Rate of PSA Response in Oligometastatic,CRPC Undergoing SBRT in Combination With Abiraterone Acetate (AA), Compared to Patients Treated With AA AloneARTONCT03449719

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

A study testing SBRT - Ablative radiation Therapy and Abiraterone Acetate in people with Rate of PSA Response in Oligometastatic,CRPC Undergoing SBRT in Combination With Abiraterone Acetate (AA), Compared to Patients Treated With AA Alone, run by Lorenzo Livi.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial 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. Read more about this study

Who is it for?: Any age, men only
Conditions the study is for: Rate of PSA Response in Oligometastatic,CRPC Undergoing SBRT in Combination With Abiraterone Acetate (AA), Compared to Patients Treated With AA Alone
What is being tested?: SBRT - Ablative radiation Therapy and Abiraterone Acetate
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 174 participants
Where: No sites listed yet
Study dates: 1 May 2018to 1 May 2022
Phase: Interventional

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
Men only
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Each potential subject must satisfy all of the following criteria to be enrolled in the study.
Metastatic disease and only <3 metastatic sites recorded (irrespective if nodal or bone).
Patients should have received abiraterone acetate for 30 days before eventual start of radiotherapy in the experimental arm (+/- 3 days)
Asymptomatic or mildly symptomatic patients according to clinical judgement.
Age ≥ 18 years.
Subject must have signed an informed consent document indicating that they understand the purpose of procedures required for the study and are willing to participate in the study

Who cannot join

1. More than 3 metastatic lesions.
2. Visceral involvement.
3. Known or suspected contraindications or hypersensitivity to Abiraterone, GnRH agonist/antagonist or Radiotherapy.
4. Comorbidities that contraindicate Abiraterone, GnRH agonist/antagonist or Radiotherapy.
5. Any condition for which, in the option of the investigator, participation would not be in the best interest of subject.
6. Patients who received previous therapies for mCRPC (excluded hormonal therapy)

Trial locations and contacts

No sites are listed yet.

Lorenzo Livi, Prof contact

055 7947264

lorenzo.livi@unifi.it

About this study

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

Read the 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
Being tested: SBRT - Ablative radiation Therapy, Abiraterone Acetate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SBRT - Ablative radiation TherapyRadiation
Also called AA+SBRT
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.
Abiraterone AcetateDrug
Also called AA
systemic treatment with abiraterone acetate 1000 mg daily and prednisone 10 mg daily, plus GnRH agonist or antagonist

Study groups in NCT03449719
Study group	Role	What they receive
Abiraterone	Active comparator	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). Receives: Drug: Abiraterone Acetate
Abiraterone associated withAblative Radiation	Experimental	the patients in the experimental arm will receive SBRT to all metastatic lesions, concomitantly with abiraterone acetate. 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. Considering an Alfa/beta of 3, a BED3 > 100 Gy is recommended Receives: Radiation: SBRT - Ablative radiation Therapy; Drug: Abiraterone Acetate

What is being measured

The primary outcome is the main question the study is designed to answer.

rate PSA
rate of PSA response in nodal and/or bone oligometastatic (⩽3 lesions), castration resistant prostate cancer patients undergoing SBRT in combination with AA (experimental arm), compared to patients treated with AA (control arm). PSA response will be defined as a post-treatment decrease > 50% from baseline measured within 6 months.
Measured: within 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 May 20181 May 2022

First posted28 Feb 2018
Study start1 May 2018 (estimated)
Primary completion1 Sep 2021 (estimated)
Study completion1 May 2022 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Rate of PSA Response in Oligometastatic,CRPC Undergoing SBRT in Combination With Abiraterone Acetate (AA), Compared to Patients Treated With AA AloneStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: A Phase II study is suitable to investigate the interaction of systemic therapy (ADT and abiraterone) with locoregional therapy (SBRT). The duration of the study equal to 40 months was defined taking into account both the expected time of occurrence of investigated endpoints and feasibility considerations related to patient availability.
Masking: None (open label)
Enrolment: 174 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03449719
Sponsor's protocol ID: ARTO
Acronym: ARTO
Status last verified: Feb 2018
First submitted: 22 Feb 2018
Last updated: 28 Feb 2018
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Francolini G, Di Cataldo V, Caini S, Garlatti P, Aquilano M, Bertini N, Bruni A, Ingrosso G, D'Angelillo RM, Tagliaferri L, Jereczek-Fossa BA, Augugliaro M, Triggiani L, Parisi S, Masieri L, Campi R, Valicenti RK, Simontacchi G, Greto D, Bonomo P, Loi M, Tang C, Livi L; ARTO Working Group. SBRT plus abiraterone acetate and ADT versus abiraterone acetate and ADT in oligometastatic castrate-resistant prostate cancer (ARTO): long-term, unplanned overall survival analysis of an open-label, randomised, phase 2 trial. Lancet Oncol. 2026 Jul;27(7):830-838. doi: 10.1016/S1470-2045(26)00178-6.
PubMed 42372744
Francolini G, Allegra AG, Detti B, Di Cataldo V, Caini S, Bruni A, Ingrosso G, D'Angelillo RM, Alitto AR, Augugliaro M, Triggiani L, Parisi S, Facchini G, Banini M, Simontacchi G, Desideri I, Meattini I, Valicenti RK, Livi L; ARTO Working Group members. Stereotactic Body Radiation Therapy and Abiraterone Acetate for Patients Affected by Oligometastatic Castrate-Resistant Prostate Cancer: A Randomized Phase II Trial (ARTO). J Clin Oncol. 2023 Dec 20;41(36):5561-5568. doi: 10.1200/JCO.23.00985. Epub 2023 Sep 21.
PubMed 37733977
Francolini G, Di Cataldo V, Detti B, Simontacchi G, Loi M, Valzano M, Desideri I, Meattini I, Mangoni M, Livi L. Killing two birds with a stone: how to maximise benefit from metastasis-directed therapy and modern systemic treatment in oligometastatic hormone sensitive prostate cancer. Clin Exp Metastasis. 2022 Dec;39(6):841-843. doi: 10.1007/s10585-022-10187-2. Epub 2022 Oct 15.
PubMed 36242700
Francolini G, Loi M, Detti B, Desideri I, Mangoni M, Simontacchi G, Meattini I, Livi L. Integrating stereotactic body radiation therapy (SBRT) and systemic treatments in oligoprogressive prostate cancer: new evidence from the literature. Clin Exp Metastasis. 2021 Apr;38(2):227-230. doi: 10.1007/s10585-021-10072-4. Epub 2021 Jan 20.
PubMed 33471291