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

NCT03999515 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: RG1005038NCI-2019-0381210288
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Prostate

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 67 days

Secondary Outcomes (5)

• Radiographic Progression Free Survival (PFS)

  Up to 67 days

• Time to Response

  Up to 67 days

• Overall Survival (OS)

  From cycle 1, day 1 to the date of death, assessed up to 178 days

• Prostate-specific Antigen (PSA) Response

  Baseline up to 73 days

• Incidence and Severity of Adverse Events (AEs)

  Within 14 days of end of treatment, an average of 1 year.

Study Arms (1)

Treatment (abiraterone acetate, enzalutamide, erdafitinib)

EXPERIMENTAL

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.

Drug: Abiraterone Acetate; Drug: Enzalutamide; Drug: Erdafitinib

Interventions

Abiraterone Acetate DRUG

Given PO

Also known as: 154229-18-2, 17-(3-Pyridyl)-5, 16-androstadien-3beta-acetate, Androsta-5,16-dien-3-ol, 17-(3-pyridinyl)-, acetate (ester), CB7630, Yonsa, Zytiga, BR9004, BR9004-1, JNJ-212082

Treatment (abiraterone acetate, enzalutamide, erdafitinib)

Enzalutamide DRUG

Given PO

Also known as: 915087-33-1, ASP9785, Benzamide, MDV3100, Xtandi

Treatment (abiraterone acetate, enzalutamide, erdafitinib)

Erdafitinib DRUG

Given PO

Also known as: Balversa, JNJ-42756493

Treatment (abiraterone acetate, enzalutamide, erdafitinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; Acetates; Esters; enzalutamide; benzamide; erdafitinib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Results Point of Contact

• Title: Dr. Michael Schweizer
• Organization: Fred Hutchinson Cancer Center

mtschwei@fredhutch.org

2066066252

Study Officials

• Michael Schweizer

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 21, 2019
• First Posted: June 26, 2019
• Study Start: April 27, 2020
• Primary Completion: June 6, 2021
• Study Completion: June 6, 2021
• Last Updated: September 28, 2023
• Results First Posted: September 28, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)