An Efficacy and Safety Study of Erdafitinib (JNJ-42756493) in Participants With Urothelial Cancer
Condition: Urothelial Cancer
Intervention: Erdafitinib; Midazolam; Metformin
Intervention description: 8 mg orally once daily for 28 days on a 28 day cycle.; Participants who enrolled in DDI substudy will receive pretreatment with single dose of midazolam on Day -2 and single dose of midazolam on Day 13.; Participants who enrolled in DDI substudy will receive pretreatment with single dose of metformin on Day -1 and single dose of metformin on Day 14.
Intervention MeSH terms: Metformin; Midazolam
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 239.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Urothelial Cancer; JNJ-42756493; Erdafitinib; Tyrosine Kinase Inhibitor

Summary:

      The purpose of this study is to evaluate the objective response rate (complete response [CR]+
      partial response [PR]) of the selected dose regimen in participants with metastatic or
      surgically unresectable urothelial cancers that harbor specific FGFR genomic alterations.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must have histologic demonstration of metastatic or surgically unresectable urothelial
             cancer. Minor components of variant histology such as glandular or squamous
             differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or
             micropapillary change are acceptable

          -  Must have measurable disease according to the Response Evaluation Criteria in Solid
             Tumors (RECIST, version 1.1) at baseline

          -  Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0, 1,
             or 2

          -  Must have adequate bone marrow, liver, and renal function as described in protocol

          -  Negative pregnancy test (urine or serum beta human chorionic gonadotropin [b-hCG]) at
             Screening for women of child bearing potential who are sexually active

          -  Must have shown disease progression according to RECIST, version 1.1, following prior
             chemotherapy for metastatic or surgically unresectable urothelial cancer. Participants
             who received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or
             progression according to RECIST, version 1.1, within 12 months of the last dose are
             considered to have received chemotherapy in the metastatic setting. These participants
             will be referred to as chemo-refractory participants. (Participants who have shown
             disease progression according to RECIST, version 1.1 following prior treatment with
             anti-Programmed death-ligand 1 (anti PDL1/PD1) antibodies are also eligible) For DDI
             substudy

          -  Disease progression following prior chemotherapy for metastatic or surgically
             unresectable urothelial cancer. Participants who received neoadjuvant or adjuvant
             chemotherapy and showed disease recurrence or progression within 12 months of the last
             dose are considered to have received chemotherapy in the metastatic setting

        Exclusion Criteria:

          -  Received chemotherapy, targeted therapies, definitive radiotherapy, or treatment with
             an investigational anticancer agent within 2 weeks (in the case of nitrosoureas and
             mitomycin C, within 6 weeks; in the case of immunotherapy, within 4 weeks) before the
             first administration of study drug. Localized palliative radiation therapy (but should
             not include radiation to target lesions) and ongoing bisphosphonates and denosumab,
             are permitted

          -  Has persistent phosphate level greater than upper limit of normal (ULN) during
             screening (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

          -  Females who are pregnant, breast-feeding, or planning to become pregnant within 3
             months after the last dose of study drug and males ho plan to father a child while
             enrolled in this study or within 5 months after the last dose of study drug

          -  Has not recovered from reversible toxicity of prior anticancer therapy (except
             toxicities which are not clinically significant such as alopecia, skin discoloration,
             or Grade 1 neuropathy)