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

NCT01191892 | Completed Phase 2 DMC

• 8 other identifiers: CDR0000684016WCTU-TOUCANISRCTN-68146831EUDRACT-2009-010140-33EU-21066CRUK-09/024WCTU-SPON-672-09ZENECA-WCTU-TOUCAN
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 21

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.

Conditions

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

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

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Time to event PFS, follow-up to 1 year

  1 year

Secondary Outcomes (5)

• Tolerability and feasibility

  1 year

• Objective response rate as assessed by RECIST criteria

  Up to 1 year

• Overall survival

  2 years

• Change in size of measurable lesions 9 weeks after start of chemotherapy

  9 weeks

• Toxicity during and after treatment as assessed by NCI CTCAE v 4.0

  1 year

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Carboplatin, Gemcitabine and Placebo

Drug: carboplatin; Drug: gemcitabine hydrochloride; Drug: Placebo

vandetanib

EXPERIMENTAL

Carboplatin, Gemcitabine and vandetanib

Drug: carboplatin; Drug: gemcitabine hydrochloride; Drug: vandetanib

Interventions

carboplatin DRUG

Placebo; vandetanib

gemcitabine hydrochloride DRUG

Placebo; vandetanib

vandetanib DRUG

vandetanib

Placebo DRUG

Placebo of vandetanib tablet

Placebo

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Cardiff University: lead

Study Sites (21)

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Wales Cancer Trials Unit

Cardiff, Wales, CF11 9LJ, United Kingdom

Location

Ayr Hospital

Ayr, KA66DX, United Kingdom

Location

Royal Bournemouth General Hospital

Bournemouth, BH7 7DW, United Kingdom

Location

Queens Hospital

Burton-on-Trent, DE13 0RB, United Kingdom

Location

Velindre Hospital

City and County of Cardiff, CF142TL, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Calderdale Royal Infirmary

Halifax, HX30PW, United Kingdom

Location

Huddersfield Royal Infirmary

Huddersfield, HD3 3EA, United Kingdom

Location

The Royal Lancaster Infirmary

Lancaster, LA1 4RP, United Kingdom

Location

St. James's University Hospital

Leeds, LS9 7TF, United Kingdom

Location

The Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

St Marys Hospital

London, W21NY, United Kingdom

Location

Charing Cross Hospital

London, W68RF, United Kingdom

Location

Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Mount Vernon Hospital

Northwood Middlesex, HA6 2RN, United Kingdom

Location

Churchill Hospital

Oxford, OX37LJ, United Kingdom

Location

Weston Park Hospital

Sheffield, S102SJ, United Kingdom

Location

Southampton General Hospital

Southampton, S016 6YD, United Kingdom

Location

Royal Surrey County Hospital

Surrey, GU27XX, United Kingdom

Location

The Royal Marsden Hospital

Surrey, KT2 7QB, United Kingdom

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Ureteral Neoplasms; Urethral Neoplasms

Interventions

Carboplatin; Gemcitabine; vandetanib

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Ureteral Diseases; Urethral Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Robert Jones, MD

  University of Glasgow

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2010
• First Posted: August 31, 2010
• Study Start: June 1, 2010
• Primary Completion: December 1, 2015
• Study Completion: September 5, 2016
• Last Updated: May 16, 2019

Record last verified: 2019-05

Locations

GB (21)