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A Study of Androgen Annihilation in High-Risk Biochemically Relapsed Prostate Cancer

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ClinicalTrials.gov Identifier: NCT03009981
Recruitment Status : Recruiting
First Posted : January 4, 2017
Last Update Posted : September 5, 2018
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Alliance Foundation Trials, LLC.

Brief Summary:
This is a randomized, open-label, three-arm, phase 3 study in men with biochemically recurrent prostate cancer and PSA doubling time ≤ 9 months at the time of study entry.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Apalutamide Drug: Degarelix Drug: Abiraterone Acetate Drug: Prednisone Phase 3

Detailed Description:

Patients will be stratified by PSA doubling time (< 3 months vs. 3-9 months) and randomized in 1:1:1 fashion to one of three treatment arms: (1) Control arm consisting of degarelix monotherapy, (2) Experimental arm consisting of apalutamide in combination with degarelix, and (3) Experimental arm consisting of apalutamide, abiraterone acetate + prednisone, and degarelix. Patients will be treated for a maximum duration of 52 weeks and then enter follow up phase until the time of PSA progression, development of metastasis, or patient withdrawal from study, whichever occurs first. Patients with PSA progression will be followed long term until the development of castration resistance, first metastasis, and death.

The primary endpoint of the study is PSA progression-free survival in the intent-to-treat patient population. PSA progression during the 52-week treatment period is defined as a rising PSA confirmed on repeat measurement, and at least 25% and 2 ng/mL above nadir or baseline, whichever is lower. PSA progression during follow up defined as PSA > 0.2 ng/mL confirmed by repeat measurement at least 2 weeks later. Secondary study endpoints include PSA progression-free survival in testosterone-evaluable population, 36-month PSA progression-free survival rate in both intent-to-treat and testosterone-evaluable populations, time to testosterone recovery, time to castration resistance, metastasis-free survival, quality of life, and safety. Each experimental arm will be compared against the control arm in pair-wise fashion. The study is not powered to detect differences in primary or secondary endpoints between the two experimental arms.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 504 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Study of Androgen Annihilation in High-Risk Biochemically Relapsed Prostate Cancer
Actual Study Start Date : March 6, 2017
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Active Comparator: Arm A: Degarelix Monotherapy
Patients randomized to Arm A will receive degarelix subcutaneous injections only.
Drug: Degarelix
Patients randomized to arm A will receive Degarelix every 28 days (+/- 4 days). Patients will receive loading dose of 240 mg (two 120 mg injections) on cycle 1 day 1, followed by maintenance dose of 80 mg subcutaneous injection on day 1 of subsequent cycles. Patients randomized to Arms B or C will receive degarelix at the same schedule in addition to other agents.
Other Name: Firmagon

Experimental: Arm B: Degarelix/Apalutamide
Patients randomized to Arm B will receive degarelix and apalutamide.
Drug: Apalutamide
Patients randomized to Arm B will be instructed to take apalutamide 240 mg (four 60 mg tablets) orally once daily starting on cycle 1 day 1 and continuing throughout 52-week treatment period.

Drug: Degarelix
Patients randomized to arm A will receive Degarelix every 28 days (+/- 4 days). Patients will receive loading dose of 240 mg (two 120 mg injections) on cycle 1 day 1, followed by maintenance dose of 80 mg subcutaneous injection on day 1 of subsequent cycles. Patients randomized to Arms B or C will receive degarelix at the same schedule in addition to other agents.
Other Name: Firmagon

Experimental: Arm C: Degarelix/Apalutamide/Abiraterone/Prednisone
Patients randomized to Arm C will receive degarelix, apalutamide at the same schedule as Arms A/C and will also take abiraterone acetate orally.
Drug: Apalutamide
Patients randomized to Arm B will be instructed to take apalutamide 240 mg (four 60 mg tablets) orally once daily starting on cycle 1 day 1 and continuing throughout 52-week treatment period.

Drug: Degarelix
Patients randomized to arm A will receive Degarelix every 28 days (+/- 4 days). Patients will receive loading dose of 240 mg (two 120 mg injections) on cycle 1 day 1, followed by maintenance dose of 80 mg subcutaneous injection on day 1 of subsequent cycles. Patients randomized to Arms B or C will receive degarelix at the same schedule in addition to other agents.
Other Name: Firmagon

Drug: Abiraterone Acetate
Patients randomized to Arm C will be instructed to take abiraterone acetate 1000 mg (four 250 mg tablets) and prednisone 5mg orally once daily starting on cycle 1 day 1 and continuing throughout 52-week treatment period.
Other Name: Zytiga

Drug: Prednisone
Patients randomized to Arm C will also be instructed to take two prednisone 5 mg tablets daily starting on cycle 1 day 1 and continuing throughout the 52-week treatment period.




Primary Outcome Measures :
  1. PSA progression-free survival [ Time Frame: 36 months ]
    Progression free survival



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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:

  • Histologically confirmed prostate adenocarcinoma
  • Prior radical prostatectomy
  • Biochemically recurrent prostate cancer with PSA doubling time ≤ 9 months at the time of study entry. Calculation of PSA doubling time should include the use of all available PSA values obtained within past 12 months prior to randomization, with a minimum of 3 values separated by at least 2 weeks apart. PSA values obtained prior to localized therapy will be excluded. PSA doubling time to be estimated using Memorial Sloan Kettering Cancer Center online calculator (https://www.mskcc.org/nomograms/prostate/psa-doubling-time)
  • Prior adjuvant or salvage radiation or not a candidate for radiation based upon clinical assessment of disease characteristics and patient co-morbidities.
  • Screening PSA > 0.5 ng/mL
  • No definitive evidence of metastases on screening CT or MRI of abdomen/pelvis and radionuclide whole body bone scan per the judgment of the investigator. Abdominal and/or pelvic lymph nodes measuring 2 cm or less in short axis diameter are allowed. Lesions identified on other imaging modalities (e.g. PSMA or choline PET) that are not visualized on CT and/or MRI or radionuclide bone scan are allowed. Equivocal lesions on bone scan should be followed up with additional imaging as clinically indicated.
  • Screening serum testosterone > 150 ng/dL
  • Eastern Cooperative Oncology Group (ECOG) Performance Status grade 0 or 1
  • Age ≥ 18 years
  • Medications known to lower the seizure threshold (see Appendix 1) must be discontinued or substituted at least 4 weeks prior to study entry.
  • 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.
  • Adequate organ function as defined by the following laboratory values at screening:

    • Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) < 2.5 x upper limit of normal (ULN)
    • Total serum bilirubin ≤1.5 x ULN. 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)
    • Serum potassium ≥ 3.5 mmol/L. Supplementation and re-screening is allowed.
    • Estimated GFR > 45 ml/min using Cockroft-Gault equation
    • Platelets ≥ 100,000/microliter independent of transfusion and/or growth factors within 3 months prior to randomization
    • Hemoglobin ≥ 9.0 g/dL independent of transfusion and/or growth factors within 3 months prior to randomization
    • Serum albumin ≥ 3.0 g/dL

Exclusion Criteria:

  • Prior androgen deprivation therapy and/or first generation anti-androgen (e.g. bicalutamide, nilutamide, flutamide) for biochemically recurrent prostate cancer. Prior ADT and/or first generation anti-androgen in the (neo)adjuvant and/or salvage setting before, during, and/or following radiation or surgery is allowed provided last effective dose of ADT and/or first-generation anti-androgen is > 9 months prior to date of randomization and total duration of prior therapy is ≤ 36 months.
  • Prior treatment with CYP17 inhibitor (e.g. ketoconazole, abiraterone acetate, galeterone) or second generation androgen receptor antagonist including apalutamide or enzalutamide
  • Prior chemotherapy for prostate cancer except if administered in neoadjuvant or adjuvant setting
  • Use of 5-alpha reductase inhibitor within 42 days prior to randomization
  • Use of investigational agent within 28 days prior to randomization
  • Use of other prohibited medications within 7 days prior to cycle 1 day 1 on study (Arms B and C only) (see Appendix 1 for list of prohibited medications)
  • Prior bilateral orchiectomy
  • Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)
  • Uncontrolled hypertension
  • Gastrointestinal disorder affecting absorption or the ability to swallow tablets
  • Baseline severe hepatic impairment (Child-Pugh Class B & C)
  • Intercurrent illness that is not controlled such as active infection, psychiatric illness/social situations that would limit compliance with study requirements
  • Any chronic medical condition requiring a higher dose of corticosteroid than equivalent of 5 mg prednisone/prednisolone once daily

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): NCT03009981


Contacts
Contact: Eunice Aikins-Afful, JD 617-525-8177 AFT19@alliancefoundationtrials.org
Contact: Meryl M Pereji, MS 617-732-7380 AFT19@alliancefoundationtrials.org

  Show 44 Study Locations
Sponsors and Collaborators
Alliance Foundation Trials, LLC.
Janssen Research & Development, LLC
Investigators
Principal Investigator: Monica Bertagnolli, MD Alliance Foundation Trials, LLC.
Study Chair: Rahul Aggarwal, MD University of California, San Francisco

Publications:
Responsible Party: Alliance Foundation Trials, LLC.
ClinicalTrials.gov Identifier: NCT03009981     History of Changes
Other Study ID Numbers: AFT-19
First Posted: January 4, 2017    Key Record Dates
Last Update Posted: September 5, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Alliance Foundation Trials, LLC.:
PSA
Degarelix
Apalutamide
Abiraterone Acetate
Radical Prostatectomy

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