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

NCT ID: NCT01191892

Last Updated: 2019-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2016-09-05

Brief 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.

Conditions

Bladder Cancer; Transitional Cell Cancer of the Renal Pelvis and Ureter; Ureter Cancer; Urethral Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Carboplatin, Gemcitabine and Placebo

Group Type: PLACEBO_COMPARATOR

carboplatin

Intervention Type: DRUG

gemcitabine hydrochloride

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Placebo of vandetanib tablet

vandetanib

Carboplatin, Gemcitabine and vandetanib

Group Type: EXPERIMENTAL

carboplatin

Intervention Type: DRUG

gemcitabine hydrochloride

Intervention Type: DRUG

vandetanib

Intervention Type: DRUG

Interventions

carboplatin

Intervention Type: DRUG

gemcitabine hydrochloride

Intervention Type: DRUG

vandetanib

Intervention Type: DRUG

Placebo

Placebo of vandetanib tablet

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cardiff University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Jones, MD

Role: PRINCIPAL_INVESTIGATOR

University of Glasgow

Locations

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, United Kingdom

Wales Cancer Trials Unit

Cardiff, Wales, United Kingdom

Ayr Hospital

Ayr, , United Kingdom

Royal Bournemouth General Hospital

Bournemouth, , United Kingdom

Queens Hospital

Burton-on-Trent, , United Kingdom

Velindre Hospital

City and County of Cardiff, , United Kingdom

Western General Hospital

Edinburgh, , 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

The Royal Free Hospital

London, , United Kingdom

St Marys Hospital

London, , United Kingdom

Charing Cross 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, , United Kingdom

Countries

United Kingdom

Other Identifiers

WCTU-TOUCAN

Identifier Type: -

Identifier Source: secondary_id

ISRCTN-68146831

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2009-010140-33

Identifier Type: -

Identifier Source: secondary_id

EU-21066

Identifier Type: -

Identifier Source: secondary_id

CRUK-09/024

Identifier Type: -

Identifier Source: secondary_id

WCTU-SPON-672-09

Identifier Type: -

Identifier Source: secondary_id

ZENECA-WCTU-TOUCAN

Identifier Type: -

Identifier Source: secondary_id

CDR0000684016

Identifier Type: -

Identifier Source: org_study_id