Low-grade Upper Tract Urothelial Carcinoma
Conditions
Brief summary
The primary purpose of this trial is to evaluate the safety & tolerability of Nadofaragene Firadenovec in subjects with LG-UTUC. To help with this evaluation, a safety lead-in period will be conducted for the first 6 subjects. Complete response is at 3 or 6 months defined as absence of any UTUC in the renal pelvis.
Interventions
Repeat dose trial to investigate the safety and efficacy of nadofaragene firadenovec instilled into the renal pelvis
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged ≥18 years at the time of signing informed consent. 2. Able to give written informed consent. 3. Have biopsy-proven low-grade upper tract urothelial cancer (LG-UTUC) confirmed by a pathology report ≤2 months prior to enrolment. 4. Have ≥1 measurable papillary low-grade tumour (5-15 mm in maximum diameter), evaluated visually above the ureteropelvic junction before enrolment. * Subjects with low-grade tumour larger than 15 mm will be eligible if endoscopic downsizing of the tumour to 5-15 mm in maximum diameter has been performed before enrolment. 5. Willing to be available for at least 18 months after first dosing. 6. Have life expectancy \>2 years, in the opinion of the investigator. 7. Have an Eastern Cooperative Oncology Group (ECOG) status of 2 or less. 8. Females of reproductive potential must have a negative highly sensitive urine or serum pregnancy test upon entry into this trial and be willing to use highly effective contraception during treatment with the investigational medicinal product (IMP) and for 6 months following the last dose. Otherwise, female subjects must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile. Highly effective methods of contraception include: combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, and sexual abstinence. 9. Male subjects with female partners of reproductive potential must be surgically sterile or willing to use a condom in addition to effective contraception in their female partner during treatment with the IMP and for 3 months following the last dose. 10. Adequate laboratory values: * haemoglobin ≥10 g/dL * white blood cells (WBC) ≥4000/μL * absolute neutrophil count (ANC) ≥2000/μL * platelet count ≥100,000/μL * international normalized ratio (INR)\* below institutional upper limit of normal (ULN) * activated partial thromboplastin time (aPTT)\* below institutional ULN * aspartate aminotransferase (AST) ≤1.5 x ULN * alanine aminotransferase (ALT) ≤1.5 x ULN * total bilirubin ≤1.5 x ULN * sodium \>135 mmol/L * potassium between 3.6 and 5.0 mmol/L 11. Have an estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2 (for inclusion in the safety lead-in the eGFR must be ≥60 mL/min/1.73 m2 \[see
Exclusion criteria
#20\]).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The number of treatment-emergent adverse events reported by each subject during the trial. | Up to 30 months | — |
| Complete response | Up to 6 months | defined as absence of any UTUC in the renal pelvis, i.e. negative urine cytology for high-grade urothelial carcinoma (centrally assessed), and either no suspicious lesions on ureteroscopy (investigator assessed) or a negative for-cause biopsy (centrally assessed). |
Secondary
| Measure | Time frame |
|---|---|
| Occurrence of anti-adenoviral antibodies. | Up to 30 months |
| Occurrence of anti-interferon-α2b (IFN-α2b) antibodies. | Up to 30 months |
| Shedding of adenoviral vector with IFN-α2b. | Before dose and up to 15 days after dose |
| Systemic exposures to IFN-α2b protein. | Before dose and up to 15 days after dose |
| Systemic exposures to adenoviral vector with IFN-α2b. | Before dose and up to 15 days after dose |
| Systemic exposures to Syn3NODA. | Before dose and up to 15 days after dose |
| Duration of response, defined as the time from first achieved complete response to disease recurrence, disease progression (defined as any high-grade disease) or disease-specific death, whichever occurs first. | Up to 30 months |
| Urinary excretion of IFN-α2b protein. | Before dose and up to 15 days after dose |
Countries
France, United States
Contacts
CONTACTFerring Pharmaceuticals
STUDY_DIRECTORGlobal Clinical Compliance
Ferring Pharmaceuticals
Outcome results
None listed