Phase III Study of Local or Systemic Therapy INtensification DIrected by PET in Prostate CAncer Patients with Post-ProstaTEctomy Biochemical Recurrence (INDICATE).
Primary Objectives:
1. For patients without PET-evidence of extrapelvic metastases, to evaluate whether the addition of enhanced systemic therapy to SOC salvage RT could prolong PFS.
2. 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 in each arm.
2. To evaluate event-free survival in each arm.
3. To evaluate time to PSA progression using Prostate Cancer Working Group(PCWG) 3 criteria in each arm.
4. To assess the incidence of adverse events with the addition of enhanced systemic therapy in patients without PET-evidence of extrapelvic metastases.
5. 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.
6. To estimate the detection rate of PET/CT at the patient and regional level, and to evaluate its concordance with the follow-up FDA approved conventional imaging modalities considered standard-of care (SOC) per institution, including CT, bone scintigraphy, MRI and PET imaging performed as PET/CT and/or PET/MR using 11C-Choline and/or 18F-Sodium Fluoride.
7. 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.
8. To determine the value of repeat PET at time of second PSA progression, or 12 months after completion of enhanced systemic therapy, whichever comes first (PET2) to assess response to therapy (enhanced systemic therapy +/- focal RT and/or ADT) compared to standard response assessments (PSA and CIM).
GnRH agonists
LEUPROLIDE
- Rutgers Cancer Institute of New Jersey
Inclusion Criteria
- STEP 0: REGISTRATION ELIGIBILITY 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 as follows:
- If time to BCR, defined as time to first detectable PSA ( > lower limit of normal
for assay used) 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 (Note: patients with a persistent PSA reading of at
least 0.2 ng/mL are eligible)
- If time to BCR, defined as time to first detectable PSA (> lower limit of normal
for assay used) after RP, is >= 12 months, a minimum absolute PSA of 0.5 ng/mL is
required
- If the patient has a detectable PSA (> lower limit of normal for assay used) at
any time after RP AND has an eligible baseline SOC PET (PET1) with at least one
positive lesion in any location, then there is no minimum PSA requirement
- 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
- Study eligible = PET using FDA-approved radiotracer and performed within 16 weeks
prior to study 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 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
- Hemoglobin (Hgb) >= 9.0 g/dL (independent of transfusion and/or growth factors within
3 months prior to Step 0 registration) (obtained within 8 weeks prior to Step 0
registration)
- Leukocytes >= 3,000/mcL (obtained within 8 weeks prior to Step 0 registration)
- Absolute neutrophil count >= 1,500/mcL (obtained within 8 weeks prior to Step 0
registration)
- Platelets >= 100,000/mcL (obtained within 8 weeks prior to Step 0 registration)
- Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (patients with
Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, must have a direct bilirubin of
< 1.5 x ULN to be eligible) (obtained within 8 weeks prior to Step 0 registration)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional ULN (obtained within 8 weeks prior to Step 0 registration)
- Creatine < 1.5 x instituional ULN (or measured creatinine clearance > 30 mL/min)
- Human immunodeficiency virus (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
- NOTE: Sites cannot translate the associated QOL forms
- STEP 1: RANDOMIZATION ELIGIBILITY CRITERIA
- Patient must have completed a baseline SOC PET/CT or PET/MR (PET1 scan) using FDA
approved radiotracer with results of extra-pelvic metastases involvement known
(positive or negative). The PET1 must have been completed after Step 0 registration
and prior to Step 1 randomization OR up to 12 weeks prior to Step 0 registration
- 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 (1 - 5 or > 5 extra-pelvic
lesions)
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.