Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase I Trial of Apalutamide Plus Abiraterone Acetate, Docetaxel, and Prednisone in Patients With mCRPC

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02913196
Recruitment Status : Recruiting
First Posted : September 23, 2016
Last Update Posted : March 12, 2020
Sponsor:
Collaborator:
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Tracking Information
First Submitted Date  ICMJE September 16, 2016
First Posted Date  ICMJE September 23, 2016
Last Update Posted Date March 12, 2020
Study Start Date  ICMJE December 2016
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
Number of participants with dose limiting toxicities (DLT) [ Time Frame: From the time of study drug administration till PSA progression or study completion (~36 months) ]
Dose limiting toxicities will be measured by using the Common Terminology Criteria for Adverse Events or CTCAE version 4.0 which uses a grading scale from 1-5.
Original Primary Outcome Measures  ICMJE
 (submitted: September 21, 2016)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. [ Time Frame: Until PSA progression or study completion (~36 months) ]
Determining a safe dose combination and related toxicities of apalutamide plus abiraterone acetate, docetaxel, prednisone in subjects with mCRPC.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
  • Change in the number of subjects with prostate-specific antigen (PSA) response [ Time Frame: Starting after 12 weeks, at the beginning of Week 4 of combination therapy with docetaxel, apalutamide, abiraterone acetate plus prednisone until PSA progression or study completion (~36 months) ]
  • Change in PSA response [ Time Frame: At the start of treatment until PSA progression or study completion (~36 months) ]
    PSA response will be captured through blood sample collection and radiographic scans
  • Change in the time to PSA progression [ Time Frame: At the start of treatment until PSA progression or study completion (~36 months) ]
    PSA progression will be determined by protocol-specific/modified Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria
  • Change is radiographic progression-free survival [ Time Frame: Images will be collected at baseline, 12 weeks and at end of study, an average of 100 months ]
    Radiographic progression will be determined via scans metric of CT, MRI and Bone scans
  • Change in CellSearch circulating tumor cells (CTC) enumration [ Time Frame: Collected at baseline, 12 weeks and at end of study, an average of 100 months ]
    CTCs will be collected via blood sample collection
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: September 21, 2016)
  • To evaluate exploratory biomarkers predictive of response and resistance in subjects treated with apalutamide in combination with abiraterone acetate, docetaxel plus prednisone [ Time Frame: Until PSA progression or study completion (~36 months) ]
  • To evaluate the antitumor effect of combination therapy with apalutamide, abiraterone acetate, docetaxel and prednisone [ Time Frame: Until PSA progression or study completion (~36 months) ]
 
Descriptive Information
Brief Title  ICMJE Phase I Trial of Apalutamide Plus Abiraterone Acetate, Docetaxel, and Prednisone in Patients With mCRPC
Official Title  ICMJE A Phase I Trial of Apalutamide Plus Abiraterone Acetate, Docetaxel, and Prednisone in Patients With Metastatic Castrate Resistant Prostate Cancer (mCRPC)
Brief Summary

This is a multi-center, Phase I study of apalutamide in combination with abiraterone acetate, docetaxel and prednisone in patients with metastatic mastrate resistant prostate cancer (mCRPC).

This study is designed to determine the dose that apalutamide can be administered safely in combination with abiraterone acetate, docetaxel and prednisone.

Detailed Description

Subjects are enrolled in up to three 3-6-subject cohorts and are administered combination (apalutamide, abiraterone acetate and docetaxel plus prednisone) according to a dose-escalation schedule. The first dose of docetaxel infusion begins on Day 1 Cycle 1. Daily oral apalutamide, abiraterone acetate plus twice-daily oral prednisone begins on Day 1 Cycle 1. Docetaxel 1-hour infusions are administered intravenously every 3 weeks (Q3W), preceded by oral dexamethasone. While a subject is receiving chemotherapy, a treatment cycle is defined as 21 days. Dose limiting toxicity (DLT) determination is based on toxicities observed within the initial 2 cycles defined as 6 weeks. DLT will be assessed before the start of the third docetaxel infusion. Once a combination dose is determined to be safe (i.e. no more than 2 of 6 subjects experience DLT), the next cohort will enroll. Subjects remain at their allocated combination dose until the maximum tolerated dose (MTD) is determined.

The primary objective is to determine a safe dose combination of apalutamide plus abiraterone acetate, docetaxel, prednisone in subjects with mCRPC.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer Metastatic
Intervention  ICMJE
  • Drug: Apalutamide

    Orally available, small molecule, nonsteroidal potent and selective antagonist of the androgen receptor.

    Cohort 1 dose: 120 mg QD Cohort 2 dose: 240 mg QD Cohort 3 dose: 180 mg QD

    Other Name: ARN-509
  • Drug: Abiraterone acetate

    Abiraterone acetate is the prodrug of the active drug abiraterone. Once absorbed after oral administration, abiraterone acetate is rapidly converted to the active form, abiraterone.

    Dose: 1000 mg QD

    Other Name: Zytiga
  • Drug: Docetaxel

    Taxane cytotoxic chemotherapy with demonstrated survival benefit in those with advanced prostate cancer.

    Dose: 75 mg/m2 Q3W

    Other Name: Taxotere
  • Drug: Prednisone
    Dose: 5 mg BID
    Other Name: Deltasone
Study Arms  ICMJE Experimental: All patients
Apalutamide, 120 mg (cohort 1), 240 mg (cohort 2), 180 mg (cohort 3) Abiraterone Acetate 1000mg Prednisone 10mg Docetaxel 75 mg/m2
Interventions:
  • Drug: Apalutamide
  • Drug: Abiraterone acetate
  • Drug: Docetaxel
  • Drug: Prednisone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 21, 2016)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  1. Histologically or cytologically confirmed adenocarcinoma of prostate
  2. Documented progressive metastatic CRPC based on at least one of the following criteria:

    1. PSA progression according to Prostate Cancer Working Group 3 (PCWG3) criteria
    2. Objective radiographic progression in soft tissue, according to modified Response Evaluation Criteria In Solid Tumors (RECIST) or bone scans
  3. ECOG performance status of 0-2
  4. Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy
  5. Age >18 years
  6. Patients must have normal organ and marrow function as defined below:

    1. Absolute neutrophil count >1,500/cells/mm3
    2. Hemoglobin ≥ 9 g/dL
    3. Platelet count >100,000 x 109/microliter
    4. Serum creatinine <1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault
    5. Serum albumin ≥3.2 g/dL
    6. Serum potassium ≥3.5 mmol/L
  7. Patients must be able to take oral medication without crushing, dissolving or chewing tablets
  8. Ability to understand and the willingness to sign a written informed consent document
  9. Medications known to lower the seizure threshold (see list under prohibited medications) must be discontinued or substituted at least 4 weeks prior to study drug initiation
  10. Patients on stable dose of bisphosphonates or RANK-L inhibitor, Denosumab, which have been started no less than 4 weeks prior to treatment start, may continue on this medication

Exclusion Criteria

  1. Liver Function

    1. If total bilirubin is >1.5 x 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 within normal range, subject may be eligible) or
    2. Alanine (ALT) or aspartate (AST) aminotransferase >1.5xULN (or >5xULN for subject with liver metastasis) concomitant with alkaline phosphatase >2.5xULN (or >5xULN for subjects with bone or liver metastases) or
    3. Alanine (ALT or aspartate (AST) aminotransferase >2.5xULN (or >5xULN for subjects with liver metastasis
  2. Use of investigational drugs (including vaccines) or implantation of invasive medical device ≤4 weeks or <5 half-lives of Cycle 1, Day 1 or current enrollment in investigational drug or device study
  3. Prior exposure to apalutamide. Prior exposure to abiraterone acetate and/or other CYP17 inhibitors, enzalutamide is allowed (but not preferred) only during the dose escalation period
  4. Prior chemotherapy for advanced prostate cancer. Prior chemotherapy for any other disease within 3 years
  5. Prior systemic beta-emitting bone-seeking radioisotopes (i.e. strontium-90)
  6. Pre-existing neuropathy ≥Grade 2
  7. Systemic azole treatment (e.g. Fluconazole, itracanozole) ≤2 weeks of Cycle 1 Day 1
  8. Use of potent inducers or inhibitors of CYP3A4 activity ≤2 weeks prior to Day 1 Cycle 1
  9. History of adrenal insufficiency or hyperaldosteronism
  10. Active or symptomatic viral hepatitis
  11. Chronic liver disease
  12. Brain metastases or leptomeningeal disease
  13. Known allergies, hypersensitivity or intolerance to abiraterone acetate, apalutamide, docetaxel, dexamethasone, prednisone, or their excipients
  14. Use of herbal, alternative and food supplements (i.e. PC-Spes, Saw Palmetto, St John Wort, etc) must be discontinued before treatment start. Daily Multi-vitamin, calcium and Vitamin D is allowed
  15. Surgery or local prostatic intervention within 30 days of first dose. [Note: Any clinically relevant sequelae from surgery must have resolved prior to Day 1 Cycle 1]
  16. Radiation therapy for treatment of prostate cancer ≤4 weeks of Day 1 Cycle 1
  17. Current evidence of any of the following:

    1. Uncontrolled hypertension (defined as blood pressure of >150 mmHg systolic and/or >100 mmHg diastolic on medication)
    2. Gastrointestinal disorder affecting absorption
    3. Active infection (e.g., human immunodeficiency virus [HIV] or viral hepatitis) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
    4. Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily
    5. Any condition that in the opinion of the investigator, would preclude participation in this study
    6. Patients with baseline severe hepatic impairment (Child Pugh Class C)
  18. 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 treatment start or New York Heart Association (NYHA) Class II to IV heart disease
  19. Seizure or known condition that may pre-dispose 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)
  20. Having partners of childbearing potential and not willing to use a method of birth control deemed acceptable by the principle investigator and chairperson during the study and for 1 week after last study drug administration
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: GUONC Research Team guonc@med.cornell.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02913196
Other Study ID Numbers  ICMJE 1509016578
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Weill Medical College of Cornell University
Study Sponsor  ICMJE Weill Medical College of Cornell University
Collaborators  ICMJE Janssen Scientific Affairs, LLC
Investigators  ICMJE
Principal Investigator: Scott Tagawa, MD Weill Medical College of Cornell University
PRS Account Weill Medical College of Cornell University
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP