Advanced ChemoHormonal Therapy for Treatment Naive Metastatic Prostate Cancer

OHSU Knight Cancer Institute

Status and phase

Active, not recruiting

Phase 2

Conditions

Castration-Sensitive Prostate Carcinoma

Metastatic Prostate Carcinoma

Stage IVB Prostate Cancer AJCC v8

Treatments

Procedure: Computed Tomography

Drug: Abiraterone Acetate

Drug: Apalutamide

Procedure: Bone Scan

Drug: Antiandrogen Therapy

Other: Questionnaire Administration

Procedure: Biospecimen Collection

Drug: Prednisone

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT04267887

STUDY00016728 (Other Identifier)

NCI-2020-00598 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

III. Molecular changes from prostate cancer over time.

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. Patients undergo computed tomography (CT) scan, bone scan and blood sample collection throughout the study.

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

Enrollment

7 patients

Sex

Male

Ages

18+ years old

Volunteers

No Healthy Volunteers

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
Patients must meet either of the definitions for high risk disease as follows:
- Definition 1: Must have at least 2 of the following 3 at the time diagnosed metastatic:
  - visceral metastatic disease
  - >=3 bone lesions
  - Gleason 8-10 OR
- Definition 2: >=4 bone lesions, including >=1 outside of the vertebral column or pelvis and/or visceral metastatic disease
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 PSA progression or new metastatic deposits since starting ADT; PSA progression is defined as an increase in PSA greater than 25% above nadir, and >2 ng/ml increase confirmed by a second value obtained at least 2 weeks apart
Have completed up to 6 cycles of docetaxel since developing metastatic castration sensitive disease with no more than 16 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
Leukocytes > 3,000/uL
Absolute neutrophil count > 1,500/uL
Platelets >= 100,000 x 10^9/uL, independent of transfusion and/or growth factors
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
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 antiandrogen therapy
- 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
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, 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

7 participants in 1 patient group

Treatment (apalutamide, abiraterone acetate, prednisone, ADT)

Experimental group

Description:

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. Patients undergo CT scan, bone scan and blood sample collection throughout the study.

Treatment: