Summary

Eligibility
for males ages 18 years and up (full criteria)
Location
at UCSD
Dates
study started
estimated completion
Principal Investigator
by James M. Randall (ucsd)
Headshot of James M. Randall
James M. Randall

Description

Summary

This phase III trial compares the addition of apalutamide, with or without targeted radiation therapy, to standard of care treatment versus standard of care treatment alone in patients with prostate cancer biochemical recurrence (a rise in the blood level of prostate-specific antigen [PSA] after treatment with surgery or radiation). Diagnostic procedures, such as positron emission tomography/computed tomography (PET/CT), may help doctors look for cancer that has spread to the pelvis. Androgens can cause the growth of prostate cancer cells. Apalutamide may help fight prostate cancer by blocking the use of androgens by the tumor cells. Targeted radiation therapy uses high energy rays to kill tumor cells and shrink tumors that have spread. This trial may help doctors determine if using PET/CT results to deliver more tailored treatment (i.e., adding apalutamide, with or without targeted radiation therapy, to standard of care treatment) works better than standard of care treatment alone in patients with biochemical recurrence of prostate cancer.

Official Title

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

Details

PRIMARY OBJECTIVES:

  1. For patients without PET-evidence of extrapelvic metastases, to evaluate whether the addition of enhanced systemic therapy to standard of care (SOC) salvage radiation therapy (RT) could prolong progression-free survival (PFS).

II. 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:

  1. To evaluate overall survival (OS) in each arm. II. To evaluate event-free survival (EFS) in each arm. III. To evaluate time to prostate-specific antigen (PSA) progression using Prostate Cancer Working Group (PCWG) 2 criteria in each arm.

IV. To assess the incidence of adverse events with the addition of enhanced systemic therapy in patients without PET-evidence of extrapelvic metastases.

  1. 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.

VI. To estimate the detection rate of PET/CT at the patient and regional level, and to evaluate its concordance with the follow-up Food and Drug Administration (FDA)-approved conventional imaging modalities (CIM) considered standard-of-care per institution, including CT, bone scintigraphy, magnetic resonance imaging (MRI) and PET imaging performed as PET/CT and/or PET/MR using 11C-choline and/or 18F-sodium fluoride.

VII. 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-radical prostatectomy (RP) biochemical recurrence (BCR), correlated with PSA (level, doubling time, velocity) and other relevant clinical parameters.

VIII. To determine the value of repeat PET at 12 months (PET2) to assess response to therapy (enhanced systemic therapy +/- focal RT and/or androgen deprivation therapy [ADT]) compared to standard response assessments (PSA and CIM).

OUTLINE:

STEP 0: Patients receive fluciclovine F18 intravenously (IV) and undergo SOC PET/CT scan at baseline. NOTE: Patients randomized to Arms C or D below undergo a repeat fluciclovine F18 PET/CT at time of second PSA recurrence or 12 months after completion of enhanced systemic therapy.

STEP 1: Patients are randomized to 1 of 4 arms based on results of fluciclovine F18 PET/CT in Step 0.

ARM A (PET NEGATIVE FOR EXTRA PELVIC-METASTASES): Patients undergo SOC external beam radiation therapy (EBRT) for 6 months. Patients also receive goserelin acetate subcutaneously (SC) or leuprolide acetate intramuscularly (IM) for 6 months starting up to 3 months prior to EBRT but no later than the first fraction of EBRT. All treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.

ARM B (PET NEGATIVE FOR EXTRA PELVIC-METASTASES): Patients undergo SOC EBRT and receive goserelin acetate SC or leuprolide acetate IM as in Arm A. Patients also receive apalutamide orally (PO) once daily (QD) for 6 months in the absence of disease progression or unacceptable toxicity.

ARM C: (PET POSITIVE FOR EXTRA PELVIC-METASTASES): Patients undergo SOC EBRT and receive goserelin acetate SC or leuprolide acetate IM as in Arm A. Patients also receive apalutamide PO QD as in Arm B.

ARM D (PET POSITIVE FOR EXTRA PELVIC-METASTASES): Patients undergo SOC EBRT and receive goserelin acetate SC or leuprolide acetate IM as in Arm A and apalutamide PO QD as in Arm B. Patients also undergo stereotactic body radiation therapy (SBRT) or 3-dimensional (3D) conformal radiation therapy (CRT), intensity-modulated radiation therapy (IMRT) (including volume modulated arc therapy [VMAT]), and intensity-modulated proton therapy (IMPT) over 3-5 fractions in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for years 1-3 and then every 6 months for years 4-5.

Keywords

Biochemically Recurrent Prostate Carcinoma, Prostate Adenocarcinoma, Prostatic Neoplasms, Adenocarcinoma, Leuprolide, Goserelin, 3-Dimensional Conformal Radiation Therapy, Apalutamide, Computed Tomography, External Beam Radiation Therapy, Fluciclovine F18, Goserelin Acetate, Intensity-Modulated Proton Therapy, Intensity-Modulated Radiation Therapy, Leuprolide Acetate, Positron Emission Tomography, Stereotactic Body Radiation Therapy, Volume Modulated Arc Therapy, EBRT, goserelin, leuprolide, EBRT, goserelin, leuprolide, apalutamide, EBRT, goserelin, leuprolide, apalutamide, RT

Eligibility

You can join if…

Open to males ages 18 years and up

  • STEP 0: REGISTRATION ELIGIBILITY CRITERIA
  • Patient must have had a radical prostatectomy (RP) as definitive therapy for histopathologically-proven prostatic adenocarcinoma
  • Patient must have biochemical recurrence (BCR) after RP, with rising PSA defined as follows:
    • If time to biochemical recurrence, (defined as time to first detectable PSA after RP) is < 12 months, a minimum PSA level of >= 0.2 ng/mL and a confirmatory reading of >= 0.2 ng/mL is required, per the American Urological Association (AUA) definition (this includes patients with a persistent PSA reading of at least 0.2 ng/mL)
    • If time to biochemical recurrence, (defined as time to first detectable PSA after RP) is >= 12 months, a minimum absolute PSA of 0.5 ng/mL is required
      • NOTE: Qualifying PSA values per above must be collected at least 4 weeks after RP, with confirmatory persistent or elevated PSA collected at any subsequent time point
  • Patient must be negative or equivocal for extrapelvic metastatic disease by conventional imaging modalities (CIM) (i.e., bone scans, pelvic CT, or pelvic MRI), which must be done within 10-12 weeks prior to registration. 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 scan (PET1) are eligible for this study if the SOC PET scan using 18F-fluciclovine (Axumin) is completed during step 0 registration or up to 12 weeks prior to step 0 registration. The PET/CT scanners must meet scanner qualifications and scans must have an interpretation (or confirmation of an institutional clinical read) by a nuclear medicine physician or radiologist who has undergone 18F-fluciclovine (Axumin) reader training
  • Patient must be a candidate for standard-of-care (SOC) post-prostatectomy radiation therapy (RT) to the prostate bed and pelvic nodes with androgen deprivation therapy (adjuvant)
  • Patient must have the ability to provide written informed consent
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Patient must be able to lie flat and still for approximately 20-30 minutes or otherwise tolerate a PET/CT scan and radiation treatment planning and delivery
  • Patient must be at a participating institution, which has agreed to perform the imaging research studies, completed the ECOG-American College of Radiology Imaging Network (ACRIN) defined PET/CT scanner qualification procedures and received ECOG-ACRIN PET/CT scanner approval
  • Leukocytes >= 3,000/mcL (obtained within 4 weeks prior to registration)
  • Absolute neutrophil count >= 1,500/mcL (obtained within 4 weeks prior to registration)
  • Platelets >= 100,000/mcL (obtained within 4 weeks prior to registration)
  • Total bilirubin =< institutional upper limit of normal (ULN) (obtained within 4 weeks prior to registration)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 4 weeks prior to registration)
  • Glomerular filtration rate (GFR) > 35 mL/min estimated by Cockcroft-Gault or measured directly by 24 hour urine creatinine (obtained within 4 weeks prior to registration)
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • 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
  • 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)
  • STEP 1: RANDOMIZATION ELIGIBILITY CRITERIA
  • Patient must have completed a baseline SOC PET scan (PET1) with results of extra-pelvic metastases involvement known (positive or negative)
  • For patients with negative extra-pelvic metastases, PET-imaging status of intra-pelvic nodes must be known (positive or negative)
  • For patients with positive extra-pelvic metastases (defined as any PET positive lesions outside of standard salvage RT fields [prostate bed +/- typical whole pelvis]), the number of extra-pelvic lesions must be known (=< 5 or > 5 pelvic lesions)

You CAN'T join if...

  • Patient must not have started androgen deprivation therapy for biochemical recurrence prior to baseline study PET/CT imaging
  • Patient must not be enrolled in another therapeutic clinical trial
  • Patient must not have any other malignancy within the last 2 years, other than superficial bladder cancer and skin basal cell carcinoma or cutaneous superficial squamous cell carcinoma that has not metastasized
  • 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 of registration
  • Patient must not have history of inflammatory bowel disease as this would increase risk of complication from radiotherapy or any gastrointestinal disorder affecting absorption
  • Patient must not have had prior radiation therapy

Locations

  • UC San Diego Moores Cancer Center accepting new patients
    La Jolla California 92093 United States
  • Los Angeles County-USC Medical Center in progress, not accepting new patients
    Los Angeles California 90033 United States
  • USC / Norris Comprehensive Cancer Center in progress, not accepting new patients
    Los Angeles California 90033 United States
  • City of Hope Comprehensive Cancer Center accepting new patients
    Duarte California 91010 United States

Lead Scientist at UC Cancer

  • James M. Randall (ucsd)
    Dr. Randall has recently joined the division, and is building a clinical research program focused on urologic cancer. He is also interested in interventions that may identify and help patients with forms of cancer-related distress, including depression and suicidal ideation.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
ECOG-ACRIN Cancer Research Group
ID
NCT04423211
Phase
Phase 3 Prostate Cancer Research Study
Study Type
Interventional
Participants
Expecting 804 study participants
Last Updated