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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 recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified July 2012 by Wales Cancer Trials Unit.
Recruitment status was:  Recruiting
Sponsor:
Collaborator:
Cardiff University
Information provided by (Responsible Party):
Wales Cancer Trials Unit
ClinicalTrials.gov Identifier:
NCT01191892
First received: August 29, 2010
Last updated: July 30, 2012
Last verified: July 2012
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Wales Cancer Trials Unit:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Time to event PFS, follow-up to 1 year


Secondary Outcome Measures:
  • Tolerability and feasibility [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Rate of randomisation and safety profile of randomised patients

  • Objective response rate as assessed by RECIST criteria [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Proportion of patients responding to treatment

  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Patients will be followed up until death by using NHS flagging service.

  • Change in size of measurable lesions 9 weeks after start of chemotherapy [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Toxicity during and after treatment as assessed by NCI CTCAE v 4.0 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 122
Study Start Date: June 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01191892

Locations
United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, United Kingdom, G12 0YN
Wales Cancer Trials Unit
Cardiff, Wales, United Kingdom, CF11 9LJ
Ayr Hospital
Ayr, United Kingdom, KA66DX
Royal Bournemouth General Hospital
Bournemouth, United Kingdom, BH7 7DW
Queens Hospital
Burton upon Trent, United Kingdom, DE13 0RB
Velindre Hospital
City and County of Cardiff, United Kingdom, CF142TL
Western General Hospital
Edinburgh, United Kingdom, EH4 2XU
Calderdale Royal Infirmary
Halifax, United Kingdom, HX30PW
Huddersfield Royal Infirmary
Huddersfield, United Kingdom, HD3 3EA
The Royal Lancaster Infirmary
Lancaster, United Kingdom, LA1 4RP
St. James's University Hospital
Leeds, United Kingdom, LS9 7TF
The Royal Free Hospital
London, United Kingdom, NW3 2QG
St Marys Hospital
London, United Kingdom, W21NY
Charing Cross Hospital
London, United Kingdom, W68RF
Christie Hospital
Manchester, United Kingdom, M20 4BX
Mount Vernon Hospital
Northwood Middlesex, United Kingdom, HA6 2RN
Churchill Hospital
Oxford, United Kingdom, OX37LJ
Weston Park Hospital
Sheffield, United Kingdom, S102SJ
Southampton General Hospital
Southampton, United Kingdom, S016 6YD
Royal Surrey County Hospital
Surrey, United Kingdom, GU27XX
The Royal Marsden Hospital
Surrey, United Kingdom, KT2 7QB
Sponsors and Collaborators
Wales Cancer Trials Unit
Cardiff University
Investigators
Principal Investigator: Robert Jones, MD University of Glasgow
  More Information

Responsible Party: Wales Cancer Trials Unit
ClinicalTrials.gov Identifier: NCT01191892     History of Changes
Other Study ID Numbers: CDR0000684016  WCTU-TOUCAN  ISRCTN-68146831  EUDRACT-2009-010140-33  EU-21066  CRUK-09/024  WCTU-SPON-672-09  ZENECA-WCTU-TOUCAN 
Study First Received: August 29, 2010
Last Updated: July 30, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Wales Cancer Trials Unit:
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:
Urinary Bladder Neoplasms
Urethral Neoplasms
Carcinoma, Transitional Cell
Kidney Neoplasms
Ureteral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Urethral Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Diseases
Ureteral Diseases
Gemcitabine
Carboplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 06, 2016