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Apalutamide and Abiraterone Acetate in African American and Caucasian Men With Metastatic Castrate Resistant Prostate Cancer (PANTHER)

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ClinicalTrials.gov Identifier: NCT03098836
Recruitment Status : Recruiting
First Posted : April 4, 2017
Last Update Posted : June 7, 2018
Sponsor:
Collaborator:
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
Daniel George, MD, Duke University

Brief Summary:

The primary goal is to prospectively estimate the median PFS of African American and Caucasian men with mCRPC taking apalutamide, abiraterone acetate, and prednisone. Secondary objectives include: PSA kinetics: to determine the duration of PSA response, time to nadir, and percent of men who achieve a PSA < 0.1; Radiographic assessments: to estimate the rate of objective response and incidence of bone flares; Safety (NCI CTC v4.0) and tolerability, particularly incidence and grade of hypertension in the two populations.

This is a non-comparative pilot open-label, parallel arm, multicenter study of apalutamide and abiraterone acetate in African American and Caucasian men with mCRPC. It is anticipated that 3 additional sites will be needed to accrue 100 subjects (50 African American and 50 Caucasian) over a 24 month accrual period. The study agents will be administerd at the following doses: apalutamide 240mg orally once daily, abiraterone acetate 1000mg orally once daily, and prednisone 5 mg BID in 4-week cycles throughout the treatment period.

Fifty (50) patients will be enrolled in each group (AA and Caucasians). The proportion of patients who experience PSA decline of 30%, 50% and 90% will be estimated with exact 95% confidence intervals based on the binomial distribution will be computed. In addition, post therapy changes in PSA will be explored as a continuous outcome. The Kaplan-Meier product limit method will be used to estimate the rPFS, biochemical PFS and overall survival distributions.


Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: ARN-509 Drug: Abiraterone Acetate Drug: Prednisone Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Study of Apalutamide and Abiraterone Acetate iN ChemoTHerapy-Naïve mEn With mCRPC Stratified by Race
Actual Study Start Date : July 10, 2017
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : June 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Caucasian Drug: ARN-509
240 mg orally daily
Other Name: apalutamide

Drug: Abiraterone Acetate
1000 mg orally daily
Other Name: Zytiga

Drug: Prednisone
5 mg orally twice daily (for total daily dose 10 mg)

Experimental: African American Drug: ARN-509
240 mg orally daily
Other Name: apalutamide

Drug: Abiraterone Acetate
1000 mg orally daily
Other Name: Zytiga

Drug: Prednisone
5 mg orally twice daily (for total daily dose 10 mg)




Primary Outcome Measures :
  1. Median radiographic progression free survival (PFS) [ Time Frame: every 12 weeks, up to 2 years ]
    Radiographic PFS based on PCWG2 criteria or based on the onset of a skeletal related event. Imaging obtained every 12 weeks.


Secondary Outcome Measures :
  1. Change in PSA response [ Time Frame: every 4 weeks, up to 2 years ]
    Duration of PSA response

  2. Time to PSA nadir [ Time Frame: every 4 weeks, up to 2 years ]
    Time to PSA nadir

  3. Percent of men who achieve a PSA < 0.1 [ Time Frame: every 4 weeks, up to 2 years ]
    Percent of men who achieve a PSA < 0.1

  4. Change in radiologic response rates [ Time Frame: every 12 weeks, up to 2 years ]
    RECIST 1.1 defined radiologic response rates and incidence of bone flares

  5. Number of adverse events [ Time Frame: up to 2 years ]
    Safety (NCI CTC v4.0) and tolerability, particularly incidence and grade of hypertension in the two populations

  6. Overall survival [ Time Frame: every 6 months, up to 3 years ]
    Survival of subjects over the time the study is ongoing



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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, age ≥ 18 years
  2. Karnofsky performance status ≥ 70 (Appendix 1)
  3. Life expectancy of ≥ 12 months as determined by treating investigator
  4. Written Authorization for Use and Release of Health and Research Study Information (HIPAA authorization per institutional requirements)
  5. Willing/able to adhere to the prohibitions and restrictions specified in this protocol
  6. Willing to take abiraterone acetate on an empty stomach, and should be able to swallow tablets whole, without crushing/chewing tablets. Must have the ability to swallow, retain, and absorb oral medication.
  7. Medications known to lower the seizure threshold (see list under prohibited meds, appendix 2) must be discontinued or substituted at least 4 weeks prior to study entry
  8. Agrees 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 agrees 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. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug. Abstinence is an acceptable method of birth control.
  9. Adequate bone marrow function as shown by: ANC ≥ 1.0 x 109/L, Platelets ≥ 100 x 109/L, Hb≥9 g/dL, (independent of transfusion and/or growth factors within 3 months prior to Cycle 1 Day 1)
  10. Serum potassium ≥ 3.5 mEq/L
  11. Serum albumin of ≥ 3.0 g/dl
  12. AST/SGOT and ALT/SGPT <2.5 x Institutional Upper Limit of Normal (ULN)
  13. Serum total bilirubin ≤ 1.5 x Institutional ULN (Note: In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)
  14. GFR ≥45 mL/min
  15. Histologically confirmed diagnosis of adenocarcinoma of the prostate. Histologic variants of prostate cancer comprising of >50% of the tumor including neuroendocrine features and small cell carcinoma of the prostate are excluded.
  16. Radiographic evidence of metastatic disease based on RECIST 1.1 Criteria OR by prostate cancer-specific PET imaging. Evaluable non-target lesions and/or bone only metastasis are permitted per RECIST 1.1 and PCWG3 guidelines. Non-target, pathological lymph nodes ≥ 10 mm and less than 15 mm in the short axis are permitted.
  17. Ongoing ADT using an LHRH agonist (e.g. leuprolide, goserelin) or antagonist (e.g. degarelix) must continue on therapy unless prior bilateral orchiectomy has been performed.
  18. PSA ≥ 2.0 ng/mL
  19. Evidence of castration resistant disease in the setting of ongoing ADT (medical or surgical) as evidenced by one of the following:

    • Absolute rise in PSA of 2.0 ng/mL or an increase >25% from the nadir, minimum 2 consecutive rising PSA levels with an interval of ≥ 1 week between each PSA level, OR
    • CT or MRI based evidence of disease progression (soft tissue, nodal or visceral disease progression) according to PCWG3 criteria or RECIST 1.1 criteria, OR
    • At least 1 new bone scan lesion as compared to the most immediate prior radiologic studies.
  20. A minimum of 2 weeks elapsed off of antiandrogen therapy prior to start of study drug (i.e. flutamide, nilutamide, bicalutamide.)
  21. A minimum of 2 weeks elapsed off of sipuleucel-T and radiation therapy prior to start of study drug
  22. A minimum of 4 weeks from any major surgery prior to start of study drug.
  23. Self-reported race of either African American or Caucasian.
  24. Ability to understand and the willingness to sign a written informed consent document. If the subject is unable to understand the consent due to comorbidity, such as Alzheimer's disease, consent by a legally authorized representative and assent by the subject will be obtained.

Exclusion Criteria:

  1. Prior treatment with abiraterone acetate, enzalutamide, apalutamide (ARN-509), galaterone (TOK-001), orteronel (TAK-700), or similar agent
  2. Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
  3. Active or symptomatic infection including HIV, viral hepatitis or chronic liver disease
  4. Any chronic medical condition requiring a higher dose of corticosteroid than 5mg prednisone/prednisolone bid
  5. Have known allergies, hypersensitivity, or intolerance to abiraterone acetate, apalutamide or prednisone or their excipients.
  6. Pathological finding consistent with small cell carcinoma of the prostate
  7. Symptomatic liver or visceral organ metastasis
  8. Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents
  9. Known brain metastasis
  10. Prior cytotoxic chemotherapy or biologic therapy for the treatment of CRPC. Note: sipulecel-T is permitted with a 2-week washout.
  11. Previously treated with ketoconazole for prostate cancer for greater than 7 days
  12. Prior systemic treatment with an azole anti-fungal drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1.
  13. Uncontrolled hypertension (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
  14. Poorly controlled diabetes, FBS ≥200 mg/dL
  15. History of pituitary or adrenal dysfunction
  16. Symptomatic Atrial Fibrillation, or other symptomatic cardiac arrhythmia
  17. Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of recurrence within 24 months
  18. History of any of the following:

    • Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 6 months of Cycle 1 Day 1, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)
    • Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to first dose of study drug. Venous thrombolic events within 6 months are permitted IF they are not attributed to prostate cancer (in the opinion of the treating physician).
  19. Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment.
  20. 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
  21. Baseline moderate or severe hepatic impairment (Child Pugh Class B & C)
  22. Use of herbal products that may decrease PSA levels (i.e., saw palmetto) refer to section 8.3.2 (no washout period required)
  23. Administration of an investigational therapeutic within 30 days prior to Cycle 1, Day 1
  24. Any condition which, in the opinion of the investigator, would preclude participation in this trial

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): NCT03098836


Contacts
Contact: Julia Rasmussen, MS, BSN 919-681-1030 julia.rasmussen@duke.edu

Locations
United States, North Carolina
Duke Cancer Center Cary Recruiting
Cary, North Carolina, United States, 27518
Contact: Kellie Shobe, RN       kellie.shobe@duke.edu   
Contact: Donna Allen, RN       donna.allen@duke.edu   
Principal Investigator: William R. Berry, MD         
Novant Health Presbyterian Medical Center Recruiting
Charlotte, North Carolina, United States, 28204
Contact: Nicole Nechiporchik       nnechiporchik@novanthealth.org   
Principal Investigator: Deborah A Bradley, MD         
Johnston Hematology and Oncology of Clayton Recruiting
Clayton, North Carolina, United States, 27520
Contact: Kim Ward, RN    919-419-5410    kim.ward@duke.edu   
Principal Investigator: Daniel George, MD         
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Kelly O Onyenwoke, RN    919-681-1030    kelly.o.onyenwoke@duke.edu   
Principal Investigator: Daniel George, MD         
Maria Parham Hospital Recruiting
Henderson, North Carolina, United States, 27536
Contact: Kim Ward, RN    919-419-5410    kim.ward@duke.edu   
Principal Investigator: Daniel George, MD         
Scotland Memorial Hospital Recruiting
Laurinburg, North Carolina, United States, 28352
Contact: Kim Ward, RN    919-419-5410    kim.ward@duke.edu   
Principal Investigator: Daniel George, MD         
Southeastern Regional Recruiting
Lumberton, North Carolina, United States, 28358
Contact: Kim Ward, RN    919-419-5410    kim.ward@duke.edu   
Principal Investigator: Daniel George, MD         
Johnston Memorial Hospital Recruiting
Smithfield, North Carolina, United States, 27577
Contact: Kim Ward, RN    919-419-5410    Kim.ward@duke.edu   
Principal Investigator: Daniel George, MD         
Novant Health Presbyterian Medical Center Recruiting
Winston-Salem, North Carolina, United States, 27103
Contact: Nicole Nechiporchik       nnechiporchik@novanthealth.org   
Principal Investigator: Deborah A Bradley, MD         
United States, South Carolina
Spartanburg Regional Recruiting
Spartanburg, South Carolina, United States, 29303
Contact: Christy Moore, RN    864-560-1033    cmoore@gibbscc.org   
United States, Virginia
Virginia Oncology Associates Recruiting
Hampton, Virginia, United States, 29303
Contact: Elaine Colon, BS, CCRP    757-262-4633    Elaine.colon@usoncology.com   
Virginia Oncology Associates Recruiting
Norfolk, Virginia, United States, 23502
Contact: Elaine Colon         
Contact    757-262-4633    elaine.colon@usoncology.com   
Sponsors and Collaborators
Daniel George, MD
Janssen Scientific Affairs, LLC
Investigators
Principal Investigator: Daniel J. George, MD Duke Cancer Institute

Responsible Party: Daniel George, MD, Professor, Duke University
ClinicalTrials.gov Identifier: NCT03098836     History of Changes
Other Study ID Numbers: Pro00075097
First Posted: April 4, 2017    Key Record Dates
Last Update Posted: June 7, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daniel George, MD, Duke University:
metastatic
castrate resistant

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
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