Clinical Trials /

Erdafitinib and Abiraterone Acetate or Enzalutamide in Treating Patients With Double Negative Prostate Cancer

NCT03999515

Description:

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. Drugs, such as abiraterone acetate, may lessen the amount of testosterone made by the body. Drugs used in chemotherapy, such as enzalutamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving erdafitinib with abiraterone acetate or enzalutamide may work better in treating patients with prostate cancer compared to abiraterone acetate or enzalutamide alone.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Erdafitinib and Abiraterone Acetate or Enzalutamide in Treating Patients With Double Negative Prostate Cancer
  • Official Title: Erdafitinib Plus Abiraterone Acetate or Enzalutamide in Double Negative Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: RG1005038
  • SECONDARY ID: NCI-2019-03812
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT03999515

Conditions

  • Castration Levels of Testosterone
  • Castration-Resistant Prostate Carcinoma
  • Double-Negative Prostate Carcinoma
  • Metastatic Prostate Carcinoma
  • Prostate Adenocarcinoma
  • PSA Progression
  • Stage IV Prostate Cancer AJCC v8
  • Stage IVA Prostate Cancer AJCC v8
  • Stage IVB Prostate Cancer AJCC v8

Interventions

DrugSynonymsArms
Abiraterone Acetate154229-18-2, 17-(3-Pyridyl)-5, 16-androstadien-3beta-acetate, Androsta-5,16-dien-3-ol, 17-(3-pyridinyl)-, acetate (ester), CB7630, Yonsa, ZytigaTreatment (abiraterone acetate, enzalutamide, erdafitinib)
Abiraterone154229-19-3, 17-(3-Pyridyl)androsta-5, 16-dien-3beta-ol, CB 7598Treatment (abiraterone acetate, enzalutamide, erdafitinib)
Enzalutamide915087-33-1, ASP9785, Benzamide, MDV3100, XtandiTreatment (abiraterone acetate, enzalutamide, erdafitinib)
ErdafitinibBalversa, JNJ-42756493Treatment (abiraterone acetate, enzalutamide, erdafitinib)

Purpose

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. Drugs, such as abiraterone acetate, may lessen the amount of testosterone made by the body. Drugs used in chemotherapy, such as enzalutamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (abiraterone acetate, enzalutamide, erdafitinib)ExperimentalPatients 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
  • Abiraterone
  • Enzalutamide
  • Erdafitinib

Eligibility Criteria

        Inclusion Criteria:

          -  History of histologically diagnosed prostatic adenocarcinoma

          -  Participants must have evidence of castration resistant prostate cancer as evidenced
             by a confirmed rising PSA (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 both abiraterone acetate and
             enzalutamide, with PSA or clinical/radiographic progression on the most recent agent
             per PCWG3 criteria. There should be no washout of the most recent agent received (i.e.
             abiraterone acetate or enzalutamide) prior to initiating erdafitinib per protocol

          -  Measurable disease as defined per RECIST v1.1 criteria

          -  Subjects must have evidence of double-negative prostate cancer as defined by
             immunohistochemistry

          -  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 (in which case direct bilirubin =< 1.5 x ULN is required)

          -  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 predominate small cell or neuroendocrine variant prostate cancer on
             standard of care metastatic biopsy within the past 8 weeks prior to signing consent

          -  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

          -  Any corneal or retinal abnormality likely to increase the risk of eye toxicity or lens
             conditions, such as untreated mature or hypermature senile cataract, affecting visual
             acuity that impair the ability to interpret the Amsler grid test, i.e.:

               -  History of or current evidence of central serous retinopathy (CSR) or retinal
                  vascular occlusion (RVO)

               -  Active wet, age-related macular degeneration (AMD)

               -  Diabetic retinopathy with macular edema (non-proliferative)

               -  Uncontrolled glaucoma (per local standard of care)

               -  Corneal pathology such as keratitis, keratoconjunctivitis, keratopathy, corneal
                  abrasion, inflammation or ulceration

          -  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, require immediate treatment
             (e.g. those with extensive liver metastases)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate
Time Frame:Up to 2 years
Safety Issue:
Description: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 Outcome Measures

Measure:Radiographic progression free survival (PFS)
Time Frame:Up to 2 years
Safety Issue:
Description:Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for soft tissue metastases and Prostate Cancer Working Group 3 criteria for bone metastases. Will be presented with Kaplan-Meier curves, and the median survival with 95% confidence interval (CI) will be calculated. Rates will be reported as percentages with 95% CI.
Measure:Time to response
Time Frame:Up to 2 years
Safety Issue:
Description:Will be assessed by RECIST 1.1.
Measure:Overall survival (OS)
Time Frame:Up to 2 years
Safety Issue:
Description:Will be assessed by RECIST 1.1. Will be presented with Kaplan-Meier curves, and the median survival with 95% CI will be calculated. Rates will be reported as percentages with 95% CI.
Measure:Prostate-specific antigen (PSA) response
Time Frame:Baseline up to 2 years
Safety Issue:
Description:PSA response will be defined by a > 50% reduction in PSA compared with baseline at any point during treatment.
Measure:Incidence and severity of adverse events (AEs)
Time Frame:Within 14 days of end of treatment
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Washington

Trial Keywords

  • Prostate

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