A Study of Erdafitinib in Castration-Resistant Prostate Cancer Patients Evaluating Markers of Bone Remodeling and FGF Signaling in Plasma and Bone Marrow
Overview
- Phase
- Phase 2
- Intervention
- Biopsy
- Conditions
- Castration-Resistant Prostate Carcinoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 11
- Locations
- 1
- Primary Endpoint
- Bone specific alkaline phosphatase (BAP) modulation
- Status
- Terminated
- Last Updated
- 2 months ago
Overview
Brief Summary
This phase II trial studies the effect of erdafitinib in treating patients with prostate cancer that grows and continues to spread despite the surgical removal of the testes or drugs to block androgen production (castration-resistant). Erdafitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erdafitinib may help control disease in patients with castration-resistant prostate cancer. In addition, studying samples of blood, tissue, plasma, and bone marrow from patients with castration-resistant prostate cancer in the laboratory may help doctors learn more about changes that occur in deoxyribonucleic acid (DNA) and identify biomarkers related to cancer.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate efficacy of erdafitinib in subjects with advanced prostate cancer who have progressed on a second-generation androgen receptor (AR)-targeting agents (SART). SECONDARY OBJECTIVES: I. To evaluate the objective response rate II. To measure Time on Treatment (ToT) as a surrogate of clinical efficacy and Progression-Free Survival (PFS) III. To measure PFS. IV. To correlate bone specific alkaline phosphatase (BAP) modulation with response, ToT and PFS. V. To correlate prostate specific antigen (PSA) modulation with response, ToT and PFS. VI. To characterize the safety profile of subjects treated with erdafitinib. VII. To measure overall survival. VIII. To collect and archive bone marrow biopsies and aspirates, serum and plasma in study patients for later hypothesis generating associations. EXPLORATORY OBJECTIVE: I. To evaluate DNA, ribonucleic acid (RNA), or protein biomarkers in tissue and blood samples which potentially predict tumor response or resistance to erdafitinib. OUTLINE: Patients receive erdafitinib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may also undergo collection of blood and bone marrow via biopsy and aspirates. After completion of study treatment, patients are followed up at 30 days, every 16 weeks for 1 year, and then every 6 months thereafter.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age \>= 18 years
- •Histologically proven adenocarcinoma or small cell of the prostate with evidence for skeletal metastases on bone scan and/or computed tomography (CT)/positron emission tomography (PET)/magnetic resonance imaging (MRI) scan. Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
- •Serum testosterone levels =\< 50 ng/ml and maintenance of castration with luteinizing hormone-releasing hormone (LHRH) agonist/antagonist or orchiectomy
- •Patients must have documented evidence of progressive disease as defined by any of the following:
- •PSA progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least \>= 1.0 ng/mL
- •New or increasing non-bone disease (Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria)
- •Positive bone scan with 2 or more new lesions (Prostate Cancer Working Group 3 \[PCWG3\])
- •Prior treatment with a second-generation AR-targeting agent (e.g. abiraterone acetate, enzalutamide, apalutamide) is required. Patients may have received up to two such agents
- •Patients may have received prior treatment with immunotherapies (sipuleucel-T, checkpoint immunotherapies) or bone targeting therapies (radium-223)
- •Both chemotherapy-naive and patients previously treated with chemotherapy are eligible. Chemotherapy pretreated patients may have received a maximum of two prior systemic cytotoxic chemotherapies completed at least 3 weeks prior to initiation of study treatment
Exclusion Criteria
- •Radiation therapy to primary tumor or metastatic sites within 2 weeks of cycle 1, day 1
- •Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to randomization
- •A malignancy (other than the one treated in this study) which required radiotherapy or systemic treatment within the past 1 year, or has a \>= 30% probability of recurrence within 24 months (except for non-melanoma skin cancer or Ta urothelial carcinomas)
- •Chronically uncontrolled hypertension, defined conventionally as consistent systolic pressures above 160 or diastolic pressures above 100 despite anti-hypertensive therapy. Note that this is NOT a criterion related to particular blood pressure (BP) results at the time of assessment for eligibility, nor does it apply to acute BP excursions that are related to iatrogenic causes, acute pain or other transient, reversible causes. (For example doctor's visit related stress i.e. "white coat syndrome")
- •Eye conditions likely to increase the risk of eye toxicity including
- •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
- •History 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)
Arms & Interventions
Treatment (erdafitinib, biospecimen collection)
Patients receive erdafitinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may also undergo collection of blood and bone marrow via biopsy and aspirates.
Intervention: Biopsy
Treatment (erdafitinib, biospecimen collection)
Patients receive erdafitinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may also undergo collection of blood and bone marrow via biopsy and aspirates.
Intervention: Biospecimen Collection
Treatment (erdafitinib, biospecimen collection)
Patients receive erdafitinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may also undergo collection of blood and bone marrow via biopsy and aspirates.
Intervention: Erdafitinib
Outcomes
Primary Outcomes
Bone specific alkaline phosphatase (BAP) modulation
Time Frame: Up to 5 years
Will assess modulation of BAP under the influence of treatment. Calculated as the maximal percentage change (decrease versus increase) on treatment. BAP in blood samples will be used for the primary analysis. Proportion of patients with BAP reduction along with the 95% confidence interval (95% CI) will be estimated.
Secondary Outcomes
- Prostate specific antigen modulation(Up to 5 years)
- Overall response rate(Up to 5 years)
- Progression-free survival(Duration in weeks/months from the time of treatment start to the date of disease progression or death, whichever is reported first, assessed up to 5 years)
- Time on treatment(Duration in weeks/months from the time of treatment start until the patient goes off treatment for any reason, assessed up to 5 years)
- Overall survival(Duration in weeks/months from the time of treatment start to the date of death, assessed up to 5 years)
- Incidence of adverse events(Up to 5 years)