A Phase II Double-Blinded, Placebo-Controlled Trial of PROstate OligoMETastatic RadiotHErapy With or Without ANdrogen Deprivation Therapy in Oligometastatic Prostate Cancer (NRG Promethean)
Overview
- Phase
- Phase 2
- Intervention
- Biospecimen Collection
- Conditions
- Not specified
- Sponsor
- NRG Oncology
- Enrollment
- 194
- Locations
- 463
- Primary Endpoint
- Radiological progression-free survival (rPFS)
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
This phase II trial compares the usual treatment of radiation therapy alone to using the study drug, relugolix, plus the usual radiation therapy in patients with castration-sensitive prostate cancer that has spread to limited other parts of the body (oligometastatic). Relugolix is in a class of medications called gonadotropin-releasing hormone (GnRH) receptor antagonists. It works by decreasing the amount of testosterone (a male hormone) produced by the body. It may stop the growth of cancer cells that need testosterone to grow. Radiation therapy uses high-energy x rays or protons to kill tumor cells. The addition of relugolix to the radiation may reduce the chance of oligometastatic prostate cancer spreading further.
Detailed Description
PRIMARY OBJECTIVE: I. Compare conventional radiological progression-free survival (rPFS) for positron emission tomography (PET)-detected, biochemically recurrent, oligometastatic, castration-sensitive prostate cancer patients treated with stereotactic ablative body radiation therapy (SABR) plus placebo versus (vs.) SABR plus relugolix. SECONDARY OBJECTIVES: I. Compare conventional or PET-based radiological progression-free survival (prPFS) between treatment arms. II. Compare patient-reported sexual and hormonal quality of life as assessed by corresponding Expanded Prostate Cancer Index Composite Short Form (EPIC-26) domains between treatment arms. III. Compare other measures of quality of life obtained from the European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ5D-5L), European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-30), Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue instruments between the two treatment arms. IV. Compare time to salvage therapy and time to castration-resistance between treatment arms. V. Compare local progression (SABR-targeted lesion), biochemical progression, distant metastases, prostate cancer-specific mortality, metastasis-free survival, and overall survival between treatment arms. VI. Determine adverse events rates and compare rates between the two treatment arms. EXPLORATORY OBJECTIVE: I. Evaluate genomic and peripheral tissue and blood markers of treatment response. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive placebo orally (PO) once daily (QD) on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, computed tomography (CT), magnetic resonance imaging (MRI), prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial. After completion of study treatment, patients are followed up at 9 and 12 months, subsequently every 6 months to month 60, and then annually thereafter or at the time of progression.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Pathologically (histologically or cytologically) proven diagnosis of prostate adenocarcinoma at any anatomical location (for example, prostate, metastatic site), including intraductal or ductal carcinoma, at any time before registration
- •Age \>= 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2 within 180 days prior to registration
- •Prior curative-intent treatment to the prostate, by either:
- •External beam and/or brachytherapy to: Prostate alone, prostate and seminal vesicles, prostate and pelvic nodes, or radiation to all three sites
- •Radical prostatectomy alone, radical prostatectomy plus postoperative radiotherapy to the prostate bed, or radical prostatectomy plus postoperative radiotherapy to the pelvic nodes.
- •Note: Patients who have received curative intent with radiation prior to prostatectomy are eligible and should be categorized as RT to Intact Prostate since that was the first curative intent
- •Must meet study entry criteria based on the following diagnostic workup within 120 days prior to registration:
- •History and physical examination;
- •Fluciclovine or PSMA PET scan;
Exclusion Criteria
- •Currently on androgen deprivation or anti-androgen therapy
- •Spinal cord compression, or spinal intramedullary, brain, and/or visceral (for example liver, etc.) metastasis
- •Note: Spinal metastases (PET-detected) with epidural extension are eligible if there is \> 0.3 cm spatial separation between the gross tumor volume and spinal cord. Lung metastases are eligible
- •Biopsy-proven prostatic carcinoma with signet-ring, sarcomatoid, or neuroendocrine features (for example, small cell)
- •Prior metastatic or non-metastatic, invasive malignancy (except non metastatic, non-melanomatous skin cancer) unless continuously disease free for \>= 3 years
- •Prior chemotherapy for prostate cancer or bilateral orchiectomy
- •Note: Prior chemotherapy for a different cancer is allowed if continuously disease-free for \>= 3 years
- •Prior high dose radiotherapy to a lesion (i.e. oligometastatic recurrence by PET)
- •Note: Lesions included in or near a previously irradiated planning target volume (PTV) are eligible as long as previous delivered dose is estimated to be less than an EQD2 of 50 Gy
- •Inability to treat all oligometastatic sites with radiotherapy in the judgement of the investigator
Arms & Interventions
Arm I (placebo, SABR)
Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Biospecimen Collection
Arm I (placebo, SABR)
Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Bone Scan
Arm I (placebo, SABR)
Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Computed Tomography
Arm I (placebo, SABR)
Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Fluciclovine F18
Arm I (placebo, SABR)
Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Magnetic Resonance Imaging
Arm I (placebo, SABR)
Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Placebo Administration
Arm I (placebo, SABR)
Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Positron Emission Tomography
Arm I (placebo, SABR)
Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: PSMA PET Scan
Arm I (placebo, SABR)
Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Stereotactic Body Radiation Therapy
Arm II (relugolix, SABR)
Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Biospecimen Collection
Arm II (relugolix, SABR)
Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Bone Scan
Arm II (relugolix, SABR)
Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Computed Tomography
Arm II (relugolix, SABR)
Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Fluciclovine F18
Arm II (relugolix, SABR)
Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Magnetic Resonance Imaging
Arm II (relugolix, SABR)
Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Positron Emission Tomography
Arm II (relugolix, SABR)
Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: PSMA PET Scan
Arm II (relugolix, SABR)
Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Relugolix
Arm II (relugolix, SABR)
Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Intervention: Stereotactic Body Radiation Therapy
Outcomes
Primary Outcomes
Radiological progression-free survival (rPFS)
Time Frame: Time from randomization to the occurrence of radiological progression detected by conventional imaging or death from any cause, assessed up to 5 years
The rPFS curves will be estimated by the Kaplan-Meier method and compared between the two treatment arms using a one-sided, logrank test stratified by the three randomization factors.
Secondary Outcomes
- Positron emission tomography (PET)-based radiological progression-free survival(Time from randomization to the occurrence of conventional or PET-based radiological progression or death from any cause, assessed up to 5 years)
- Metastasis-free survival(From randomization to distant metastases or death from any cause, assessed up to 5 years)
- Overall survival(From randomization to death from any cause, assessed up to 5 years)
- Sexual and hormonal quality of life(Up to 5 years from randomization)
- Quality of life(Up to 5 years from randomization)
- Fatigue(Up to 5 years from randomization)
- Time from randomization to administration of salvage therapy(Up to 5 years from randomization)
- Time from randomization to castrate-resistant prostate cancer(Up to 5 years from randomization)
- Time from randomization to local progression within a stereotactic ablative body radiation therapy (SABR)-targeted lesion(Up to 5 years from randomization)
- Time from randomization to biochemical progression(Up to 5 years from randomization)
- Time from randomization to the occurrence of distance metastases(Up to 5 years from randomization)
- Time from randomization to death from prostate cancer(Up to 5 years from randomization)