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Advanced ChemoHormonal Therapy for Treatment Naive Metastatic Prostate Cancer

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ClinicalTrials.gov Identifier: NCT04267887
Recruitment Status : Recruiting
First Posted : February 13, 2020
Last Update Posted : November 6, 2020
Sponsor:
Collaborators:
Janssen Scientific Affairs, LLC
Oregon Health and Science University
Information provided by (Responsible Party):
Julie Graff, OHSU Knight Cancer Institute

Brief Summary:
This phase II trial studies how well the combination of apalutamide, abiraterone acetate, and prednisone after chemotherapy work in treating patients that have received no prior treatment (treatment naive) for high risk prostate cancer that is sensitive to androgen deprivation therapy (castration sensitive) and has spread to other parts of the body (metastatic). This study also aims to understand the inheritance of prostate cancer. If a gene or genes that cause prostate cancer can be found, the diagnosis and treatment of prostate cancer may be improved. Testosterone (a male hormone) can cause the growth of prostate cancer cells. Hormone therapy using apalutamide may fight prostate cancer by blocking the use of testosterone by the tumor cells. Antihormone therapy, such as abiraterone acetate, may lessen the amount of testosterone made by the body. Anti-inflammatory drugs such as prednisone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Apalutamide, abiraterone acetate, and prednisone after chemotherapy may work better in treating patients with castration sensitive prostate cancer.

Condition or disease Intervention/treatment Phase
Castration-Sensitive Prostate Carcinoma Metastatic Prostate Carcinoma Stage IV Prostate Cancer AJCC v8 Stage IVA Prostate Cancer AJCC v8 Stage IVB Prostate Cancer AJCC v8 Drug: Abiraterone Acetate Drug: Antiandrogen Therapy Drug: Apalutamide Drug: Prednisone Other: Quality-of-Life Assessment Other: Questionnaire Administration Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

I. Efficacy of apalutamide in combination with abiraterone acetate + prednisone following docetaxel with ongoing androgen deprivation therapy in men with high risk metastatic castration sensitive disease.

SECONDARY OBJECTIVES:

I. Safety and tolerability of apalutamide in combination with abiraterone acetate + prednisone following docetaxel with ongoing androgen deprivation therapy.

II. Time to event. III. Depth of prostate specific antigen (PSA) response.

EXPLORATORY OBJECTIVES:

I. Quality of life. II. Falls.

OUTLINE:

Patients receive apalutamide orally (PO) once daily (QD), abiraterone acetate PO QD, and prednisone PO QD. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive androgen deprivation therapy per standard of care.

After completion of study treatment, patients are followed up every 6 months for up to 10 years.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 76 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Advanced ChemoHormonal Therapy for Treatment Naïve Metastatic Prostate Cancer: Apalutamide and Abiraterone Acetate With Prednisone and Androgen Deprivation Therapy After Treatment With Docetaxel and Androgen Deprivation Therapy
Actual Study Start Date : May 11, 2020
Estimated Primary Completion Date : January 1, 2024
Estimated Study Completion Date : January 1, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (apalutamide, abiraterone acetate, prednisone, ADT)
Patients receive apalutamide PO QD, abiraterone acetate PO QD, and prednisone PO QD. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive androgen deprivation therapy per standard of care.
Drug: Abiraterone Acetate
Given PO
Other Names:
  • CB7630
  • Yonsa
  • Zytiga

Drug: Antiandrogen Therapy
Given ADT per standard of care
Other Names:
  • ADT
  • Androgen Deprivation Therapy
  • Androgen Deprivation Therapy (ADT)
  • Anti-androgen Therapy
  • Anti-androgen Treatment
  • Antiandrogen Treatment
  • Hormone Deprivation Therapy
  • Hormone-Deprivation Therapy

Drug: Apalutamide
Given PO
Other Names:
  • ARN 509
  • ARN-509
  • ARN509
  • Erleada
  • JNJ 56021927
  • JNJ-56021927

Drug: Prednisone
Given PO
Other Names:
  • .delta.1-Cortisone
  • 1, 2-Dehydrocortisone
  • Adasone
  • Cortancyl
  • Dacortin
  • DeCortin
  • Decortisyl
  • Decorton
  • Delta 1-Cortisone
  • Delta-Dome
  • Deltacortene
  • Deltacortisone
  • Deltadehydrocortisone
  • Deltasone
  • Deltison
  • Deltra
  • Econosone
  • Lisacort
  • Meprosona-F
  • Metacortandracin
  • Meticorten
  • Ofisolona
  • Orasone
  • Panafcort
  • Panasol-S
  • Paracort
  • Perrigo Prednisone
  • PRED
  • Predicor
  • Predicorten
  • Prednicen-M
  • Prednicort
  • Prednidib
  • Prednilonga
  • Predniment
  • Prednisone Intensol
  • Prednisonum
  • Prednitone
  • Promifen
  • Rayos
  • Servisone
  • SK-Prednisone

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Complete prostate specific antigen (PSA) response [ Time Frame: At 12 months from the start of treatment ]
    The complete PSA response is defined as a PSA =< 0.2 ng/ml, confirmed with a 2nd measurement at least 3 weeks later. The estimated PSA response rate will be computed with 95% exact confidence interval. Binomial exact test will be used to determine whether the complete PSA response rate is significantly greater than 43%.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: From day 1 of treatment, assessed up to 10 years ]
    Overall survival will be assessed with each patient visit. After the subject is off active follow up, survival will be assessed by phone.

  2. Incidence of adverse events >= grade 2 [ Time Frame: Up to 10 years ]
    Determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.

  3. Proportion of patients with PSA response >= 50% decrease [ Time Frame: From baseline, assessed up to 12 months ]
    The proportion will be reported with 95% confidence interval.

  4. Proportion of patients with PSA response >= 90% decrease [ Time Frame: From baseline, assessed up to 12 months ]
    The proportion will be reported with 95% confidence interval.

  5. Time to treatment failure [ Time Frame: From start of treatment, assessed up to 10 years ]
    Kaplan-Meier plot will be used to describe the survival distributions.

  6. Time to biochemical (PSA) progression [ Time Frame: From start of treatment, assessed up to 10 years ]
    Kaplan-Meier plot will be used to describe the survival distributions.

  7. Time to radiographic progression [ Time Frame: From start of treatment, assessed up to 10 years ]
    Kaplan-Meier plot will be used to describe the survival distributions.

  8. Time to symptomatic progressive disease [ Time Frame: From start of treatment, assessed up to 10 years ]
    Kaplan-Meier plot will be used to describe the survival distributions.

  9. Time to next therapy for metastatic castration resistant prostate cancer [ Time Frame: From start of treatment, assessed up to 10 years ]
    Kaplan-Meier plot will be used to describe the survival distributions.


Other Outcome Measures:
  1. Change in quality of life (Functional Assessment of Cancer Therapy- Prostate [FACT-P]) scores [ Time Frame: Until end of treatment, up to 10 years ]
    The distribution and change in FACT-P over time will be summarized, and graphically illustrated using spaghetti plot, and tested using mixed effect model.

  2. Number of falls [ Time Frame: Up to 10 years ]
    Reported descriptively.



Information from the National Library of Medicine

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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:

  • Patients must have histologically or cytologically confirmed prostate cancer OR a strong suspicion of prostate cancer as evidenced by metastatic disease in a pattern consistent with prostate cancer (such as blastic lesions on a nuclear medicine bone scan or lymphadenopathy on the computed tomography [CT] scan) AND a PSA > 50 ng/mL
  • High risk disease (defined as meeting 2 of the 3: (1) visceral metastatic disease, (2) 3 or more bone lesions, (3) Gleason 8-10) at the time diagnosed metastatic
  • If a patient has received androgen deprivation therapy (ADT) for neoadjuvant or adjuvant therapy at least 24 months MUST have elapsed since its use to day 1 of restarting ADT for metastatic castration sensitive disease
  • ADT sensitive disease- no evidence of rising PSA or new metastatic deposits since starting ADT
  • Have completed up to 6 cycles of docetaxel since developing metastatic castration sensitive disease with no more than 12 weeks elapsed since day 21 of the final cycle
  • All races and ethnic groups will be included
  • Life expectancy of greater than 18 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Hemoglobin > 9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization
  • Leukocytes > 3,000/uL
  • Absolute neutrophil count > 1,500/uL
  • Platelets >= 100,000 x 10^9/uL, independent of transfusion and/or growth factors within 3 months prior to randomization
  • Total bilirubin =< 1.5 x upper limit of normal (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 =< 1.5 x ULN, subject may be eligible)
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) < 2.5 x institutional upper limit of normal
  • Albumin > 3 g/dL
  • Estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m^2; per Modification of Diet in Renal Disease (MDRD) calculation or institutional standard
  • Serum potassium >= 3.5 mmol/L
  • Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to day 1 of study
  • 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
  • Ability to understand, and the willingness to sign, a written informed consent document, as well as comply with study requirements

Exclusion Criteria:

  • Subjects who are unwilling to stop taking saw palmetto, PC-SPECs or other herbal agents known to affect the PSA
  • Patients may not have received any other investigational agents within 30 days prior to day 1 of study
  • Prior exposure to apalutamide, enzalutamide, abiraterone acetate, darolutamide, or any other second-generation androgen receptor antagonist

    • Note: prior exposure to bicalutamide, flutamide, nilutamide, or any other first-generation androgen receptor antagonist is permitted. No washout is required. Subjects may be on one of these at the time of consent, but it must be stopped prior to day 1 of study treatment. These drugs are frequently used in the newly diagnosed metastatic setting to blunt the effect of the testosterone spike
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to apalutamide or other agents used in the study
  • Conditions that would interfere with treatment with docetaxel chemotherapy in the opinion of the treating physician (e.g. significant neuropathy)
  • Subject has another active malignancy other than non-melanomatous skin cancer (unless it is metastatic) or superficial bladder cancer
  • Either of the following:

    • Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)
    • Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure or left ventricular ejection fraction < 50%, 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 day 1 of study
  • Current evidence of any of the following:

    • Uncontrolled hypertension
    • Gastrointestinal disorder affecting absorption
    • Active infection (e.g. human immunodeficiency virus [HIV] or viral hepatitis)
    • Any chronic medical condition requiring a higher dose of corticosteroid than a total of 10 mg prednisone/prednisolone daily
    • Any condition that in the opinion of the investigator, would preclude participation in this study.
    • Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment. If a strong CYP3A4 inducer must be co-administered, increase the abiraterone acetate dosing frequency to twice a day only during the co-administration period (e.g., from 1,000 mg once daily to 1,000 mg twice a day).
    • 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
    • Baseline moderate and severe hepatic impairment (Child Pugh Class B & C)
  • Inability to stop a prohibited medication:

    • Atypical antipsychotics (e.g. clozapine, olanzapine, risperidone, ziprasidone)
    • Bupropion
    • Lithium
    • Meperidine and pethidine
    • Phenothiazine antipsychotics (e.g. chlorpromazine, mesoridazine, thioridazine)
    • Tricyclic antidepressants (e.g. amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine
    • Tramadol

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): NCT04267887


Locations
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United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Shawna Bailey    503-418-9104    bailesh@ohsu.edu   
Principal Investigator: Julie N. Graff         
Sponsors and Collaborators
OHSU Knight Cancer Institute
Janssen Scientific Affairs, LLC
Oregon Health and Science University
Investigators
Layout table for investigator information
Principal Investigator: Julie N Graff OHSU Knight Cancer Institute
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Responsible Party: Julie Graff, Principal Investigator, OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT04267887    
Other Study ID Numbers: STUDY00016728
NCI-2020-00598 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
STUDY00016728 ( Other Identifier: OHSU Knight Cancer Institute )
First Posted: February 13, 2020    Key Record Dates
Last Update Posted: November 6, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Prostatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Prostatic Diseases
Ascorbic Acid
Prednisone
Cortisone
Methyltestosterone
Abiraterone Acetate
Hormones
Estrogens, Conjugated (USP)
Androgens
Androgen Antagonists
Anti-Inflammatory Agents
Glucocorticoids
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
Antioxidants