Carboplatin and Gemcitabine Hydrochloride With or Without Vandetanib as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Urinary Tract Cancer

Bladder Cancer Clinical Trial

Official title:

A Randomized Phase II Trial of Carboplatin and Gemcitabine +/- Vandetanib in First Line Treatment of Advanced Urothelial Cell Cancer in Patients Who Are Not Suitable to Receive Cisplatin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01191892
• Other study ID #: CDR0000684016
• Secondary ID: WCTU-TOUCANISRCT
• Status: Completed
• Phase: Phase 2
• Start date: June 2010
• Est. completion date: September 5, 2016

Study information

• Verified date: May 2019
• Source: Cardiff University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as carboplatin and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether giving carboplatin and gemcitabine hydrochloride is more effective with or without vandetanib as first-line therapy in treating urinary tract cancer.

PURPOSE: This randomized phase II trial is studying giving carboplatin together with gemcitabine hydrochloride and to see how well it works when given with or without vandetanib as first-line therapy in treating patients with locally advanced or metastatic urinary tract cancer.

Description:

OBJECTIVES:

Primary

• To determine the antitumor activity (as measured by progression-free survival) of carboplatin and gemcitabine hydrochloride with versus without vandetanib as first-line treatment in patients with locally advanced or metastatic urothelial cell cancer who are not suitable to receive cisplatin.

Secondary

• To determine the safety, feasibility, and tolerability of these regimens in these patients.

• To determine the objective response rate.

• To determine the overall survival of patients treated with these regimens

• To assess the change of size of measurable lesions at 9 weeks of study therapy.

OUTLINE: This is a multicenter study. Patients are stratified according to relevant factors. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive carboplatin IV over 30 minutes on day 1, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and an oral placebo once daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Patient receive carboplatin and gemcitabine hydrochloride as in arm I. Patients also receive oral vandetanib once daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Blood and urine samples may be collected for laboratory analysis at baseline and after completion of study.

After completion of study treatment, patients are followed up at weeks 18, 26, 39, and 52.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: September 5, 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell carcinoma (pure or mixed histology) of the urothelium (upper or lower urinary tract)

• Cancers with other pathologies are permitted provided the dominant morphology is transitional cell carcinoma

• Radiologically measurable disease according to RECIST v 1.1 criteria

• Locally advanced and/or metastatic disease not amenable to curative treatment with surgery or radiotherapy

• Patient not suitable for cisplatin therapy, meeting 1 or more of the following criteria:

• More than 75 years of age

• ECOG performance status > 2

• Creatinine clearance < 30 mL/min

• Clinically significant ischemic heart disease (myocardial infarction or unstable angina more than 3 but less than 12 months prior to date of randomization, symptomatic angina, or NYHA class I within 3 months prior to date of randomization)

• Prior intolerance of cisplatin

• Any other factor that, in the opinion of the investigator, indicates that cisplatin is not suitable for the patient (e.g., unilateral hearing loss)

PATIENT CHARACTERISTICS:

• See Disease Characteristics

• ECOG performance status 0-2

• Serum bilirubin = 1.5 times upper limit of normal (ULN)

• Creatinine clearance = 30 mL/min

• Potassium = 4.0 mmol/L OR below the CTCAE grade 1 upper limit

• Magnesium normal OR below the CTCAE grade 1 upper limit

• Serum calcium = 2.9 mmol/L (If serum calcium is < lower limit of normal [LLN], then adjusted serum calcium must be = LLN)

• ALT/AST = 2.5 times ULN

• Alkaline phosphatase = 2.5 times ULN (< 5 times ULN if judged by the investigator to be related to liver metastases)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier-method contraception during and for 3 months (women) or 2 months (men) after completion of study therapy

• No evidence of severe or uncontrolled systemic disease or any concurrent condition that, in the investigator's opinion, makes it undesirable for the patient to participate in the trial or that would jeopardize compliance with the protocol

• No significant risk of cardiac complications, defined as any of the following:

• Clinically significant cardiovascular event (e.g., myocardial infarction, superior vena cava syndrome [SVC], NYHA classification of heart disease = class II within 3 months prior to entry, or presence of cardiac disease that, in the opinion of the investigator, significantly increases the risk of ventricular arrhythmia)

• History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia

• Atrial fibrillation, controlled on medication, is not exclusionary

• No QTc prolongation with other medications that requires discontinuation of that medication

• No congenital long QT syndrome or first-degree relative with unexplained sudden death under 40 years of age

• No QTc that is immeasurable or = 480 msec on screening ECG

• If a patient has a QTc interval = 480 msec on screening ECG, the ECG screen may be repeated twice (at least 24 hours apart) and the average QTc from the three screening ECGs must be < 480 msec in order for the patient 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

• No presence of left bundle branch block

• No hypertension not controlled by medical therapy (systolic blood pressure > 160 mm Hg or diastolic blood pressure > 100 mm Hg)

• No currently active diarrhea that, in the investigator's opinion, may affect the ability of the patient to either absorb vandetanib or to tolerate additional diarrhea episodes

• No previous or current malignancies of other histology within the past 5 years except for carcinoma in situ of the cervix, adequately treated basal cell or squamous cell carcinoma of the skin, or prostate cancer

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 2 weeks since prior and no concurrent known potent CYP3A4 inducers (e.g., barbiturates, rifampicin, rifabutin, phenytoin, carbamazepine, troglitazone, phenobarbital, or St. John wort) or medication that has known adverse interactions with vandetanib

• Dexamethasone (or equivalent) allowed as a pre-medication for chemotherapy

• At least 4 weeks since prior major surgery and complete surgical wound healing

• At least 30 days since prior and no other concurrent investigational agents

• No prior chemotherapy (unless delivered perioperatively and completed > 12 months prior to first presentation of recurrent disease)

• No other concurrent anticancer drug

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma, Transitional Cell
• Kidney Neoplasms
• Transitional Cell Cancer of the Renal Pelvis and Ureter
• Ureter Cancer
• Ureteral Neoplasms
• Urethral Cancer
• Urethral Neoplasms
• Urinary Bladder Neoplasms

Intervention

Drug:
• carboplatin

• gemcitabine hydrochloride

• vandetanib

• Placebo
Placebo of vandetanib tablet

Locations

Country	Name	City	State
United Kingdom	Ayr Hospital	Ayr
United Kingdom	Royal Bournemouth General Hospital	Bournemouth
United Kingdom	Queens Hospital	Burton upon Trent
United Kingdom	Wales Cancer Trials Unit	Cardiff	Wales
United Kingdom	Velindre Hospital	City And County Of Cardiff
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Calderdale Royal Infirmary	Halifax
United Kingdom	Huddersfield Royal Infirmary	Huddersfield
United Kingdom	The Royal Lancaster Infirmary	Lancaster
United Kingdom	St. James's University Hospital	Leeds
United Kingdom	Charing Cross Hospital	London
United Kingdom	St Marys Hospital	London
United Kingdom	The Royal Free Hospital	London
United Kingdom	Christie Hospital	Manchester
United Kingdom	Mount Vernon Hospital	Northwood Middlesex
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Weston Park Hospital	Sheffield
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	Royal Surrey County Hospital	Surrey
United Kingdom	The Royal Marsden Hospital	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
Cardiff University

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival	Time to event PFS, follow-up to 1 year	1 year
Secondary	Tolerability and feasibility	Rate of randomisation and safety profile of randomised patients	1 year
Secondary	Objective response rate as assessed by RECIST criteria	Proportion of patients responding to treatment	Up to 1 year
Secondary	Overall survival	Patients will be followed up until death by using NHS flagging service.	2 years
Secondary	Change in size of measurable lesions 9 weeks after start of chemotherapy		9 weeks
Secondary	Toxicity during and after treatment as assessed by NCI CTCAE v 4.0		1 year