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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01191892
Recruitment Status : Completed
First Posted : August 31, 2010
Last Update Posted : May 16, 2019
Information provided by (Responsible Party):
Cardiff University

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.

Condition or disease Intervention/treatment Phase
Bladder Cancer Transitional Cell Cancer of the Renal Pelvis and Ureter Ureter Cancer Urethral Cancer Drug: carboplatin Drug: gemcitabine hydrochloride Drug: vandetanib Drug: Placebo Phase 2

Detailed Description:



  • 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.


  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Study Start Date : June 2010
Actual Primary Completion Date : December 2015
Actual Study Completion Date : September 5, 2016

Arm Intervention/treatment
Placebo Comparator: Placebo
Carboplatin, Gemcitabine and Placebo
Drug: carboplatin
Drug: gemcitabine hydrochloride
Drug: Placebo
Placebo of vandetanib tablet

Experimental: vandetanib
Carboplatin, Gemcitabine and vandetanib
Drug: carboplatin
Drug: gemcitabine hydrochloride
Drug: vandetanib

Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 1 year ]
    Time to event PFS, follow-up to 1 year

Secondary Outcome Measures :
  1. Tolerability and feasibility [ Time Frame: 1 year ]
    Rate of randomisation and safety profile of randomised patients

  2. Objective response rate as assessed by RECIST criteria [ Time Frame: Up to 1 year ]
    Proportion of patients responding to treatment

  3. Overall survival [ Time Frame: 2 years ]
    Patients will be followed up until death by using NHS flagging service.

  4. Change in size of measurable lesions 9 weeks after start of chemotherapy [ Time Frame: 9 weeks ]
  5. Toxicity during and after treatment as assessed by NCI CTCAE v 4.0 [ Time Frame: 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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)


  • 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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01191892

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Sponsors and Collaborators
Cardiff University
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Principal Investigator: Robert Jones, MD University of Glasgow
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Responsible Party: Cardiff University Identifier: NCT01191892    
Other Study ID Numbers: CDR0000684016
First Posted: August 31, 2010    Key Record Dates
Last Update Posted: May 16, 2019
Last Verified: May 2019
Keywords provided by Cardiff University:
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
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urethral Neoplasms
Carcinoma, Transitional Cell
Kidney Neoplasms
Ureteral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Urethral Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Diseases
Ureteral Diseases
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs