Topic: Cancer
Conditions
Interventions
Nintedanib, Triple Kinase Inhibitor
Nintedanib/Placebo, Triple Kinase Inhibitor or Inactive Placebo
The visit schedule and assessments for the safety sub-study and the main study are the same. Initially patients will go for a screening
Sponsors
Clatterbridge Centre for Oncology NHS Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 18 or over 2. Histologically proven invasive TCC of bladder 3. Localised muscle invasive carcinoma either surgically or by imaging (T2-T4a N0 M0 ) 4. ECOG performance status grade 0 to 1 5. Adequate haematological function as evidenced by: 5.1. Haemoglobin >10.0g/dl 5.2. White blood cell count >3.0 x10 9/L 5.3. Absolute neutrophil count >1.5 x10 9/L 5.4. Platelet count >100,000/mm3 6. Adequate Hepatic function as evidenced by: 6.1. Total Bilirubin 60ml/min* measured by either: 7.1. EDTA clearance 7.2. 24 hr Urine collection 7.3. The Cockcroft-Gault calculation As per local standard practice; Available for 12month follow up 8. Agree to use adequate contraception which they agree to continue for 3 months after the study treatment 9. Suitable for treatment with Gemcitabine and Cisplatin 10. Able to receive radical treatment 11. Able to provide written informed consent *Following safety review from the safety substudy, the ISDMC and the funder will decide whether the data indicates that it is suitable for patients with impaired GFR (40-60 ml/minute) to be included in the trial using split dose cisplatin 35 mg/m2 on day 1 and day 8 and which dose of Nintedanib/Placebo will be used for the main study.
Exclusion criteria
Exclusion criteria: 1. Pregnant or breast feeding 2. Concomitant or previous malignancy which is likely to interfere with protocol treatment 3. Evidence of significant clinical disorder, or laboratory finding which, in the opinion of the investigator, makes it undesirable for the patient to participate in the trial. 4. Male and female patients (of childbearing potential* not using adequate contraception and do not agree to do so for 3 months following Nintedanib treatment 5. Evidence of metastatic disease * Patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation/salpingectomy, or postmenopausal for at least two years. Note: Patients with hydronephrosis can be included if the kidney/ureter has been stented, or nephrostomy has been inserted, and renal function has been maintained to allow neoadjuvant chemotherapy to be administered satisfactorily
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Pathological complete response; Timepoint(s): ? Baseline (standard diagnostic biopsy) ? End of cycle 3 of neoadjuvant treatment ? Following neoa | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Primary outcome (Safety Sub-study): MTD of Nintedanib to be confirmed for renally impaired patients; Timepoint(s): 6 months 2. Secondary outcomes (Phase II Main study): 2.1. Overall Survival; Timepoint(s): 5 years 2.2. Progression free survival; Timepoint(s): 5 years 2.3. Toxicity; Timepoint(s): 5 years | — |
Countries
England, United Kingdom
Outcome results
None listed