Gemcitabine Hydrochloride, Cisplatin, and Sunitinib Malate as First-Line Therapy in Treating Patients With Locally Advanced And/or Metastatic Transitional Cell Carcinoma of the Urothelium

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Cardiff University
Information provided by (Responsible Party):
Wales Cancer Trials Unit
ClinicalTrials.gov Identifier:
NCT01089088
First received: March 17, 2010
Last updated: February 28, 2013
Last verified: February 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sunitinib malate 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. Giving gemcitabine hydrochloride and cisplatin together with sunitinib malate may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving gemcitabine hydrochloride and cisplatin together with sunitinib malate and to see how well it works as first-line therapy in treating patients with locally advanced and/or metastatic transitional cell carcinoma of the urothelium.


Condition Intervention Phase
Bladder Cancer
Transitional Cell Cancer of the Renal Pelvis and Ureter
Urethral Cancer
Drug: cisplatin
Drug: gemcitabine hydrochloride
Drug: sunitinib malate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Single-Arm Trial to Evaluate Cisplatin and Gemcitabine Chemotherapy in Combination With Sunitinib for First-Line Treatment of Patients With Advanced Transitional Carcinoma of the Urothelium

Resource links provided by NLM:


Further study details as provided by Wales Cancer Trials Unit:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Proportion of patients progression free at 6 months


Secondary Outcome Measures:
  • Toxicity during and after treatment according to NCI CTCAE v 3.0 [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
  • Tolerability (side effects) and feasibility of use (number of patients requiring dose delays or reduction and/or treatment withdrawal) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Progression-free survival (time-to-event) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Objective (radiological) response rate according to RECIST [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 63
Study Start Date: April 2009
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: cisplatin

    Up to six 21 day chemotherapy cycles:

    Cisplatin 70mg/m2 (IV day 1) Gemcitabine 1000mg/m2 (IV days 1 & 8) Sunitinib 37.5mg (po days 2 to 15)

    Other Name: Sutent
    Drug: gemcitabine hydrochloride

    Up to six 21 day chemotherapy cycles:

    Cisplatin 70mg/m2 (IV day 1) Gemcitabine 1000mg/m2 (IV days 1 & 8) Sunitinib 37.5mg (po days 2 to 15)

    Drug: sunitinib malate

    Up to six 21 day chemotherapy cycles:

    Cisplatin 70mg/m2 (IV day 1) Gemcitabine 1000mg/m2 (IV days 1 & 8) Sunitinib 37.5mg (po days 2 to 15)

Detailed Description:

OBJECTIVES:

  • To determine the activity, safety, and feasibility of gemcitabine hydrochloride and cisplatin in combination with sunitinib malate as first-line therapy in patients with locally advanced and/or metastatic transitional carcinoma of the urothelium.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, cisplatin IV over 3-4 hours on day 1, and oral sunitinib malate once daily on days 2-15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 6 months and 1 year.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed transitional cell carcinoma of the urothelium

    • Pure or mixed histology
    • Upper or lower urinary tract
  • Radiologically measurable, locally advanced and/or metastatic disease not amenable to curative treatment with surgery or radiotherapy meeting 1 of the following criteria:

    • T4b (bladder) or T4 (renal pelvis/ureter), any N, any M
    • Any T, N2-3, any M
    • Any T, any N, M1
  • No urothelial cancer for which subsequent radical treatment is being considered with a view to possibly cure the disease
  • No history of CNS metastases

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • Life expectancy > 3 months
  • Absolute neutrophil count ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT and ALP ≤ 2.5 times ULN
  • GFR ≥ 60 mL/min (uncorrected for surface area and measured by isotopic means)
  • PT or INR ≤ 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Fit to receive cisplatin-containing combination chemotherapy
  • No previous malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, or incidental localized prostate cancer
  • No known HIV positivity or chronic hepatitis B or C infection
  • No uncontrolled hypertension
  • No symptomatic coronary artery disease, myocardial infarction within the past 6 months, congestive cardiac failure (NYHA class III-IV disease), or uncontrolled or symptomatic cardiac arrhythmia
  • No clinically significant bacterial or fungal infection
  • No concurrent grapefruit juice

PRIOR CONCURRENT THERAPY:

  • At least 1 month since prior radiotherapy or radiotherapy involving more than 30% of total bone marrow volume
  • At least 1 month since prior investigational drug
  • No prior systemic therapy for locally advanced or metastatic disease

    • Patients who have received prior neoadjuvant or adjuvant chemotherapy for urothelial cancer (up to 4 courses), completed at least 6 months prior to first documented disease progression, are eligible
  • No concurrent anticoagulant therapy with warfarin or unfractionated heparin

    • Patients requiring anticoagulation may be entered on study after successful conversion to low molecular weight heparin
  • No concurrent medications that have known adverse interactions with sunitinib malate (i.e., strong CYP3A4 inhibitors or inducers)
  • No prior or concurrent live vaccines (e.g., measles, mumps, rubella, oral polio, bacille Calmette-Guérin [BCG], yellow fever, varicella, and TY21a typhoid vaccines)
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01089088

Locations
United Kingdom
Bristol Haematology and Oncology Centre
Bristol, Avon, United Kingdom, BS2 8ED
Castle Hill Hospital
Cottingham, East Yorkshire, United Kingdom, HU16 5JQ
Royal Bournemouth Hospital
Bournemouth, England, United Kingdom, BH7 7DW
Churchill Hospital
Oxford, Oxfordshire, United Kingdom, OX3 7LJ
Royal Shrewsbury Hospital
Shrewsbury, Shropshire, United Kingdom, SY3 8XQ
The Royal Marsden Hospitals (Surrey)
Sutton, Surrey, United Kingdom, Surrey
St James's University Hospital
Leeds, Yorkshire, United Kingdom, LS9 7TF
Velindre Hospital
Cardiff, United Kingdom, CF14 2TL
Hammersmith Hospital
London, United Kingdom, W12 0HS
Charing Cross Hospital
London, United Kingdom, W6 8RF
St Mary's Hospital (Paddington)
London, United Kingdom, W2 1NY
Christie Hospital
Manchester, United Kingdom, M20 4BX
Southampton General Hospital
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
Wales Cancer Trials Unit
Cardiff University
Investigators
Principal Investigator: Tom Geldart Royal Bournemouth Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Wales Cancer Trials Unit
ClinicalTrials.gov Identifier: NCT01089088     History of Changes
Other Study ID Numbers: CDR0000667764, WCTU-SUCCINCT, ISRCTN54607216, EUDRACT-2007-007591-42, EU-21013, WCTU-SPON-416-07, CRUK-07/044
Study First Received: March 17, 2010
Last Updated: February 28, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Wales Cancer Trials Unit:
recurrent urethral cancer
recurrent transitional cell cancer of the renal pelvis and ureter
metastatic transitional cell cancer of the renal pelvis and ureter
regional transitional cell cancer of the renal pelvis and ureter
posterior urethral cancer
urethral cancer associated with invasive bladder cancer
transitional cell carcinoma of the bladder
stage IV bladder cancer
recurrent bladder cancer
anterior urethral cancer

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma
Carcinoma, Transitional Cell
Urethral Neoplasms
Kidney Neoplasms
Ureteral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urethral Diseases
Kidney Diseases
Ureteral Diseases
Gemcitabine
Sunitinib
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 26, 2014