Castration-Resistant Prostate Carcinoma, Double-Negative Prostate Carcinoma, Metastatic Prostate Carcinoma, Prostate Adenocarcinoma, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Stage IV Prostate Cancer AJCC v8
Conditions
Keywords
Prostate
Brief summary
This phase II trial studies how well erdafitinib in combination with abiraterone acetate or enzalutamide works in treating patients with double negative prostate cancer. Erdafitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Testosterone can cause the growth of prostate cancer cells. Abiraterone acetate lowers the amount of testosterone made by the body. This may help stop the growth of tumor cells that need testosterone to grow. Enzalutamide blocks the use of testosterone by the tumor cells. Giving erdafitinib with abiraterone acetate or enzalutamide may work better in treating patients with prostate cancer compared to abiraterone acetate or enzalutamide alone.
Detailed description
OUTLINE: Patients receive abiraterone acetate orally (PO) once daily (QD) or enzalutamide PO QD on days 1-21. Patients also receive erdafitinib PO QD on days 1-21. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.
Interventions
DRUGAbiraterone Acetate
Given PO
DRUGEnzalutamide
Given PO
DRUGErdafitinib
Given PO
Sponsors
Janssen Research & Development, LLC
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must be \>= 18 years of age prior to signing informed consent * History of histologically diagnosed prostatic adenocarcinoma * Participants must have evidence of castration resistant prostate cancer as evidenced by a confirmed rising PSA or radiographic progression (per Prostate Cancer Working Group 3 \[PCWG3\] criteria) and a castrate serum testosterone level (i.e. =\< 50 mg/dL) * Participants must have previously progressed on abiraterone acetate and/or enzalutamide, with PSA or radiographic progression on the most recent agent per PCWG3 criteria. If the most recent agent received was abiraterone or enzalutamide there should be no washout prior to initiating erdafitinib per protocol * Measurable disease as defined per RECIST v1.1 criteria * Subjects who have progressed on only one next-generation AR-directed therapy (e.g. abiraterone, enzalutamide) and who have not received taxane chemotherapy will be required to have evidence of double-negative prostate cancer as defined by immunohistochemistry on biopsy. A fresh metastatic biopsy within 8 weeks is preferred; however, any archival tissue showing a DNPC phenotype will be acceptable for determining eligibility. Patients who have received two prior lines of AR-directed therapy and at least one prior taxane do not require histologic confirmation of DNPC. Note: transcript profiling methods for defining DNPC may be accepted per the PI's discretion * Eastern Cooperative Oncology Group (ECOG) performance status score =\< 2 * Hemoglobin \>= 8 g/dL (\>= 5 mmol/L) (must be without red blood cell \[RBC\] transfusion within 7 days prior to the laboratory test) * Platelets \>= 75 x 10\^9/L * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (prior growth factor support is permitted but must be without support in the 7 days prior to the laboratory test) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN) or =\< 5 x ULN for subjects with liver metastases * Creatinine clearance \>= 40 mL/min/1.73 m\^2 based upon modified diet in renal disease formula calculation * Total bilirubin =\< 1.5 x ULN; except in subjects with congenital bilirubinemia, such as Gilbert syndrome * Corrected QT interval (corrected QT interval by Fridericia \[QTcF\] or QT corrected interval by the Bazett's formula \[QTcB\]) =\< 480 msec based on the average of triplicate assessments performed approximately 5 minutes apart * Subjects must agree to use acceptable contraception * Must sign an informed consent form (ICF) (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
Exclusion criteria
* Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 14 days prior to randomization * Active malignancies (i.e., requiring treatment change in the last 24 months) other than malignancy under study (except skin cancers within the last 24 months that is considered completely cured) * Evidence of predominant small cell or neuroendocrine variant prostate cancer on most recent standard of care metastatic biopsy * Symptomatic central nervous system (CNS) metastases. Treated CNS metastases will be allowed if these are stable for at least 8 weeks prior to enrollment * Received prior FGFR inhibitor treatment or if the subject has known allergies, hypersensitivity, or intolerance to erdafitinib or its excipients * Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade * Has persistent phosphate level \> ULN during screening (on 2 consecutive assessments at least 1 week apart, within 14 days of treatment and prior to cycle 1 day 1) and despite medical management * Has a history of or current uncontrolled cardiovascular disease including: * Unstable angina, myocardial infarction, ventricular fibrillation, Torsades de Pointes, cardiac arrest, or known congestive heart failure class III-V within the preceding 3 months; cerebrovascular accident or transient ischemic attack within the preceding 3 months * Pulmonary embolism or other VTE (venous thromboembolism) within the preceding 2 months * Has known active acquired immune deficiency syndrome (AIDS) (human immunodeficiency virus \[HIV\] infection) * Hepatitis B infection as defined according to the American Society of Clinical Oncology guidelines. In the event the infection status is unclear, quantitative levels are necessary to determine the infection status. Hepatitis C (anti-hepatitis C virus \[HCV\] antibody positive or HCV-ribonucleic acid \[RNA\] quantitation positive) or known to have a history of hepatitis C. If positive, further testing of quantitative levels to rule out positivity is required * Has not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration, hot flashes, grade 1 neuropathy, grade 1-2 hearing loss) * Has impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions * Major surgery within 2 weeks of the first dose, or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study or within 2 weeks after the last dose of study drug administration. (Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate * Any serious underlying medical condition, such as: * Evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection * Active autoimmune disease or a documented history of autoimmune disease * Psychiatric conditions (e.g., alcohol or drug abuse), dementia, or altered mental status * Any other issue that would impair the ability of the subject to receive or tolerate the planned treatment at the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments * Patient, who, in the opinion of their treating physician, requires immediate treatment (e.g. those with extensive liver metastases)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Up to 67 days | Will be calculated as the percentage of patients, with 95% confidence intervals, achieving a complete response or partial response across the entire study population at any time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Progression Free Survival (PFS) | Up to 67 days | Progression free survival is time to progressive disease. Disease progression is determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for soft tissue metastases and Prostate Cancer Working Group 3 criteria for bone metastases. Median progression free survival will be calculated. |
| Time to Response | Up to 67 days | Time to response is the time until a radiographic response occures as determined by RECIST 1.1 criteria. This cannot be determined since only two patients had re-staging scans on study and neither had a response. |
| Overall Survival (OS) | From cycle 1, day 1 to the date of death, assessed up to 178 days | Overall survival is time to death from any cause. Median overall survival survival will be calculated. |
| Prostate-specific Antigen (PSA) Response | Baseline up to 73 days | PSA response will be defined by a \> 50% reduction in PSA compared with baseline at any point during treatment. We will report the percentage of patients who achieve a PSA response. |
| Incidence and Severity of Adverse Events (AEs) | Within 14 days of end of treatment, an average of 1 year. | Will be assessed using version National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will characterize AEs by type and grade. Safety will be summarized as the severity and frequency of a given AE. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Abiraterone Acetate, Enzalutamide, Erdafitinib) Patients receive abiraterone acetate orally PO QD or enzalutamide PO QD on days 1-21. Patients also receive erdafitinib PO QD on days 1-21. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity.
Abiraterone Acetate: Given PO
Enzalutamide: Given PO
Erdafitinib: Given PO | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Treatment (Abiraterone Acetate, Enzalutamide, Erdafitinib) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Race/Ethnicity, Customized White, Non Hispanic | 3 Participants |
| Region of Enrollment United States | 3 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 |
Outcome results
Primary
Objective Response Rate
Will be calculated as the percentage of patients, with 95% confidence intervals, achieving a complete response or partial response across the entire study population at any time.
Time frame: Up to 67 days
Population: Enrolled patients who had re-staging scans performed. Note, study was terminated early due to low accrual.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Abiraterone Acetate, Enzalutamide, Erdafitinib) | Objective Response Rate | 0 Participants |
Secondary
Incidence and Severity of Adverse Events (AEs)
Will be assessed using version National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will characterize AEs by type and grade. Safety will be summarized as the severity and frequency of a given AE.
Time frame: Within 14 days of end of treatment, an average of 1 year.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Abiraterone Acetate, Enzalutamide, Erdafitinib) | Incidence and Severity of Adverse Events (AEs) | 3 Participants |
Secondary
Overall Survival (OS)
Overall survival is time to death from any cause. Median overall survival survival will be calculated.
Time frame: From cycle 1, day 1 to the date of death, assessed up to 178 days
Population: Note, study was terminated early due to low accrual.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Abiraterone Acetate, Enzalutamide, Erdafitinib) | Overall Survival (OS) | 94 days |
Secondary
Prostate-specific Antigen (PSA) Response
PSA response will be defined by a \> 50% reduction in PSA compared with baseline at any point during treatment. We will report the percentage of patients who achieve a PSA response.
Time frame: Baseline up to 73 days
Population: Enrolled patients who had repeat PSA performed while on study. Note, study was terminated early due to low accrual.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Abiraterone Acetate, Enzalutamide, Erdafitinib) | Prostate-specific Antigen (PSA) Response | 0 Participants |
Secondary
Radiographic Progression Free Survival (PFS)
Progression free survival is time to progressive disease. Disease progression is determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for soft tissue metastases and Prostate Cancer Working Group 3 criteria for bone metastases. Median progression free survival will be calculated.
Time frame: Up to 67 days
Population: Enrolled patients who had re-staging scans performed. Note, study was terminated early due to low accrual.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Abiraterone Acetate, Enzalutamide, Erdafitinib) | Radiographic Progression Free Survival (PFS) | 59 days |
Secondary
Time to Response
Time to response is the time until a radiographic response occures as determined by RECIST 1.1 criteria. This cannot be determined since only two patients had re-staging scans on study and neither had a response.
Time frame: Up to 67 days
Population: Enrolled patients who had re-staging scans performed. Note, study was terminated early due to low accrual.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Abiraterone Acetate, Enzalutamide, Erdafitinib) | Time to Response | NA years |