EOadjuvant chemotherapy study of Nintedanib with Gemcitabine and Cisplatin in locally advanced muscle invasive BLADder cancEr

Phase 2

Completed

• Conditions: Topic: Cancer; Subtopic: Bladder Cancer; Disease: Bladder (advanced); Cancer

• Registration Number: ISRCTN56349930
• Lead Sponsor: Clatterbridge Centre for Oncology NHS Trust (UK)

Brief Summary

2020 Abstract results in https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.6_suppl.438 results presented at ASCO (added 17/08/2020) 2022 Results article in https://pubmed.ncbi.nlm.nih.gov/35421369/ (added 19/04/2022)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-04-23
• Study Completion: 2016-11-30
• Last Update Posted: 2 May 2022

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 120

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 <1.5 xULN
6.2. Alkaline Phosphatase (ALP) levels <2 xULN
6.3. Aspartate transaminase (AST)/Alanine transaminase (ALT) levels <3.0 xULN
7. Glomerular Filtration Rate (GFR) > 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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> 1. Pathological complete response;<br> Timepoint(s): ? Baseline (standard diagnostic biopsy)<br> ? End of cycle 3 of neoadjuvant treatment<br> ? Following neoa<br>

Secondary Outcome Measures

Name	Time	Method
<br> 1. Primary outcome (Safety Sub-study): MTD of Nintedanib to be confirmed for renally impaired patients; Timepoint(s): 6 months<br> 2. Secondary outcomes (Phase II Main study):<br> 2.1. Overall Survival; Timepoint(s): 5 years<br> 2.2. Progression free survival; Timepoint(s): 5 years<br> 2.3. Toxicity; Timepoint(s): 5 years<br>