Erdafitinib and Abiraterone Acetate or Enzalutamide in Treating Patients With Double Negative Prostate Cancer
Condition: Castration-Resistant Prostate Carcinoma; Double-Negative Prostate Carcinoma; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Stage IV Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8
MeSH terms: Carcinoma; Prostatic Neoplasms
Intervention: Abiraterone Acetate; Enzalutamide; Erdafitinib
Intervention description: Given PO; Given PO; Given PO
Intervention MeSH terms: Abiraterone Acetate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate

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.
    

Eligibility criteria:

        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)