A Phase II Double-Blinded, Placebo-Controlled Trial of Prostate Oligometastatic Radiotherapy With or Without Androgen Deprivation Therapy in Oligometastatic Prostate Cancer (NRG Promethean)
Objective
This phase II trial tests whether relugolix and radiation therapy works to shrink tumors in patients with prostate cancer that has spread in a limited way to 1 to 5 other parts of the body (oligometastatic).
Study Arms
- Placebo Comparator: Arm I (placebo, SABR)
- Experimental: Arm II (relugolix, SABR)
Eligibility
- 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 120 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
- Must meet study entry criteria based on the following diagnostic workup within 120 days prior to registration:
- History and physical examination;
- Technetium TC-99m (99mTc) bone scan (Must be negative);
- Either computed tomography (CT) or magnetic resonance imaging (MRI) of pelvis +/- abdomen (Must be negative);
- Fluciclovine or prostate-specific membrane antigen (PSMA) PET scan (Must be positive with exception of local disease);
- Note: All 3 scans are mandatory (bone scan; CT/magnetic resonance [MR]; PET)
- 1 - 5 oligometastatic lesions in bone and/or nodal/soft tissue sites on fluciclovine or PSMA PET within 120 days prior to registration and includes at least ONE of the following:
- Bone - each metastasis is counted (for example, 2 distinct lesions in the right ilium count as 2 oligometastatic lesions)
- Extrapelvic Nodal/ soft tissue - requires at least one extrapelvic inguinal or a nodal/soft tissue lesion superior to the iliac bifurcation (that is, American Joint Committee on Cancer [AJCC] M1a version 8)
- Note: Although a patient must have bone and/or extrapelvic disease to be eligible, when counting the number of oligometastatic lesions, each lymph node lesion, whether pelvic or extrapelvic, is counted (for example, 2 distinct lymph nodes in the right external iliac basin count as 2 oligometastatic lesions; one extrapelvic and one pelvic node count as 2 oligometastic lesions, etc)
- Serum total prostate-specific antigen (PSA) ≤10.0 ng/mL obtained within 120 days prior to registration that also meets ONE of the following PSA recurrence definitions:
- PSA ≥ post-radiation therapy (RT) nadir PSA + 2 ng/mL, if patient received-radiation therapy to intact prostate, or
- Current PSA ≥ 0.2 ng/mL, with a second confirmatory PSA ≥ 0.2 ng/mL if patient received a radical prostatectomy with or without post-op RT
- Must have ≥3 PSA values within the last two years since end of primary treatment or within the last 2 years prior to registration, whichever is less
- Note: PSA doubling time must be calculated by entering all PSA values since end of primary treatment or within the last 2 years prior to registration (whichever is less) into the PSA Doubling Time Calculator found at MDCalc.com
- Serum total testosterone ≥ 100 ng/dL within 120 days prior to registration
- Note: Prior androgen deprivation therapy (other than bilateral orchiectomy) is allowed if discontinued prior to registration and serum total testosterone is ≥ 100 ng/dL
- Total bilirubin: ≤ 1.5 x institutional upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, subject is eligible if direct bilirubin is ≤ 1.5 x ULN) (within 120 days prior to registration)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]): ≤ 2.5 x institutional ULN (within 120 days prior to registration)
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- The patient must agree to use a highly effective contraception (even men with vasectomies) if he is having sex with a woman of childbearing potential or with a woman who is pregnant while on study drug and for 2 weeks following the last dose of study drug
- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information.
NCT ID
NCT05053152
