Apalutamide and Gonadotropin-Releasing Hormone Analog With or Without Abiraterone Acetate in Treating Participants With Prostate Cancer
A Pre-Operative Study to Assess the Effects of Apalutamide Plus LHRH Agonist or Apalutamide Plus Abiraterone Acetate Plus LHRH Agonist for Six Months for Prostate Cancer Patients at High Risk for Recurrence
2 other identifiers
interventional
86
1 country
1
Brief Summary
This phase II trial studies how well apalutamide and gonadotropin-releasing hormone analog with or without abiraterone acetate work in treating participants with prostate cancer prior to surgery. Apalutamide and abiraterone acetate may stop the growth of cancer cells either by killing the cells or by blocking some of the enzymes needed for cell growth. Hormone therapy, using gonadotropin-releasing hormone analog, may fight prostate cancer by lowering the amount of testosterone the body makes. Giving apalutamide, gonadotropin-releasing hormone analog, and abiraterone acetate may work better in treating participants with prostate cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Oct 2017
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 7, 2017
CompletedFirst Posted
Study publicly available on registry
September 12, 2017
CompletedStudy Start
First participant enrolled
October 13, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 11, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
May 11, 2021
CompletedResults Posted
Study results publicly available
August 10, 2022
CompletedAugust 10, 2022
July 1, 2022
3.6 years
September 7, 2017
May 11, 2022
July 14, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
The Number of Participants With Rate of Pathologic Stage =< pT2N0 at Prostatectomy
The study will provide a point estimate and 95% confidence interval of the proportion of patients with pathologic stage =\< pT2N0 at prostatectomy for each arm. Patient characteristics will be summarized using descriptive statistics for each arm.
At the time of radical prostatectomy
Secondary Outcomes (4)
Number of Participants With Incidence of Adverse Events
From screening up to 4 weeks post-surgery, an average of 7 months
Tumor Epithelium Volume in the Surgical Specimen
At the time of radical prostatectomy
Assessment of Positive Surgical Margins in the Surgical Specimen
At the time of radical prostatectomy
Time to Prostate Specific Antigen Recurrence (TTRPSA)
From the date of randomization up to 4 weeks post-surgery
Other Outcomes (5)
Assessment of Steroid Hormone Metabolome in Blood Plasma and Tissue
At radical prostatectomy
Assessment of Protein and Ribonucleic Acid (RNA) Analysis Results
At radical prostatectomy
Citrate Intracellular Tricarboxylic Acid (TCA) Cycle Metabolite Concentrations
At radical prostatectomy
- +2 more other outcomes
Study Arms (2)
Arm A (LHRHa, apalutamide)
EXPERIMENTALParticipants receive gonadotropin-releasing hormone analog (leuprolide, goserelin, or triptorelin as determined by treating physician) IM once every 3 months and apalutamide PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.
Arm B (LHRHa, apalutamide, abiraterone acetate)
EXPERIMENTALParticipants receive gonadotropin-releasing hormone analog and apalutamide as in arm A, abiraterone acetate PO QD, and prednisone PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy.
Interventions
Given PO
Given PO
Given IM
Given PO
Undergo radical prostatectomy
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate with no histological variants (such as small cell, sarcomatoid, pure ductal cancer, transitional cell carcinoma).
- Patients may have received one prior depot injection of LHRH agonist or LHRH antagonist (degarelix) within 30 days prior to study entry. Patients who have received any other prior hormonal therapy or any chemotherapy for prostate cancer will be excluded. (Patients who have discontinued finasteride or dutasteride or testosterone supplement for at least 2 weeks will be allowed to enroll).
- Be willing/able to adhere to the prohibitions and restrictions specified in this protocol.
- Have signed an informed consent document indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study.
- Written authorization for use and release of health and research study information has been obtained.
- Pathology review at Monroe Dunaway (MD) Anderson (Note: if patient's prostate biopsy was not read at MD Anderson, it must be reviewed at the study site to confirm eligibility).
- Prostate biopsy. If previous biopsy has been performed within 3 months of screening, second biopsy procedure will not be required, if archival biopsies and at least one formalin fixed paraffin embedded biopsy tissue block containing tumor is available.
- The following tumor stage and Gleason scores: a) clinical \>= stage T1c/T2 tumor with Gleason score \>=8 b) clinical stage \>= T2b tumor with Gleason score \>= 7 and PSA \> 10 ng/ml.
- Serum testosterone \> 150 ng/dL. For patients treated up to 1 month of LHRH agonist, a testosterone measurement prior to the LHRH treatment will be used to determine eligibility, and must have been \> 150 ng/dL. If no testosterone level is available from before LHRHa injection up to 30 days prior to study entry, the patient will be ineligible.
- Patient is suitable for prostatectomy.
- No evidence of metastatic disease as determined by imaging procedures.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Hemoglobin \>= 9.0 g/dL independent of transfusion.
- Platelet count \>= 100,000/uL.
- Absolute peripheral neutrophil count (ANC) \> 1,000.
- +10 more criteria
You may not qualify if:
- Patients who have had any prior chemotherapy or radiotherapy for prostate cancer.
- Patients who have had \> 1 LHRH agonist or antagonist depot injection or received depot injection \> 30 days before study entry.
- Patients may not be receiving any other investigational agents.
- Patients may not be receiving the concomitant administration of any systemic therapy, biologic therapy, or other agents with anti-tumor activity against prostate cancer while the patients are on study.
- Patients with known metastatic prostate cancer.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to leuprolide acetate, abiraterone acetate, prednisone or apalutamide or other agents used in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with apalutamide and abiraterone. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
- Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment. If a strong CYP3A4 inducer must be co-administered, increase the abiraterone acetate dosing frequency.
- Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate.
- Patients receiving medications known to lower the seizure threshold are ineligible unless discontinued or substituted at least 4 weeks prior to study entry. These include: 1) aminophylline/theophylline; 2) atypical antipsychotics (e.g., clozapine, olanzapine, risperidone, ziprasidone); 3) bupropion; 4) lithium; 5) pethidine; 6) phenothiazine antipsychotics (e.g., prochlorperazine (compazine), chlorpromazine, mesoridazine, thioridazine); 7) tricyclic and tetracyclic antidepressants (e.g., amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine).
- Chronically uncontrolled hypertension, defined conventionally as consistent systolic pressures above 170 or diastolic pressures above 110 despite anti-hypertensive therapy. Note that this is NOT a criterion related to particular blood pressure (BP) results at the time of assessment for eligibility, nor does it apply to acute BP excursions that are related to iatrogenic causes, acute pain or other transient, reversible causes. (for example doctor's visit related stress i.e. "white coat syndrome".
- Requirement for corticosteroids greater than the equivalent of 10 mg of prednisone daily for more than 2 weeks.
- Poorly controlled diabetes defined by hemoglobin A1C \> 9.0 at screening.
- Active or symptomatic viral hepatitis or chronic liver disease.
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Venkatesh N, Chauhan PK, Mukhida SS, Grewal K, Aparicio A, Pilie PG, Subudhi SK, Corn PG, Sachdeva A, Desai M, Siddiqui BA, Zurita AJ, Pain D, Gregg JR, Frigo DE, Logothetis CJ, Msaouel P, Koutroumpakis E, Hahn AW. Evaluating Clinical Tools to Monitor Cardiovascular Risk in Men With Prostate Cancer Receiving Hormone Therapy. JCO Oncol Pract. 2025 Nov 7:OP2500506. doi: 10.1200/OP-25-00506. Online ahead of print.
PMID: 41202201DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Christopher Logothetis, MD-Professor, Genitourinary Medical Oncology
- Organization
- UT MD Anderson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Christopher Logothetis
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 7, 2017
First Posted
September 12, 2017
Study Start
October 13, 2017
Primary Completion
May 11, 2021
Study Completion
May 11, 2021
Last Updated
August 10, 2022
Results First Posted
August 10, 2022
Record last verified: 2022-07