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

NCT ID: NCT03449719

Last Updated: 2018-02-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

174 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-01

Study Completion Date

2022-05-01

Brief Summary

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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

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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

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Abiraterone

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).

Group Type ACTIVE_COMPARATOR

Abiraterone Acetate

Intervention Type DRUG

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

Abiraterone associated withAblative Radiation

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

Group Type EXPERIMENTAL

SBRT - Ablative radiation Therapy

Intervention Type 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.

Abiraterone Acetate

Intervention Type DRUG

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

Interventions

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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.

Intervention Type RADIATION

Abiraterone Acetate

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

Intervention Type DRUG

Other Intervention Names

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AA+SBRT AA

Eligibility Criteria

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Inclusion Criteria

* Each potential subject must satisfy all of the following criteria to be enrolled in the study.

1. Metastatic disease and only \<3 metastatic sites recorded (irrespective if nodal or bone).
2. Patients should have received abiraterone acetate for 30 days before eventual start of radiotherapy in the experimental arm (+/- 3 days)
3. Asymptomatic or mildly symptomatic patients according to clinical judgement.
4. Age ≥ 18 years.
5. 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

Exclusion Criteria

* 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)
Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Lorenzo Livi

OTHER

Sponsor Role lead

Responsible Party

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Lorenzo Livi

Prof

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Lorenzo Livi, Prof

Role: PRINCIPAL_INVESTIGATOR

Radioterapia Oncologica AOUC

Central Contacts

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Lorenzo Livi, Prof

Role: CONTACT

Phone: 055 7947264

Email: [email protected]

References

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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.

Reference Type DERIVED
PMID: 37733977 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36242700 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33471291 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Other Identifiers

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ARTO

Identifier Type: -

Identifier Source: org_study_id