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Gefitinib Plus Combination Chemotherapy in Treating Patients With Locally Advanced or Metastatic Bladder Cancer
This study has been completed.

First Received on July 8, 2002.   Last Updated on March 22, 2011   History of Changes
Sponsor: Cancer and Leukemia Group B
Collaborator: National Cancer Institute (NCI)
Information provided by: Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00041106
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of the tumor. Combining chemotherapy with gefitinib may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy with gefitinib in treating patients who have metastatic transitional cell cancer of the urothelium.


Condition Intervention Phase
Bladder Cancer
Renal Pelvis and Ureter Urothelial Carcinoma
Urethral Cancer
Drug: cisplatin
Drug: Iressa
Drug: gemcitabine hydrochloride
Phase II

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Of Cisplatin, Gemcitabine, And ZD 1839 (IRESSA) (IND #61187; NSC 715055) For The Treatment Of Advanced Urothelial Tract Carcinoma

Resource links provided by NLM:


Further study details as provided by Cancer and Leukemia Group B:

Primary Outcome Measures:
  • Overall response [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: q ea cycle (6 cycles total) ] [ Designated as safety issue: Yes ]

Enrollment: 85
Study Start Date: July 2002
Study Completion Date: June 2010
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cisplatin, Gemcitabine, & Iressa
Addition of experimental agent iressa (ZD1839) to chemotherapy treatment for advanced urothelial tract cancer
Drug: cisplatin
70 mg/sq m IV over 1 hour on Day 1 of each cycle
Drug: Iressa
500 mg/day PO ea cycle and daily for up to 5 years if no progression after 6 cycles
Other Name: gefitinib; ZD 1839
Drug: gemcitabine hydrochloride
1000 mg/sq m IV over 30 min on Days 1 & 8 of each cycle

Detailed Description:

OBJECTIVES:

  • Determine the overall response rate in patients with metastatic transitional cell carcinoma of the urothelium treated with cisplatin, gemcitabine, and gefitinib.
  • Determine the time to progression, progression-free survival, and overall survival in patients treated with this regimen.
  • Determine the effect of epidermal growth factor receptor expression level on overall response rate and progression-free survival in patients treated with this regimen.
  • Determine the toxicity of this regimen in this patient population.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and cisplatin IV over 1 hour on day 1. Patients also receive oral gefitinib once daily beginning on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete remission, partial remission, or maintain stable disease continue oral gefitinib once daily for 5 years or until disease progression or unacceptable toxicity occurs.

Patients are followed at least every 3 months for 1 year and then at least every 6 months until disease progression or relapse.

PROJECTED ACCRUAL: A total of 12-50 patients will be accrued for this study within 12-18 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed transitional cell carcinoma of the urothelium (bladder, ureter, renal pelvis or urethra)

    • Metastatic disease (N2, N3, or M1)
    • Histologic confirmation of metastatic/recurrent disease is not required
  • Not amenable to potentially curative surgery or radiotherapy
  • At least 1 unidimensionally measurable lesion

    • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
    • Bladder not considered a site of measurable disease
    • Nonmeasurable lesions include:

      • Bone lesions
      • Leptomeningeal disease
      • Ascites
      • Pleural/pericardial effusion
      • Inflammatory breast disease
      • Lymphangitis cutis/pulmonis
      • Abdominal masses that are not confirmed and followed by imaging techniques
      • Cystic lesions
  • No evidence of brain metastases

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • Granulocyte count greater than 1,500/mm^3
  • Platelet count greater than 100,000/mm^3

Hepatic:

  • Bilirubin less than 1.25 times upper limit of normal (ULN)
  • AST/ALT less than 2 times ULN
  • No active severe chronic liver disease

Renal:

  • Creatinine clearance greater than 50 mL/min

Cardiovascular:

  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No pre-existing sensory or motor neuropathy greater than grade 1
  • No ongoing or active infection
  • No active severe chronic gastrointestinal disorders, including diarrheal or emetic disorders or malabsorptive conditions causing nausea or diarrhea
  • No active severe chronic desquamative cutaneous disorders
  • No active severe corneal disease or inflammatory ocular disorders
  • No other concurrent active malignancy except nonmelanoma skin cancer
  • HIV negative
  • No psychiatric illness or social situations that would preclude compliance
  • No other uncontrolled concurrent illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior systemic therapies for advanced carcinoma of the urothelium, including investigational agents targeting the HER2/neu, signal transduction, angiogenic, immune, and cell cycle pathways
  • No concurrent immunotherapy

Chemotherapy:

  • No prior systemic chemotherapy except single-agent chemotherapy used as a radiosensitizer
  • No prior adjuvant or neoadjuvant chemotherapy
  • Prior intravesical chemotherapy allowed
  • More than 4 weeks since prior intravesical chemotherapy and recovered
  • No other concurrent chemotherapy

Endocrine therapy:

  • More than 7 days since prior dexamethasone
  • No concurrent hormonal therapy except:

    • Steroids for adrenal failure
    • Hormones for nondisease-related conditions (e.g., insulin for diabetes)
    • Intermittent use of dexamethasone as an antiemetic

Radiotherapy:

  • See Disease Characteristics
  • More than 4 weeks since prior radiotherapy and recovered
  • No concurrent radiotherapy, including palliative radiotherapy

Surgery:

  • More than 4 weeks since prior major surgery and recovered

Other:

  • No prior gefitinib
  • No prior investigational epidermal growth factor receptors for advanced carcinoma of the urothelium
  • More than 7 days since prior CYP3A4 inducers, including phenytoin, carbamazepine, barbiturates, rifampin, Hypericum perforatum, modafinil, or rifapentine
  • No concurrent CYP3A4 inducers, including phenytoin, carbamazepine, barbiturates, rifampin, Hypericum perforatum, modafinil, or rifapentine
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00041106

  Show 82 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: George Philips, MD, MPH Fletcher Allen Health Care - University Health Center Campus
  More Information

Additional Information:
Publications:
Philips GK, Halabi S, Sanford BL, Bajorin D, Small EJ; for the Cancer and Leukemia Group B. A phase II trial of cisplatin (C), gemcitabine (G) and gefitinib for advanced urothelial tract carcinoma: results of Cancer and Leukemia Group B (CALGB) 90102. Ann Oncol. 2009 Jan 23; [Epub ahead of print]
Philips GK, Halabi S, Sanford BL, Bajorin D, Small EJ; Cancer and Leukaemia Group B. A phase II trial of cisplatin, fixed dose-rate gemcitabine and gefitinib for advanced urothelial tract carcinoma: results of the Cancer and Leukaemia Group B 90102. BJU Int. 2007 Oct 8; [Epub ahead of print]
Philips G, Sanford B, Halabi S, et al.: Phase II study of cisplatin (C), gemcitabine (G) and gefitinib for advanced urothelial carcinoma (UC): analysis of the second cohort of CALGB 90102. [Abstract] J Clin Oncol 24 (Suppl 18): A-4578, 2006.
Philips G, Halabi S, Sanford B, et al.: Phase II trial of cisplatin (C), fixed-dose rate gemcitabine (G) and gefitinib for advanced transitional cell carcinoma (TCC) of the urothelial tract: preliminary results of CALGB 90102. [Abstract] J Clin Oncol 22 (Suppl 14): A-4540, 391s, 2004.

Responsible Party: Monica M Bertagnolli, MD, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00041106     History of Changes
Other Study ID Numbers: CDR0000069443, U10CA031946, CALGB-90102
Study First Received: July 8, 2002
Last Updated: March 22, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Cancer and Leukemia Group B:
recurrent bladder cancer
stage IV bladder cancer
transitional cell carcinoma of the bladder
recurrent urethral cancer
anterior urethral cancer
posterior urethral cancer
urethral cancer associated with invasive bladder cancer
metastatic transitional cell cancer of the renal pelvis and ureter
recurrent transitional cell cancer of the renal pelvis and ureter

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
Gefitinib
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 February 12, 2012