A trial of carboplatin and gemcitabine +/- vandetanib to treat patients with advanced bladder cancer who can't be treated with cisplati
- Conditions
- Transitional cell carcinoma of urothelium (upper or lower urinary tract). Cancers with other pathologies are permitted, provided that the dominant morphology is transitional cell carcinoma.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2009-010140-33-GB
- Lead Sponsor
- Cardiff University
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 82
Patients meeting all of the following criteria may be included in the trial:
1.Male or female
2.Age greater than or equal to 18 years
3.Histologically confirmed transitional cell carcinoma (pure or mixed histology) of urothelium (upper or lower urinary tract). Cancers with other pathologies are permitted, provided that the dominant morphology is transitional cell carcinoma.
4.Radiologically measurable (RECIST 1.1), locally advanced/and/or metastatic disease not amenable to curative treatment with surgery or radiotherapy not suitable for cisplatin, defined as one or more of the following:
a)Creatinine clearance <60ml/min estimated by Cockcroft and Gault formula or measured by 24-hour urine collection or isotope clearance (N.B. patients are excluded if creatinine clearance is <30ml/min)
b)ECOG Performance Status 2 (note patients are excluded if PS is 3 or worse)
c)Clinically significant ischemic heart disease (MI or unstable angina 3-12 months prior to date of randomisation, or symptomatic angina, New York Heart Association Class I, 0-3 months prior to date of randomisation). See section 4 of exclusion criteria.
d)Prior intolerance of cisplatin
e)Age greater than 75
f)Any other factor, which, in the opinion of the investigator indicates that cisplatin is not suitable for this patient (e.g. unilateral hearing loss)
5.The patient has provided written informed consent.
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 82
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 82
If any of the following criteria apply, patients cannot be included in the trial:
1.Laboratory results rendering patient unsuitable for trial treatment:
a)Serum bilirubin >1.5x the upper limit of reference range (ULRR)
b)Creatinine clearance < 30 mL/minute (calculated by Cockcroft-Gault formula or measured by 24-hour urine collection or isotope clearance).
c)Potassium, <4.0 mmol/L despite supplementation; or above the CTCAE grade 1 upper limit
d)Magnesium below the normal range despite supplementation, or above the CTCAE grade 1 upper limit
e)Serum calcium above the CTCAE grade 1 upper limit. In cases where the serum calcium is below the normal range, the calcium adjusted for albumin is to be obtained and substituted for the measured serum value. Exclusion is to then be based on the adjusted for albumin values falling below the normal limit.
f)Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x ULRR or alkaline phosphatase (ALP) >2.5 x ULRR, or > 5x ULRR if judged by the investigator to be related to liver metastases
2.Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
3.ECOG performance status = 3.
4.Significant risk of cardiac complications defined as any of the following:
a)Clinically significant cardiovascular event (e.g. myocardial infarction, superior vena cava syndrome (SVC), New York Heart Association (NYHA) classification of heart disease >2 within 3 months before entry; or presence of cardiac disease that, in the opinion of the investigator, significantly increases the risk of ventricular arrhythmia (N.B. this is complementary to inclusion criterion 4 (above)).
b)History of arrhythmia (multifocal premature ventricular contractions PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not exclusionary
5.QTc prolongation with other medications that required discontinuation of that medication
6.Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age
7.Presence of left bundle branch block (LBBB)
8.QTc that is unmeasurable or > 480 msec on screening ECG. (Note: If a subject has a QTc interval >480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be <480 msec in order for the subject to be eligible for the study.) Patients who are receiving a drug that has a risk of Torsades de Pointes are excluded if QTc is = 460 msec. Note: the method for estimating QTc must be consistent between all time points for any individual patient.
9.Concomitant medication which has known adverse interaction with vandetanib, including:
a)Any medication that may induce Torsades de Pointes (TdP). Note some medications that induce TdP may be continued with additional ECG monitoring
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The main objective of this trial is to assess whether the addition of vandetanib to standard carboplatin/gemcitabine cancer chemotherapy improves the clinical outcome for participants with advanced cancer of the urinary system (urothelial cancer).;Secondary Objective: The secondary objective of this trial is to determine if the 3-drug chemotherapy combination of vandetanib, carboplatin and gemcitabine is safe and tolerable in participants with advanced cancer of the urinary system (urothelial cancer).;Primary end point(s): Progression-Free Survival (PFS). Progression is defined according to RECIST 1.1.;Timepoint(s) of evaluation of this end point: Six months after the last patient has been recruited into the study.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Tolerability (side effects) and feasibility of use (number of participants requiring dose delays or reductions and/or treatment withdrawal). Objective response rate as assessed by RECISTv1.1. Overall survival (OS). Time from enrolment to death. Those still alive will be censored at time last seen. Change of sum of measurable lesions 9 weeks after start of chemotherapy (using Waterfall plots) (measurements according to RECIST v1.1). Toxicity, during and after treatment using NCI CTCAE v4.0. SAEs will be collected in real time.;Timepoint(s) of evaluation of this end point: Six months after the last patient has been recruited into the study.