Stereotactic Body Radiation for Prostate Oligometastases (ORIOLE)

Phase II Randomized Observation Versus Stereotactic Ablative RadiatIOn for OLigometastatic Prostate CancEr (ORIOLE) Trial

Men with oligometastatic prostate cancer lesions will be randomized (1:2) to observation versus SBRT. The study will NOT be blinded. Within three weeks of the initial treatment planning, SBRT (1-5 fractions) will be administered.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer; Oligometastases
• Intervention / Treatment: Radiation: SBRT

Detailed Description

This research is being done to determine if we can improve the outcome of prostate cancer patients who have failed primary treatment - surgery or local radiation to the prostate - and have 3 or fewer bone metastases. Patients with metastatic prostate cancer disease will usually be placed on hormonal therapy which can work well for a period of time, but hormonal therapy can have side effects that greatly trouble men. Any effort to delay the start of hormonal therapy would be an advantage to the patient. Radiation treatment usually takes many weeks to deliver and is not given in a high enough doses to metastases to prevent them from coming back locally. Stereotactic body radiation therapy (SBRT) is highly focused radiation, given in a very dose intensive fashion and delivered in usually less than one week. Stereotactic body radiation has been shown to be very effective on bone metastases. Therefore, we are studying the effects of stereotactic body radiation treatment on patients with five or fewer prostate cancer bone metastases to determine if we can stall the use of hormonal therapy and/or prevent other bone metastases from developing elsewhere in the body.

Additionally, fundamental analysis of the oligometastatic state with be achieved through correlation with investigational DCFPyL-positron emission tomography (PET) imaging, which can help us find cancer that has spread (metastatic disease) from its original site in people who have cancer in their prostate to other parts of their body.

Specifically, 54 men with biochemically recurrent, oligometastatic prostate adenocarcinoma will be accrued across 3 centers in the United States. Patients were stratified by primary intervention (surgery vs radiotherapy), prior hormonal therapy, and PSA doubling time, then randomized 2:1 to SBRT or observation. The primary clinical endpoint is progression at 6 months from randomization with the hypothesis that SBRT to all metastases will forestall progression by disrupting the metastatic process. Secondary clinical endpoints include local control at 6 months post-SBRT, SBRT-associated toxicity and quality of life, and ADT-free survival (ADT-FS).

Alterations in the biology of the oligometastatic state induced by stereotactic ablative radiotherapy (SABR) will be investigated using leading-edge correlatives, including: analysis of circulating tumor cells (CTCs; Epic Sciences, San Diego, CA), deep sequencing of circulating tumor DNA (ctDNA) using Cancer Personalized Profiling by deep sequencing (CAPP-Seq) to non-invasively assess tumor burden, and ImmunoSEQ profiling of T-cell repertoires to elucidate the immunological response to SABR (Adaptive Technologies, Seattle, WA). Lastly, the use of the Color Genomics platform (Burlingame, CA), a hereditary cancer assay assessing pathogenic mutations in 30 cancer predisposition genes that account for >90% of the germline mutations known to occur in men with castrate resistant metastatic prostate cancer (mCRPC), will help inform and allow for efforts to advance a more personalized medicine approach to tailor screening and therapies in these men.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Patient must have at least one and up to three asymptomatic metastatic tumor(s) of the bone or soft tissue develop within the past 6-months that are ≤ 5.0 cm or <250 cm3.
• Patient must have had their primary tumor treated with surgery and/or radiation.
• Histologic confirmation of malignancy (primary or metastatic tumor).
• PSADT <15 months. PSA doubling time (PSADT) will be calculated using as many PSA values that are available from time of relapse (PSA > 0.2). To calculate PSADT, the Memorial Sloan Kettering Cancer Center Prostate Cancer

Prediction Tool will be used. It can be found at the following web site:

https://www.mskcc.org/nomograms/prostate/psa-doubling-time.

• Patient may have had prior systemic therapy and/or ADT associated with treatment of their primary prostate cancer. Patient may have had ADT associated with salvage radiation therapy (to the primary prostate cancer or pelvis is allowed).
• PSA >1 but <50.
• Testosterone > 125 ng/dL.
• Patient must have a life expectancy ≥ 12 months.
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Patient must have normal organ and marrow function as defined as:

Leukocytes >2,000/μL Absolute Neutrophil Count >1,000/μL Platelets >50,000/μL

- Patient must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• No more than 3 years of ADT is allowed, with the most recent ADT treatment having occurred greater than 6 months prior to enrollment.
• DCFPyL-PET/MRI or DCFPyL-PET/CT scan within the past 6 months with results that demonstrate more disease lesions than baseline CT/Bone Scan
• Castration-resistant prostate cancer (CRPC).
• Suspected pulmonary and/or liver metastases (greater >10 mm in largest axis).
• Patient receiving any other investigational agents.
• Patient is participating in a concurrent treatment protocol.
• Total bilirubin > 3 times the upper limit of normal.
• Liver Transaminases > 5-times the upper limit of normal.
• Unable to lie flat during or tolerate PET/MRI, PET/CT or SBRT.
• Liver Transaminases > 5-times the upper limit of normal.
• Prior salvage treatment to the primary prostate cancer or pelvis is allowed.
• Refusal to sign informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Observational (no SBRT); Men with oligometastatic prostate cancer lesions randomized to observation
EXPERIMENTAL: SBRT; Men with oligometastatic prostate cancer lesions randomized to stereotactic body radiation therapy (SBRT).	Radiation: SBRT; SBRT (1-5 fractions) will be administered.; Other Names: Stereotactic Body Radiation; Stereotactic Ablative Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression at 6 Months	Number of participants who progressed at 6 months. Progression is defined as either: 1) a ≥ 25% increase in PSA from nadir (and by ≥ 2 ng/mL), requiring confirmation ≥ 4 weeks later (PCWG2 criteria); and/or, 2) clinical/radiographic-progression defined as symptomatic progression (worsening disease-related symptoms or new cancer-related complications), or radiologic progression (on CT scan: ≥ 20% enlargement in sum diameter of soft-tissue target lesions [RECIST1.1 criteria]; on bone scan: ≥ 1 new bone lesions),initiation of ADT or death due to any cause, whichever occurs first.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Local Progression	Number of months until local progression in patients with oligometastatic disease.	up to 6 months
Local Control of SBRT Group	Number of lesions that did not increase in size by at least 20% or more on CT from baseline to 6 months.	6 months
Toxicity as Assessed by Number of Participants With Adverse Events Grade 3 or Higher	Number of participants experiencing adverse events Grade 3 or higher, as defined by CTCAE.	up to 6 months
Toxicity as Assessed by Number of Participants With Adverse Events Grades 1 or 2	Number of participants experiencing adverse events Grades 1 or 2, as defined by CTCAE	up to 6 months
Change in Quality of Life as Assessed by Brief Pain Inventory	We will assess quality of life following completion of Stereotactic Body Radiation Therapy via Brief Pain Inventory questionnaire made up of 9 questions. Each question scores from 0-10, with higher scores mean worse outcome or more pain. An overall score, calculated by adding the scores for questions 2, 3, 4 and 5 and then dividing by 4, will be calculated pre-treatment and at the time of day 180. The change in score (between baseline and 6 months) will be evaluated.	Baseline and 6 months
Change of DCFPyL-PET/MRI Positive Lesions	18F-DCFPyL Positron Emission Tomography (PET)/MRI or -PET/CT positive sites that are positive for new or progressive metastatic disease by bone scan/CT at 6-months following SBRT.	6 months
Change in Survival of Two Groups as Assessed by PSA Level	The PSA levels in blood will be measured in units of nanograms per milliliter (ng/mL).	Baseline and 6 months
Androgen Deprivation Therapy-free Survival	Androgen Deprivation Therapy-free survival will be assessed using the number of participants deceased at 6 months.	6 month

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Phuoc Tran, M.D., Johns Hopkins Department of Radiation Oncology and Molecular Radiation Sciences

Publications and helpful links

General Publications

• Phillips R, Shi WY, Deek M, Radwan N, Lim SJ, Antonarakis ES, Rowe SP, Ross AE, Gorin MA, Deville C, Greco SC, Wang H, Denmeade SR, Paller CJ, Dipasquale S, DeWeese TL, Song DY, Wang H, Carducci MA, Pienta KJ, Pomper MG, Dicker AP, Eisenberger MA, Alizadeh AA, Diehn M, Tran PT. Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial. JAMA Oncol. 2020 May 1;6(5):650-659. doi: 10.1001/jamaoncol.2020.0147.
• Radwan N, Phillips R, Ross A, Rowe SP, Gorin MA, Antonarakis ES, Deville C, Greco S, Denmeade S, Paller C, Song DY, Diehn M, Wang H, Carducci M, Pienta KJ, Pomper MG, DeWeese TL, Dicker A, Eisenberger M, Tran PT. A phase II randomized trial of Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr (ORIOLE). BMC Cancer. 2017 Jun 29;17(1):453. doi: 10.1186/s12885-017-3455-6.
• Deek MP, Van der Eecken K, Sutera P, Deek RA, Fonteyne V, Mendes AA, Decaestecker K, Kiess AP, Lumen N, Phillips R, De Bruycker A, Mishra M, Rana Z, Molitoris J, Lambert B, Delrue L, Wang H, Lowe K, Verbeke S, Van Dorpe J, Bultijnck R, Villeirs G, De Man K, Ameye F, Song DY, DeWeese T, Paller CJ, Feng FY, Wyatt A, Pienta KJ, Diehn M, Bentzen SM, Joniau S, Vanhaverbeke F, De Meerleer G, Antonarakis ES, Lotan TL, Berlin A, Siva S, Ost P, Tran PT. Long-Term Outcomes and Genetic Predictors of Response to Metastasis-Directed Therapy Versus Observation in Oligometastatic Prostate Cancer: Analysis of STOMP and ORIOLE Trials. J Clin Oncol. 2022 Oct 10;40(29):3377-3382. doi: 10.1200/JCO.22.00644. Epub 2022 Aug 24.

Helpful Links

• Gleason Score Description

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 28, 2016
• Primary Completion (ACTUAL): August 30, 2018
• Study Completion (ACTUAL): October 31, 2022

Study Registration Dates

• First Submitted: February 8, 2016
• First Submitted That Met QC Criteria: February 8, 2016
• First Posted (ESTIMATE): February 11, 2016

Study Record Updates

• Last Update Posted (ACTUAL): November 29, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Prostate Cancer; Stereotactic Body Radiation Therapy; Oligometastasis; Stereotactic Ablative Radiotherapy
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: J15180; IRB00079078 (OTHER: JHMIRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO