Treating Prostate Cancer That Has Come Back After Surgery With Apalutamide and Targeted Radiation Using PET/CT Imaging

  • STATUS
    Recruiting
  • End date
    Dec 31, 2027
  • participants needed
    804
  • sponsor
    ECOG-ACRIN Cancer Research Group
Updated on 27 May 2022
ct scan
prostatectomy
cancer
androgens
definitive treatment
metastasis
neutrophil count
tumor cells
antiandrogen therapy
androgen suppression
bone scan
prostate specific antigen
leuprolide
goserelin
stereotactic body radiation therapy
external beam radiation therapy
apalutamide
positron emission tomography

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.

Description

PRIMARY OBJECTIVES:

I. 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:

I. 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.

V. 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.

Details
Condition Biochemically Recurrent Prostate Carcinoma, Prostate Adenocarcinoma
Treatment goserelin acetate, computed tomography, positron emission tomography, Leuprolide Acetate, 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, stereotactic body radiation therapy, external beam radiation therapy, Apalutamide, Volume Modulated Arc Therapy, Fluciclovine F18, Intensity-Modulated Proton Therapy
Clinical Study IdentifierNCT04423211
SponsorECOG-ACRIN Cancer Research Group
Last Modified on27 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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
conventional imaging modalities (CIM) (i.e., bone scans, pelvic CT, or pelvic
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)
MRI), which must be done within 10-12 weeks prior to registration. Extra-
Patient must have the ability to provide written informed consent
pelvic metastases is defined as any osseous metastases and/or any extrapelvic
Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
soft tissue, lymph nodes and organ metastases; extra-pelvic is defined as
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
superior to common iliac bifurcation, outside of standard prostate bed + whole
pelvis nodal RT fields
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)

Exclusion Criteria

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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note