ERDAFITINIB for Urothelial cancer

Inclusion criteria

• {"criterion_text":"- 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"}
• {"criterion_text":"- Must have measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline"}
• {"criterion_text":"- Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0, 1, or 2"}
• {"criterion_text":"- Must have adequate bone marrow, liver, and renal function as described in protocol"}
• {"criterion_text":"- Negative pregnancy test (urine or serum beta human chorionic gonadotropin [bhCG]) at Screening for women of child bearing potential who are sexually active"}
• {"criterion_text":"- Must have shown disease progression according to RECIST, version 1.1, following prior chemotherapy for metastatic or surgically unresectable urothelial cancer. Subjects 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 subjects will be referred to as chemorefractory subjects. (Subjects who have shown disease progression according to RECIST, version 1.1 following prior treatment with antiProgrammed deathligand 1 (anti PDL1/PD1) antibodies are also eligible)"}
• {"criterion_text":"- Subjects with target FGFR mutations or FGFR gene fusions are eligible for enrollment in the substudy, as determined by local screening."}
• {"criterion_text":"- Subject (or his/her legally acceptable representative) must sign the informed consent documents indicating that they understand the purpose of procedures required for the DDI substudy and continuation of treatment until disease progression and are willing to participate in the study."}

Exclusion criteria

• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Has a history of or current uncontrolled cardiovascular disease"}
• {"criterion_text":"- Females who are pregnant, breastfeeding, or planning to become pregnant within 3 months after the last dose of study drug and males who plan to father a child while enrolled in this study or within 5 months after the last dose of study drug."}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade."}
• {"criterion_text":"- Medications known to induce or inhibit CYP3A or CYP2C9, or inhibit OCT2 must be discontinued or substituted 1 week prior to the first intake of the probe drugs, or must be temporarily interrupted during the course of the DDI substudy"}
• {"criterion_text":"- Use of midazolam and metformin from 2 weeks before the first intake of probe drugs (for DDI purpose on Day -2 or Day -1), and until the last PK sample is collected on Study Day 15 (last 24-hour PK sampling)."}
• {"criterion_text":"- Known contraindication to the use of metformin and/or midazolam, based on the local prescribing information."}

Primary endpoints

• {"endpoint_text":"- Percentage of Participants with Best Overall Response","definition_or_measurement_approach":"Best Overall Response measured per RECIST v1.1; main objective specifies objective response rate (complete response [CR] + partial response [PR]) of the selected dose regimen."}
• {"endpoint_text":"- The endpoints are PK parameters for midazolam and its metabolite (1-OH-midazolam), and for metformin (in the absence or presence of erdafitinib) including but not limited to Cmax, tmax, AUClast, and AUC∞.","definition_or_measurement_approach":"Pharmacokinetic parameters (Cmax, tmax, AUClast, AUC∞ and others) of midazolam, 1-OH-midazolam, and metformin measured with and without repeated dosing of erdafitinib to assess DDI effects."}

Spain

Earliest CTIS Part Ii Submission Date

13-12-2023

Latest Decision Or Authorization Date

17-03-2025

Processing Time Days

460

Number Of Sites

4

Number Of Participants

4

France

Earliest CTIS Part Ii Submission Date

13-12-2023

Latest Decision Or Authorization Date

06-02-2025

Processing Time Days

421

Number Of Sites

1

Number Of Participants

1

Primary sponsor

Full Name

Janssen Cilag International

Organisation Type

Pharmaceutical company

Country Of Registered Address

Belgium

Contract research organisations

Name

Perceptive Eclinical Limited

Responsibilities

sponsorDuties code 3; contact Martin.Preis@calyx.ai

Third parties

• {"country":"United Kingdom","full_name":"Perceptive Eclinical Limited","duties_or_roles":"sponsorDuties code 3","organisation_type":"Pharmaceutical company"}