NCT03449719

Phase II Randomized Trial of Radiation Therapy in Oligometastatic mCRPC Prostate Cancer (ARTO)

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)

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 174 (estimated)
• Sponsor: Lorenzo Livi · Academic / Other
• Sex: Male
• Age: —
• Healthy volunteers: Not accepted

Summary

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

Detailed description

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.

Conditions

• Rate of PSA Response in Oligometastatic,CRPC Undergoing SBRT in Combination With Abiraterone Acetate (AA), Compared to Patients Treated With AA Alone

Interventions

Type	Name	Description
RADIATION	SBRT - Ablative radiation 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.
DRUG	Abiraterone Acetate	systemic treatment with abiraterone acetate 1000 mg daily and prednisone 10 mg daily, plus GnRH agonist or antagonist

Timeline

• Start date: 2018-05-01
• Primary completion: 2021-09-01
• Completion: 2022-05-01
• First posted: 2018-02-28
• Last updated: 2018-02-28