Carboplatin and Gemcitabine Hydrochloride With or Without Vandetanib as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Urinary Tract Cancer
Conditions
Bladder Cancer - Transitional Cell Cancer of the Renal Pelvis and Ureter - Ureter Cancer - Urethral Cancer
Conditions: official terms
Carcinoma, Transitional Cell - Kidney Neoplasms - Ureteral Neoplasms - Urinary Bladder Neoplasms
Conditions: Keywords
metastatic transitional cell cancer of the renal pelvis and ureter, regional transitional cell cancer of the renal pelvis and ureter, transitional cell carcinoma of the bladder, stage III bladder cancer, stage IV bladder cancer, anterior urethral cancer, posterior urethral cancer, urethral cancer associated with invasive bladder cancer, ureter cancer
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Intervention
Name: carboplatin Type: Drug
Name: gemcitabine hydrochloride Type: Drug
Name: vandetanib Type: Drug
Name: Placebo Type: Drug
Overall Status
Recruiting
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.
Detailed 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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: 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
Locations
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, United Kingdom
Status: Recruiting
Contact: Contact Person - 44-141-301-7095 - Rob.Jones@ggc.scot.nhs.uk
Wales Cancer Trials Unit
Cardiff, Wales, United Kingdom
Status: Recruiting
Contact: Contact Person - 44-29-2019-6800
Ayr Hospital
Ayr, United Kingdom
Status: Recruiting
Contact: Margaret McKernan - 01563 825749 - margaret.mckernan@aaaht.scot.nhs.uk
Royal Bournemouth General Hospital
Bournemouth, United Kingdom
Status: Recruiting
Contact: Susannah Brock - susannah.brock@poole.nhs.uk
Queens Hospital
Burton upon Trent, United Kingdom
Status: Recruiting
Contact: Pugazhenthi Pattu - 01332 340131 - pugazhenthi.pattu@nhs.net
Velindre Hospital
City and County of Cardiff, United Kingdom
Status: Recruiting
Contact: Dr Lester, Jason - 44-2920 196159 - jason.lester2@wales.nhs.uk
Western General Hospital
Edinburgh, United Kingdom
Status: Recruiting
Contact: Duncan McLaren - duncan.mclaren@luht.scot.nhs.uk
Calderdale Royal Infirmary
Halifax, United Kingdom
Status: Recruiting
Contact: Lisa Gledhill - 01484 342925 - lisa.gledhill@cht.nhs.uk
Huddersfield Royal Infirmary
Huddersfield, United Kingdom
Status: Recruiting
Contact: Uschi Hofmann - 0484 847299 - uschi.hofmann@cht.nhs.uk
The Royal Lancaster Infirmary
Lancaster, United Kingdom
Status: Recruiting
Contact: Alison Birtle - 01524 583219 - alison.birtle@lhtr.nhs.uk
St. James's University Hospital
Leeds, United Kingdom
Status: Recruiting
Contact: Satinder Jagdev - 0113 2067645 - satinder.jagdev@leedsth.nhs.uk
Charing Cross Hospital
London, United Kingdom
Status: Not yet recruiting
Contact: Simon Stewart - simon.stewart@imperial.nhs.uk
St Marys Hospital
London, United Kingdom
Status: Not yet recruiting
Contact: Gillian Hornzee - Gillian.Hornzee@imperial.nhs.uk
The Royal Free Hospital
London, United Kingdom
Status: Not yet recruiting
Christie Hospital
Manchester, United Kingdom
Status: Recruiting
Contact: Tony Eliott - 01619187214 - tony.eliott@christie.nhs.uk
Mount Vernon Hospital
Northwood Middlesex, United Kingdom
Status: Recruiting
Contact: Peter Hoskin - 01923 844533 - peter.hoskin@nhs.net
Churchill Hospital
Oxford, United Kingdom
Status: Recruiting
Contact: Georgina Rogers - patpandrewprotheroe@oncology.ox.ac.uk
Weston Park Hospital
Sheffield, United Kingdom
Status: Recruiting
Contact: Linda Evans - 0114 226500 - linda.evans@sth.nhs.uk
Southampton General Hospital
Southampton, United Kingdom
Status: Recruiting
Contact: Simon Crabb - s.j.crabb@southampton.ac.uk
Royal Surrey County Hospital
Surrey, United Kingdom
Status: Recruiting
Contact: Katie Wood - 01483 571122 - katiewood@nhs.net
The Royal Marsden Hospital
Surrey, United Kingdom
Status: Recruiting
Contact: Robert Huddart - 020 8661 3457 - robert.huddart@icr.ac.uk
Start Date
June 2010
Completion Date
December 2014
Sponsors
Wales Cancer Trials Unit
Source
Wales Cancer Trials Unit
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page