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Adding apalutamide to hormone and radiation therapy after prostate cancer surgery

Randomized Phase III Trial Incorporating Apalutamide and Advanced Imaging Into Salvage Treatment for Patients With Node-Positive Prostate Cancer After Radical Prostatectomy (INNOVATE*) *INtensifying Treatment for NOde Positive Prostate Cancer by VArying the Hormonal ThErapy

Phase 3 Interventional NRG Oncology · NCT04134260

This study is testing if adding apalutamide to hormone and radiation therapy helps men with lymph node positive prostate cancer live longer without the cancer spreading after surgery.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment586 (estimated)
Ages18 Years and up
SexMale
SponsorNRG Oncology Academic / other
Drugs / interventionschemotherapy, radiation, prednisone
Locations347 sites (Phoenix, Arizona and 346 other locations)
Trial IDNCT04134260 on ClinicalTrials.gov

What this trial studies

This phase III trial investigates the effectiveness of adding apalutamide to standard hormone therapy and radiation therapy in patients with lymph node positive prostate cancer following surgery. The study aims to compare metastasis-free survival between two treatment groups: one receiving standard therapy and the other receiving therapy with apalutamide. Secondary objectives include assessing quality of life, overall survival, and treatment-related adverse events. The trial also explores the validation of genomic biomarkers to improve prognostic predictions for this patient population.

Who should consider this trial

Good fit: Ideal candidates are men with pathologically confirmed prostate adenocarcinoma who have undergone radical prostatectomy and have node-positive disease.

Not a fit: Patients with distant metastatic disease or those who do not meet the specific eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve outcomes and prolong the time without disease progression for patients with prostate cancer.

How similar studies have performed: Other studies have shown promising results with similar approaches, indicating potential for success in this trial.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Pathologically (histologically) proven diagnosis of prostate adenocarcinoma. Any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted
* Any T-stage is eligible (American Joint Committee on Cancer \[AJCC\] 8th edition \[ed\])
* Appropriate stage for study entry based on fluciclovine F-18 PET scan (FACBC, Axumin) F-18 prostate-specific membrane antigen (PSMA) PET (PyLarify) scan, Gallium-68 PSMA PET scan, flotufolastat F-18 PSMA PET scan (Posluma), or C-11 or F-18 Choline PET within 90 days prior to registration that is negative for distant metastatic (M1a, M1b, M1c) disease. For patients with PSA \< 0.20 ng/mL at time of registration, PET scan is recommended but not required
* Pathologically node positive disease with nodal involvement only in the pelvis in the prostatectomy specimen or nodal disease on imaging at time of recurrence (including external iliacs, internal iliacs, and/or obturator nodes); peri-prostatic and peri-rectal nodes can also be considered regional lymphadenopathy and are allowed
* History/physical examination within 90 days prior to registration
* Age \>= 18
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 90 days prior to registration
* Detectable PSA after radical prostatectomy. Detectable PSA is defined as serum PSA \> 0 ng/mL at least 30 days after prostatectomy
* Patients who have already started on post-prostatectomy GnRH agonist/antagonist for =\< 180 days prior to registration are eligible (Note: patients who started on an oral antiandrogen are eligible if started =\< 180 days and stopped prior to registration)
* Hemoglobin \>= 9.0 g/dL, independent of transfusion and/or growth factors (within 90 days prior to registration)
* Platelet count \>= 100,000 x 10\^9/uL independent of transfusion and/or growth factors (within 90 days prior to registration)
* Serum potassium \>= 3.5 mmol/L within 90 days prior to registration
* Creatinine clearance (CrCl) \>= 30 mL/min estimated by Cockcroft-Gault (please use actual weight for calculation unless greater than 30% above ideal body weight then use the adjusted body weight) (within 90 days prior to registration)
* 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, measure direct and indirect bilirubin and if direct bilirubin is =\< 1.5 x ULN, subject is eligible) (within 90 days prior to registration)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (within 90 days prior to registration)
* Serum albumin \>= 3.0 g/dL (within 90 days prior to registration)
* Discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to registration
* The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial and have a CD4 count \>= 200 cells/microliter within 30 days prior to registration. Note: HIV testing is not required for eligibility for this protocol
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy within 30 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol
* 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 within 30 days prior to registration
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ) who has no evidence of disease for \< 3 years must contact the principal investigator, Ronald Chen, Doctor of Medicine (MD)
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Exclusion Criteria:

* Definitive radiologic evidence of metastatic disease (M1a, M1b or M1c) on molecular imaging (e.g. Fluciclovine F-18 PET, \[FACBC, Axumin\], F-18 PSMA PET \[Pylarify\], flotufolastat F-18 PSMA PET scan \[Posluma\], Gallium-68 PSMA PET scan or C-11 choline PET)
* Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowed (completed \> 3 years prior to registration)
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* Androgen deprivation therapy (ADT) prior to radical prostatectomy
* Prior treatment with androgen receptor signaling inhibitor (including but not exclusive to a growing list of: abiraterone acetate, enzalutamide, apalutamide, darolutamide), unless started =\< 180 days and stopped prior to registration, which is allowed
* Current use of 5-alpha reductase inhibitor. NOTE: if the alpha reductase inhibitor is stopped prior to randomization the patient is eligible
* History of any of the following:

  * Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year prior to registration, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system \[CNS\] or meningeal disease which may require treatment with surgery or radiation therapy)
  * Severe or unstable angina, myocardial infarction, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 12 months prior to registration
  * New York Heart Association functional classification III/IV (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.)
  * History of any condition that in the opinion of the investigator, would preclude participation in this study
* Current evidence of any of the following:

  * Known gastrointestinal disorder affecting absorption of oral medications
  * Active uncontrolled infection
  * Presence of uncontrolled hypertension (persistent systolic blood pressure \[BP\] \>= 160 mmHg or diastolic BP \>= 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment
  * Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily
  * Baseline moderate and severe hepatic impairment (Child-Pugh Class B \& C)
  * Inability to swallow oral pills
  * Any current condition that in the opinion of the investigator, would preclude participation in this study
* Patients must not plan to participate in any other therapeutic clinical trials while receiving treatment on this study
* Patients with inflammatory bowel disease

Where this trial is running

Phoenix, Arizona and 346 other locations

+297 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Prostate AdenocarcinomaStage I Prostate Cancer AJCC v8Stage II Prostate Cancer AJCC v8Stage III Prostate Cancer AJCC v8Stage IVA Prostate Cancer AJCC v8
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.