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Neoadjuvant And Adjuvant Abiraterone Acetate + Apalutamide Prostate Cancer Undergoing Prostatectomy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02903368
Recruitment Status : Active, not recruiting
First Posted : September 16, 2016
Last Update Posted : May 27, 2019
Sponsor:
Collaborator:
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute

Brief Summary:

This research study is studying a combination of drugs called abiraterone acetate and Apalutamide as a possible treatment for new diagnosed Prostate Cancer.

The following interventions will be use in this study :

  • Abiraterone Acetate
  • Prednisone
  • Apalutamide
  • Leuprolide Acetate

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Apalutamide Drug: Leuprolide Drug: Prednisone Drug: Abiraterone Acetate Procedure: Radical Prostatectomy Other: Observation-Post RP Phase 2

Detailed Description:

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has approved Abiraterone acetate with prednisone as a treatment option for prostate cancer that has spread to other parts of the body (metastatic castration-resistant prostate cancer).However, in this study it is being investigated for the treatment of localized prostate cancer prior to surgical removal of the prostate (prostatectomy).

Abiraterone acetate works by decreasing the production of androgens (male sex hormones), which promote prostate cancer growth. Some steroids produced by the adrenal glands can turn into testosterone, and prostate cancer cells feed on testosterone. Testosterone is suppressed by an FDA approved drug called leuprolide or Lupron.

The FDA has not approved Apalutamide as a treatment for any disease. In this study, Apalutamide is being investigated for the treatment of prostate cancer. Apalutamide also works by blocking the effects of male sex hormones.

In this research study, the investigators are studying the effectiveness of one combination of drugs (abiraterone acetate + prednisone + leuprolide) compared to another combination of drugs (abiraterone acetate + prednisone + leuprolide + Apalutamide) before surgery to see if this will improve surgical outcomes and reduce or eliminate Prostate Cancer.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Randomized Study Of Neoadjuvant And Adjuvant Abiraterone Acetate + Apalutamide For Intermediate-High Risk Prostate Cancer Undergoing Prostatectomy
Study Start Date : October 2016
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Apalutamide & Abiraterone Acetate

Eligible Participants will be randomized to receive;

  • Abiraterone acetate, Apalutamide, Leuprolide, Prednisone (6 months)
  • Radical Prostatectomy (RP)
Drug: Apalutamide
Apalutamide is administered orally once daily up
Other Names:
  • JNJ-56021927
  • ARN-509

Drug: Leuprolide
Leuprolide is administered via injection every 3 months.
Other Names:
  • Lupron
  • Eligard

Drug: Prednisone

Prednisone is administered orally once daily for patients on Abiraterone Acetate Only.

Prednisone is administered orally twice daily for patients on Apalutamide and Abiraterone. Acetate.

Other Name: Deltasone

Drug: Abiraterone Acetate
Orally once daily predetermined dose
Other Name: Zytiga

Procedure: Radical Prostatectomy
Surgery

Experimental: Abiraterone Acetate

Eligible Participants will be randomized to receive;

  • Abiraterone acetate, Leuprolide, Prednisone (6 months)
  • RP
Drug: Leuprolide
Leuprolide is administered via injection every 3 months.
Other Names:
  • Lupron
  • Eligard

Drug: Prednisone

Prednisone is administered orally once daily for patients on Abiraterone Acetate Only.

Prednisone is administered orally twice daily for patients on Apalutamide and Abiraterone. Acetate.

Other Name: Deltasone

Drug: Abiraterone Acetate
Orally once daily predetermined dose
Other Name: Zytiga

Procedure: Radical Prostatectomy
Surgery

Observation-Post RP

Following RP, patient will be randomized

  • Patients will be followed and observed by the physician.
  • no treatment and observation only (current standard of care)
Other: Observation-Post RP
No adjuvant therapy

Experimental: Apalutamide & Abiraterone Acetate-Post RP

Following RP, patient will be randomized

- 12 months of abiraterone acetate, Apalutamide, leuprolide and prednisone

Drug: Apalutamide
Apalutamide is administered orally once daily up
Other Names:
  • JNJ-56021927
  • ARN-509

Drug: Leuprolide
Leuprolide is administered via injection every 3 months.
Other Names:
  • Lupron
  • Eligard

Drug: Prednisone

Prednisone is administered orally once daily for patients on Abiraterone Acetate Only.

Prednisone is administered orally twice daily for patients on Apalutamide and Abiraterone. Acetate.

Other Name: Deltasone

Drug: Abiraterone Acetate
Orally once daily predetermined dose
Other Name: Zytiga




Primary Outcome Measures :
  1. Minimal Residual Disease [ Time Frame: 2 years ]
  2. Pathological Complete Response [ Time Frame: 2 Years ]

Secondary Outcome Measures :
  1. Progression Free Survival Rate [ Time Frame: 3 years ]
  2. Proportion Of Participants With pathological complete response (pCR) at radical Prostatectomy (RP) [ Time Frame: 2 years ]
  3. Proportion Of Participants With Favorable Residual Cancer Burden (RCB) [ Time Frame: 2 years ]
  4. Proportion Of Participants With Cribriform at RP, [ Time Frame: 2 years ]
  5. Proportion Of Participants With Intraductal Spread at RP, [ Time Frame: 2 years ]
  6. Proportion Of Participants With Positive Surgical Margins [ Time Frame: 2 years ]
  7. PSA Kinetics Prior To RP [ Time Frame: 2 years ]
  8. Quality of Life [ Time Frame: 2 years ]
    The QOL will be measured using the Expanded Prostate Cancer Index Composite 26 (EPIC-26). The questionnaires will be administered at baseline, prior to RP and every 3 months for 2 years post RP

  9. Quantitative MRI [ Time Frame: 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male ≥ 18 years of age.
  2. Histologically confirmed adenocarcinoma of the prostate without histological variants comprising >50% of the sample as determined by academic center central review (including neuroendocrine differentiation, small cell, sarcomatoid, ductal adenocarcinoma, squamous or transitional cell carcinoma).
  3. Must have 3 core biopsies involved with cancer (a minimum of 6 core biopsies must be obtained). Prostate biopsy must be within seven months from screening. Less than 3 core biopsies are allowed if the patient has >1 cm or T3 disease on MRI.
  4. Patients must have the following features:

    • Gleason ≥ 4+3=7 OR
    • Gleason 3+4=7 AND at least one of the following: PSA >20 ng/dL or T3 disease (as determined by MRI).
  5. No evidence of metastatic disease as determined by radionuclide bone scans and CT/MRI. Lymph nodes must be less than 20 mm in the short (transverse) axis.
  6. Participants must be candidates for RP and considered surgically resectable by urologic evaluation.
  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  8. Participants must have normal organ and marrow function as defined below:

    • Hemoglobin ≥ 9.0 g/dL
    • Absolute neutrophil count (ANC) ≥ 1,500/mcL
    • Platelets ≥ 100,000/mcL, independent of transfusions/growth factors within 3 months of treatment start
    • Serum potassium ≥ 3.5 mmol/L
    • Serum total bilirubin ≤ 2.0 x upper limit of normal (ULN) (except in subjects with Gilbert's syndrome who have a total bilirubin > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject may be eligible)
    • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN
    • Serum albumin ≥ 3.0 g/dL
    • Serum creatinine < 2.0 x ULN
    • PTT≤60
  9. Participant must agree to use a condom (even men with vasectomies) and another effective method of birth control if having sex with a woman of childbearing potential or must 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. Participant must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.
  10. Medications known to lower the seizure threshold (see list under APPENDIX D: Representative Medications that May Predispose to Seizure) must be discontinued or substituted at least 1 week prior to study treatment.

Exclusion Criteria:

  1. Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens (including first-generation antiandrogens, enzalutamide, Apalutamide and others), CYP17 inhibitors (including abiraterone acetate, TAK-700, galeterone, ketoconazole, and others), estrogens, Luteinizing Hormone Releasing Hormone (LHRH) agonist/antagonists. Prior therapy with 5α-reductase inhibitors is allowed. LHRH therapy allowed if begun within 4 weeks of day 1.
  2. Prior chemotherapy, radiation therapy, or immunotherapy for prostate cancer.
  3. Prior systemic treatment with an azole drug within two weeks of start of treatment.
  4. Hypogonadism or severe androgen deficiency as defined by screening serum testosterone < 200 ng/dL.
  5. Clinically significant cardiovascular disease within 6 months of study treatment including:

    • Severe or unstable angina;
    • Myocardial infarction;
    • Symptomatic congestive heart failure;
    • New York Heart Association (NYHA) class II-IV heart disease;
    • Arterial or venous thromboembolic events (such as pulmonary embolism cerebrovascular accident including transient ischemic attacks);
    • History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes);
    • Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on screening EKG > 470 msec;
    • History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
    • Uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg). Participants with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy.
  6. History of seizure or any condition or concurrent medication that may predispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect).
  7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Apalutamide, abiraterone acetate, or other study drugs.
  8. Severe hepatic impairment (Child-Pugh Class C).
  9. Active infection (such as human immunodeficiency virus (HIV) or viral hepatitis) or other medical condition that would make prednisone / prednisolone corticosteroid use contraindicated.
  10. History of pituitary or adrenal dysfunction.
  11. Gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
  12. Pre-existing condition that warrants long-term corticosteroid use greater than the equivalent of 10 mg prednisone daily. Physiologic replacement is permitted. Topical, intra-articular, or inhaled corticosteroids are permitted.
  13. Concomitant use of medications that may alter pharmacokinetics of abiraterone acetate or Apalutamide.
  14. Individuals with a history of a different malignancy are ineligible except for the following circumstances: 1) individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy, or 2) individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: non-muscle invasive bladder cancer, basal cell or squamous cell carcinoma of the skin.
  15. Major surgery or radiation therapy within 30 days of screening visit. Participants who have had a major surgery within 30 days of screening visit may be eligible provided the treating investigator deems that the participant is at low risk for complications.
  16. Any condition that in the opinion of the investigator would preclude participation in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02903368


Locations
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United States, California
University of California, San Diego Moores Cancer Center
La Jolla, California, United States, 92093
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Dana-Farber Cancer Institute
Janssen Scientific Affairs, LLC
Investigators
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Principal Investigator: Mary-Ellen Taplin, MD Dana-Farber Cancer Institute

Layout table for additonal information
Responsible Party: Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02903368     History of Changes
Other Study ID Numbers: 16-223
First Posted: September 16, 2016    Key Record Dates
Last Update Posted: May 27, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute:
Prostate Cancer

Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Leuprolide
Abiraterone Acetate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents