A Phase 2, open-label, multi-centre, multi-national interventional trial to evaluate the efficacy and safety of erdafitinib (ERDA) monotherapy and erdafitinib (ERDA) and cetrelimab (CET) combination as neoadjuvant treatment in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC) whose tumours express FGFR gene alterations (SOGUG-NEOWIN)
- Conditions
- Muscle-invasive bladder cancer (MIBC)MedDRA version: 20.0Level: PTClassification code: 10005003Term: Bladder cancer Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2024-512573-27-01
- Lead Sponsor
- Grupo Espanol De Oncologia Genitourinaria-Socug
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 67
1.Written informed consent stating that he or she understands the purpose of the study and the procedures involved and agrees to participate in the study., 10. Willingness to avoid pregnancy or fathering children based on the criteria below: a. Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last dose of erdafitinib and/or 150 days after the last dose of cetrelimab, unless confirmed to be azoospermic (vasectomized or secondary to medical cause). b. Women of childbearing potential must have a negative serum pregnancy test at screening and before the first dose on Day 1 and must agree to take appropriateprecautions to avoid pregnancy (with at least 99% certainty) from screening through 90 days after the last dose of erdafitinib and/or 150 days after the last dose of cetrelimab (Acceptable contraception is defined in Appendix 8). A WOCBP is a female who 1) has achieved menarche at some point 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 12 consecutive months (has had at least menses at any time preceding 12 consecutive months). Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR = 12 months of aamenorrhea) are eligible., 2. Histologically confirmed diagnosis of MIBC (Stage T2-4a N0/N1 M0) obtained via a diagnostic or maximal TURBT performed no later than 3 months prior to start the screening visit., 3. Pure or predominant (=50%) UC histology as determined at the local site., 4. Age = 18 years., 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1., 6. Decline or ineligible (unfit”) for cisplatin-based chemotherapy as defined by any one of the following criteria: a. Impaired renal function (glomerular filtration rate [GFR] = 30 but < 60 mL/min). GFR should be assessed by direct measurement (ie, creatinine clearance) or, if not available, by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. b. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 = Grade 2 hearing loss (assessed per local standard of care). c. CTCAE, Version 5.0 = Grade 2 peripheral neuropathy. d. Any other reason to be ineligible for cisplatin should be consulted with the coordinating PI., 7. Presence of a selected FGFR alteration on analysis of tumour biopsy. Local reports based on validated tests can be accepted (with subsequent confirmation by Central Laboratory). Patients having positive local testing will not have to wait for confirmation to be enrolled. It is required fromall patients to send tumour sample to Central Laboratory to analyse DNA mutations and RNA fusion by Next Generation Sequencing and eCounter, respectively. In case of discrepancies, the local determination will prevail., 8. Have adequate organ function confirmed by the following laboratory values obtained within 14 days prior to Cycle 1 Day 1 (medical management allowed): a. Absolute Neutrophil Count (ANC) =1.5 x 109/L. b. Platelets =100 x 109/L. c. Haemoglobin =9 g/dL (5.6 mmol/L). d. International normalized ratio (INR) or Prothrombin time (PT) =1.5 x ULN e. Total bilirubin =1.5 x ULN except patients with Gilbert Syndrome, who must have a total bilirubin level of <3.0 x ULN. f. ALT and AST =2.5 x
1. Clinical evidence of N2-N3 tumours or metastatic bladder cancer., 10. Uncontrolled adrenal insufficiency., 11. True positive test results for hepatitis B, or C during screening., 12. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)., 13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia requiring medication except for atrial fibrillation that is rate controlled with medication, myocardial infarction within 6 months of Cycle 1 Day 1, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent., 14. Known allergy or hypersensitivity to study drug formulations., 15. Known history of allergy to protein-based therapies or a history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or immune-mediated thrombocytopenia or anemia)., 16. Current central serous retinopathy (CSR) or retinal pigment epithelial detachment (RPED) of any grade., 17. Inability to swallow and retain oral medication., 18. History of calcium and phosphate homeostasis disorder or systemic mineral imbalance., 19. Inability or unlikeliness of the participant to comply with the dose schedule and study evaluations, in the opinion of the investigator., 2. Has tumour with any neuroendocrine or small cell component., 20. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drug., 21. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed., 22. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis., 23. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. A screening QTcF interval > 480 ms is excluded., 3. Patients who are not considered fit for cystectomy or reject cystectomy., 4. Patients with co-morbidities that will preclude them from trial intervention., 5. Prior FGFR-targeted or antiPD1/PDL1 systemic therapy., 6. Prior systemic therapy, radiation therapy, or surgery for bladder cancer other than transurethral resection of bladder tumour (TURBT) or biopsies is not permitted. Prior BCG or other intravesical treatment of non-MIBC is permitted if completed at least 6 weeks prior to initiating study treatment., 7. Evidence of UC in upper urinary tracts (ureters or renal pelvis), prostatic urethra,history of previous MIBC or UC not confined to the bladder., 8. Major surgical procedure within 14 days prior to the first dose or still recovering from prior surgery., 9. Severe infection within 4 weeks prior to allocation.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method