Clinical Trial 23303

• Overview

  Study Title:

  Phase III Study of Local or Systemic Therapy INtensification DIrected by PET in Prostate CAncer Patients with Post-ProstaTEctomy Biochemical Recurrence (INDICATE)

  Summary:

  This phase III trial tests two questions by two separate comparisons of therapies. The first question is whether enhanced therapy (apalutamide in combination with abiraterone + prednisone) added to standard of care (prostate radiation therapy and short term androgen deprivation) is more effective compared to standard of care alone in patients with prostate cancer who experience biochemical recurrence (a rise in the blood level of prostate specific antigen [PSA] after surgical removal of the prostate cancer). A second question tests treatment in patients with biochemical recurrence who show prostate cancer spreading outside the pelvis (metastasis) by positron emission tomography (PET) imaging. In these patients, the benefit of adding metastasis-directed radiation to enhanced therapy (apalutamide in combination with abiraterone + prednisone) is tested.

  Objective:

  Primary Objectives * For patients without PET-evidence of extrapelvic metastases, to evaluate whether the addition of enhanced systemic therapy to SOC salvage RT could prolong PFS. * For patients with PET-evidence of extrapelvic metastases, to evaluate whether the addition of metastasis-directed RT to enhanced systemic therapy and SOC salvage RT could prolong PFS. Secondary Objectives * To evaluate overall survival in each arm. * To evaluate event-free survival in each arm. * To evaluate time to PSA progression in each arm. * To assess the incidence of adverse events with the addition of enhanced systemic therapy in patients without PET-evidence of extrapelvic metastases. * To assess the incidence of adverse events with local ablative metastasis-directed RT for PET-positive metastatic disease in patients with PET-evidence of extrapelvic metastases. * To estimate the detection rate of PET at the patient and regional level, and to evaluate its concordance with the follow-up FDA-approved CIM (as available) considered standard-of-care (SOC) per institution. including CT, bone scintigraphy, MRI and PET imaging. * To determine the distribution of PET-positive lesions among anatomic sites (prostate fossa, intrapelvic soft tissue/lymph node, extrapelvic soft tissue/lymph node, and bone metastases) in patients with post-RP BCR, correlated with PSA (level, doubling time, velocity) and other relevant clinical parameters.

• Treatments

  Therapies:

  Hormonal Therapy; Radiotherapy

  Medications:

  Apalutamide (); Decapeptyl SR (Triptorelin); Degarelix (); Lupron (leuprolide acetate); Relugolix (Orgovyx); Triptorelin (); goserelin acetate (Zoladex); leuprolide acetate ()

• Inclusion Criteria

  • Patient must be male and >= 18 years of age.
  • Patient must have had a radical prostatectomy (RP) as definitive therapy for histopathologically-proven prostatic adenocarcinoma
  • Patient must have biochemical recurrence (BCR) after RP, defined per protocol
  • Patients must have no definite evidence for extrapelvic metastatic disease by conventional imaging modalities (CIM) (CT abdomen/pelvis or MRI abdomen/pelvis AND bone scintigraphy, or equivalent), within 26 weeks prior to Step 0 registration. If a patient only has a study-eligible PET/CT or PET/MR (i.e., PET done without prior CIM): if the PET is negative for extrapelvic lesions, then baseline CIM is NOT required. If the PET positive for extrapelvic lesions, then patient should have a baseline CT/MRI for soft tissue lesions and/or a bone scan for osseous lesions
  • Extra-pelvic metastases is defined as any osseous metastases and/or any extrapelvic soft tissue, lymph nodes and organ metastases; extra-pelvic is defined as superior to common iliac bifurcation, outside of standard prostate bed + whole pelvis nodal RT fields. Baseline PET/CT or PET/MR scan (PET1) is eligible for this study if the SOC PET scan is completed with an FDA approved radiotracer for prostate cancer after Step 0 registration and prior to Step 1 randomization OR up to 16 weeks prior to Step 0 registration
  • Patient must be a candidate for SOC post-prostatectomy radiation therapy (RT) to the prostate bed and pelvic nodes with androgen deprivation therapy (ADT)
  • Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Patient must not have started ADT for biochemical recurrence prior to baseline PET (PET1) imaging. A short course of low-dose anti-androgen such as bicalutamide, given after baseline study PET/CT but prior to study registration, is permitted as a brief temporizing measure in advance of starting protocol-approved SOC ADT.
  • Patient must not be enrolled in another therapeutic clinical trial
  • Patient must be able to lie flat and still for approximately 20-30 minutes or otherwise tolerate a PET scan and radiation treatment planning and delivery
  • Patients undergoing a PET/MR must meet local institutional safety guidelines for MRI
  • Patient must not have history of seizures or known condition that may cause predisposal to seizures (e.g., stroke or head trauma resulting in loss of consciousness) within 1 year prior to registration
  • Patient must not have history of inflammatory bowel disease or any gastrointestinal disorder affecting absorption that is expected to increase risk of complication from radiotherapy
  • HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • 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. To be eligible for this trial, patients should be class I or II (by patient symptoms) or A or B (by objective assessment)
  • Patient must not have completed a course of prior pelvic radiation therapy for any reason
  • Patient must agree not to father children while on study
  • Patient must be English or Spanish speaking to be eligible for the QOL component of the study
  • Additional Inclusion criteria will apply

• Exclusion Criteria

  • Does not meet inclusion criteria

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