Patients with muscle-invasive bladder cancer MedDRA version: 18.1 Level: PT Classification code 10005010 Term: Bladder cancer stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.1 Level: PT Classification code 10005011 Term: Bladder cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.1 Level: PT Classification code 10005012 Term: Bladder
Conditions
Interventions
Trade Name: JAVLOR®
Product Name: Javlor
Pharmaceutical Form: Concentrate for solution for infusion
Trade Name: Cisplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed
Sponsors
Ligartis GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged = 18 years and = 75 years with legal capacity 2. Signed written informed consent 3. Histologically confirmed muscle-invasive urothelial cell carcinoma of the bladder (MIBC) with clinical T2-T4a (N0/Nx, M0) assessed by primary PDD-guided TUR-B and by the screening magnetic resonance imaging (MRI) 4. Confirmed adequate complete resection of all visible tumor during TUR-B according to current treatment guidelines before registration; the latest TUR-B must have been done = 8 weeks before registration 5. ECOG performance status of 0 or 1 6. Adequate bone marrow, renal and hepatic functions as evidenced by the following: • Absolute Neutrophil Count = 2,000 mm3 and = 7,500 mm3 • Hemoglobin = 12 g/dL for the safety phase of the study; if the study treatment proved to be adequate tolerated during this safety phase, the threshold can be lowered to = 10 g/dL according to the decision of the study steering committee • Platelet count = 100,000 mm3 • Serum albumin within normal range • Serum total bilirubin = 1.5 x upper limit of normal (ULN) • Transaminases (ALT, AST) = 1.5 x ULN • Creatinine clearance = 60 mL/min, calculated based on a 24h-measured creatinine clearance • Serum Urea =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Prior systemic chemotherapy for any kind of malignancy; prior intravesical chemo¬therapy or treatment with BCG is allowed 2. Prior radiation of the pelvis or any prior radiation to >= 30% of the bone marrow 3. Evidence of lymph node (N+) or distant metastasis (M1) in the screening MRI assessment, iningcluding known brain metastases or leptomeneal involvement (however, brain-MRI-scans are not required to rule out CNS-involvement, unless there is clinical suspicion of central nervous system (CNS) disease) 4. Other malignancies except adequately treated basal carcinoma of the skin, localized prostate cancer Gleason = 6, in-situ cervix carcinoma or any other tumor with a disease free interval = 5 years 5. Peripheral neuropathy Grade = 2 NCI CTCAE v4.03 or hearing impairment Grade = 2 NCI CTCAE v.4.03 6. Any concurrent chronic system immune therapy or previous organ allograft 7. Weight loss >5% within the last 3 months before registration 8. Any other serious illness or medical condition including: • Infection requiring systemic anti-infective therapy within the last 2 weeks before registration • History of cardio-vascular disease that might compromise the safe administration of cisplatin • Dehydration requiring IV fluid substitution • Any medical condition that might not be controlled, e.g. patients with unstable angina pectoris, myocardial infarction NYHA grade I 9. Known hypersensitivity to the study drugs or to drugs with similar chemical structures 10. Treatment with any potent CYP3A4 inhibitor or inductor (e.g. ketoconazole, itraconazole, ritonavir, amprenavir, indinavir, rifampicine) or phenytoine; replacement of such treatment with alternative treatment options before start of study treatment is acceptable, if medically feasible and ethically acceptable 11. Treatment with hexamethylmelamin, pyridoxine, penicillamine or any other drug with known potential to affect the efficacy of cisplatin 12. Treatment with any other investigational or anti-cancer therapy = 30 days before registration 13. Pregnant or lactating female patients or female patients of childbearing potential with positive pregnancy test at screening 14. Women of child-bearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 6 months after the study 15. Sexually active fertile men not using effective birth control during the study and up to 6 months after the study if their partners are women of child-bearing potential
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Rate of pathological complete response (pCR) at cystectomy assessed by central pathological review (Prof. Hartmann, Erlangen), if the initial safety phase allows continuation of the trial with the phase II part;Secondary Objective: o Overall radiological response rate before cystectomy (RECIST v1.1) o Progression rate after 2 and 4 cycles of treatment (RECIST v1.1) o Safety of chemotherapy o Rate of complications at cystectomy o Perioperative morbidity/mortality (30 days and 90 days post surgery) o Cancer-specific survival o QoL (GIQLI, QLQ-C30, FACT, TNQ) ;Primary end point(s): The primary outcome measure will be the pathological tumor response based on central pathological review.;Timepoint(s) of evaluation of this end point: Evaluation at cystectomy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary and exploratory endpoints will be as follows: • Further efficacy measures determined using RECIST criteria (version 1.1): Tumor assessment at baseline, after Cycle 2, and prior to cystectomy; later assessments (1 month, 3 months, and 1 year) after cystectomy will be based on non-RECIST standardized assessments. • Safety measures: Physical examination and vital signs, performance status, complete blood count, serum biochemistry and electrolytes, (serious) adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI/CTCAE v4.03). Documentation of any prophylactic and therapeutic measures, length of stay in case of hospitalization (cystectomy), readmission to hospital (cystectomy). • Identification and evaluation of markers to predict response of neo-adjuvant chemotherapy with VFL plus CDDP prior to cystectomy. ;Timepoint(s) of evaluation of this end point: Timepoints are: Baseline After Cylce 2 Prior to cystectomy 1, 3 and 12 month past cystectomy | — |
Countries
Germany
Contacts
Public ContactHeidrun Rexer
MeckEvidence
Outcome results
None listed