm). Furthermore, the
patients in the experimental arm will receive SBRT to all metastatic lesions.
SBRT will be delivered in 1 to 5 fractions, and the dose and fractionation schedule will
depend on the size and location of the lesion and the surrounding normal tissue constraints
in accordance with AAPM Task Group 101 recommendations [19]. Considering an Alfa/beta of 3, a
BED3 > 100 Gy is recommended. The total planned duration of the study is 40 months,
consisting in 28 months enrollment period, during which patients will perform the screening
and will begin standard of care treatment with or without SBRT and later phase of 12 months
in which patients will continue the treatment with standard of care and will be submitted to
periodic checks every 3 months.
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