Testing the Addition of the Drug Relugolix to the Usual Radiation Therapy for Advanced-Stage Prostate Cancer (NRG PROMETHEAN)

This is an interventional treatment trial for Oligometastatic Prostate Carcinoma Read More

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 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.

Exclusion Criteria:

• Clinical, biopsy-proven, or radiologic (conventional or PET imaging) evidence of local tumor recurrence in the prostate and/or periprostatic/seminal vesicle region after radiotherapy, or in the prostate bed after prostatectomy

  • Note: if a patient had a prior local recurrence and received local salvage therapy, the patient is eligible if there is no current evidence of disease in the prostate/prostate bed. Patients with positive findings on examination or imaging remain eligible if biopsy of the site is negative for cancer.
• Currently on androgen deprivation or anti-androgen therapy

• Definitive radiologic evidence of metastatic disease on conventional imaging, defined by one of the following:

  • Osseous metastasis on 99mTc radionuclide bone scan, or
  • Extra pelvic nodal/soft tissue disease (> 1.5 cm in short axis) on CT or MRI pelvis +/- abdomen

• Spinal cord compression, or spinal intramedullary, brain, and/or visceral (for example liver, lung, 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.
• 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 radiotherapy to a lesion (i.e. oligometastatic recurrence by PET)

  • Note: Lesions outside of a previously irradiated planning treatment volume (PTV) are eligible as long as the prescription isovolume dose of any prior radiotherapy course is > 2.0 cm distant from new lesion
• Inability to treat all oligometastatic sites with radiotherapy in the judgement of the investigator
• Intrapelvic lymph nodes as only site of prostate cancer recurrence
• Inability to swallow whole, undivided, unchewed, and uncrushed pills
• Known gastrointestinal disorder affecting oral medication absorption

• Co-morbidity defined as follows:

  • Patients with any comorbidities that would prohibit completion of protocol specified therapy
  • Inflammatory bowel disease in patients in whom abdominopelvic radiotherapy is planned
  • History of congenital long QT syndrome
  • Current severe or unstable angina
  • New York Heart Association functional classification III/IV heart failure (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)