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

NCT03449719 | Unknown

• 1 other identifier: ARTO
• Study Type: interventional
• Target: 174
• Locations: 0 countries
• Sites: N/A

Brief 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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  within 6 months

Study Arms (2)

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).

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

Radiation: SBRT - Ablative radiation Therapy; Drug: Abiraterone Acetate

Interventions

SBRT - Ablative radiation Therapy RADIATION

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.

Also known as: AA+SBRT

Abiraterone associated withAblative Radiation

Abiraterone Acetate DRUG

systemic treatment with abiraterone acetate 1000 mg daily and prednisone 10 mg daily, plus GnRH agonist or antagonist

Also known as: AA

Abiraterone; Abiraterone associated withAblative Radiation

Eligibility Criteria

• Gender Eligibility Details: Male with metastatic castration resistant prostate cancer
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Lorenzo Livi: lead

Related Publications (3)

• 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.

  PMID: 37733977 DERIVED

• 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.

  PMID: 36242700 DERIVED

• 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.

  PMID: 33471291 DERIVED

MeSH Terms

Interventions

Abiraterone Acetate

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Lorenzo Livi, Prof

  Radioterapia Oncologica AOUC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lorenzo Livi, Prof

CONTACT

055 7947264; lorenzo.livi@unifi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof

Model Details: 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.

Study Record Dates

• First Submitted: February 22, 2018
• First Posted: February 28, 2018
• Study Start: May 1, 2018
• Primary Completion: September 1, 2021
• Study Completion: May 1, 2022
• Last Updated: February 28, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share