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

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ClinicalTrials.gov Identifier: NCT03449719
Recruitment Status : Not yet recruiting
First Posted : February 28, 2018
Last Update Posted : February 28, 2018
Sponsor:
Information provided by (Responsible Party):
Lorenzo Livi, Azienda Ospedaliero-Universitaria Careggi

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


Condition or disease Intervention/treatment Phase
Rate of PSA Response in Oligometastatic,CRPC Undergoing SBRT in Combination With Abiraterone Acetate (AA), Compared to Patients Treated With AA Alone Radiation: SBRT - Ablative radiation Therapy Drug: Abiraterone Acetate Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 174 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
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)
Estimated Study Start Date : May 1, 2018
Estimated Primary Completion Date : September 1, 2021
Estimated Study Completion Date : May 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Active Comparator: 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).
Drug: Abiraterone Acetate
systemic treatment with abiraterone acetate 1000 mg daily and prednisone 10 mg daily, plus GnRH agonist or antagonist
Other Name: AA

Experimental: 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

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.
Other Name: AA+SBRT

Drug: Abiraterone Acetate
systemic treatment with abiraterone acetate 1000 mg daily and prednisone 10 mg daily, plus GnRH agonist or antagonist
Other Name: AA




Primary Outcome Measures :
  1. rate PSA [ Time Frame: within 6 months ]
    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.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Male with metastatic castration resistant prostate cancer
Accepts Healthy Volunteers:   No
Criteria

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)


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03449719


Contacts
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Contact: Lorenzo Livi, Prof 055 7947264 lorenzo.livi@unifi.it

Sponsors and Collaborators
Lorenzo Livi
Investigators
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Principal Investigator: Lorenzo Livi, Prof Radioterapia Oncologica AOUC
  Study Documents (Full-Text)

Documents provided by Lorenzo Livi, Azienda Ospedaliero-Universitaria Careggi:
Study Protocol  [PDF] September 26, 2017

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Responsible Party: Lorenzo Livi, Prof, Azienda Ospedaliero-Universitaria Careggi
ClinicalTrials.gov Identifier: NCT03449719    
Other Study ID Numbers: ARTO
First Posted: February 28, 2018    Key Record Dates
Last Update Posted: February 28, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Abiraterone Acetate
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 Enzyme Inhibitors