Randomized Phase III Trial Incorporating Abiraterone Acetate with Prednisone and 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

Cancer Categories

Genitourinary (GU)

Karmanos Trial ID

NRG-GU008

NCT ID

NCT04134260

Age Group

Adult

Scope

National

Phase

Phase III

Principal Investigator

Brian
Yeh, M.D., Ph.D.
Oncology - Radiation View Profile

Objective:

Primary Objective

Compare metastasis-free survival (MFS) of salvage RT and GnRH agonist/antagonist vs. RT/ GnRH agonist/antagonist with abiraterone acetate with prednisone and apalutamide for patients with pathologic node-positive prostate cancer after radical prostatectomy with detectable PSA.

Secondary Objectives

Compare health-related quality of life (EPIC26, EQ5D5L, Brief Pain Inventory, PROMISFatigue) among the treatment arms.
Compare overall survival, biochemical progression-free survival, time to local-regional progression, time to castrate resistance, and cancer-specific survival among the treatment arms.
Compare the shor-tterm and long-term treatment-related adverse events among the treatment arms.

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Eligibility

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 positron emission tomography (PET) scan (FACBC, Axumin) within 90 days prior to registration that is negative for distant metastatic (M1a, M1b, M1c) disease; Note that though every effort should be made to obtain a fluciclovine F-18 PET (FACBC, Axumin) scan; however, if the patient has already had a recent F-18 PSMA PET (PyLarify) scan or gallium Ga 68-labeled PSMA-11 (Ga-68 PSMA) PET scan or C-11 or F-18 choline PET scan within 90 days prior to registration (to include scan report) then repeat molecular imaging with a fluciclovine F-18 PET (FACBC, Axumin) scan will not be required.
Pathologically node positive disease with nodal involvement only in the pelvis in the prostatectomy specimen (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
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 and within 180 days of registration and before start of GnRH agonist/antagonist
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, F-18 PSMA, PSMA, F-18 choline 11)
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

Locations

Karmanos Cancer Institute at McLaren Flint

4100 Beecher Rd
Flint, MI 48532
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Phone: 810-342-3800

Karmanos Cancer Institute at McLaren Greater Lansing - Medical Oncology and Hematology

3520 Forest Rd.
Lansing, MI 48910
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Phone: 517-975-9500

Karmanos Cancer Institute at McLaren Macomb

1080 Harrington Blvd
Mount Clemens, MI 48043
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Phone: 586-493-7510

KCI at McLaren Flint - Owosso

4100 Beecher Road
Flint, MI 48532
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Phone: (810) 342-3800

Applicable Disease Site

Therapies, Drugs, Devices