Study evaluating safety and efficacy of Pemigatinib drug as post-operative therapy for selected, high-risk patients with urothelial carcinoma who have received radical surgery. A European Association of Urology Research Foundation clinical trial
- Conditions
- pT3-4 and/or pN1-3 urothelial carcinoma (UC) of the urinary bladder or upper urinary tract after radical cystectomy /radical nephroureterectomy previously treated with at least three cycles of neoadjuvant cisplatin-based chemotherapy or, if neoadjuvant chemotherapy was not administered, ineligible to receive cisplatin-based adjuvant chemotherapy, with evidence of FGFR3 alterationsMedDRA version: 20.0Level: LLTClassification code 10046714Term: Urothelial carcinoma bladderSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001833-14-FR
- Lead Sponsor
- EAU Research Foundation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 56
1. Men and woman, aged 18 years or older with histological evidence of pT3-4 and/or pN1-3 urothelial cancer (UC) of the urinary bladder or upper urinary tract after radical cystectomy/radical nephroureterectomy. Patients with mixed histologies are required to have a dominant (i.e. at least 50%) urothelial cell carcinoma pattern
2. Previous administration of at least 3 cycles of neoadjuvant cisplatin-based chemotherapy OR, if neoadjuvant chemotherapy was not administered, ineligibility to receive cisplatin-based adjuvant chemotherapy based on Galsky’s criteria, that include at least one of the following: (1) WHO performance status = 2 and/or (2) creatinine-clearance < 60 ml/min and/or (3) CTCAE Gr= 2 hearing loss and/or (4) CTCAE Gr = 2 neuropathy
3. Evidence of FGFR3 alterations (mutations or gene fusions as specified in protocol) as assessed by a centralized Foundation Medicine test (Foundation One CDx assay). A list of the allowed FGFR alterations is provided the study protocol
4. Recovered with no evidence of disease confirmed by radiological images, prior to start of adjuvant therapy within 13 weeks after radical surgery
5. WHO performance status of 0, 1 or 2
6. Willingness to avoid pregnancy or fathering children. If the patient is male, he must use a condom during sexual intercourse during the treatment period and 240 days thereafter (120 days to eliminate study treatment and 120 days spermatogenesis cycle) plus partner use of a contraceptive method with a failure rate of <1% per year (See Appendix 1 of the protocol). If the patient is female, and of childbearing potential, she must practice adequate contraception (Appendix 1 of the study protocol)
for 30 days prior to administration of study treatment, have a negative pregnancy test and continue such precautions during the study treatment period and for 150 days after the last study treatment (120 days to eliminate study treatment and 30 days menstruation cycle) (See Appendix 1 of the study protocol for standards of adequate contraceptive methods)
7. Written informed consent for screening of tumor tissue and if evidence of FGFR alterations written informed consent for the start of the complete study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 38
1. Any previous receipt of a selective FGFR inhibitor
2. Presence of primary CIS only
3. Presence of another malignancy in the 3 years before enrolment except for basal cell carcinoma or squamous cell carcinoma of the skin, cis of cervix, localised prostate cancer in active surveillance or other non invasive or other indolent malignancy that has undergone potentially curative therapy
4. Presence of pregnancy or lactation or not willing to avoid pregnancy or fathering children
5. Distant metastases (M1 disease) or presence of radiological evidence of disease at baseline
6. Treatment with other investigational drugs, receipt of anticancer medications or radiotherapy of the bladder or upper urinary tract prior to- or after radical surgery
7. Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half lives (whichever is longer) before the first dose of study Tx
8. Abnormal laboratory parameters:
- Total bilirubin = 1.5 × upper limit of normal (ULN; = 2.5 × ULN if Gilbert syndrome);
- AST and/or ALT > 2.5 × ULN;
- Creatinine clearance = 30 mL/min based on Cockroft-Gault;
- Serum phosphate > institutional ULN;
- Serum calcium outside of the institutional normal range or serum albumin-corrected calcium outside of the institutional normal range when serum albumin is outside of the institutional normal range
9. History of human immunodeficiency virus infection or active tuberculosis infection
10. Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (exceeding >10 mg daily of prednison equivalent; inhalation steroids are permitted)
11. Evidence of hepatitis B virus or hepatitis C virus active infection or risk of reactivation
12. History of clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from enrollment, NYHA Class III or IV (Appendix 4 of the Protocol)
13. Current evidence of corneal disorder/keratopathy (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, etc) or retinal disorder (including but not limited to, central serous retinopathy, macular/retinal degeneration, diabetic retino-pathy, retinal detachment, etc) as confirmed by ophthalmologic examination
14. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending the required study visits
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