Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Gefitinib Plus Combination Chemotherapy in Treating Patients With Locally Advanced or Metastatic Bladder Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	CALGB-90102 NCT00041106

Objectives

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

Entry 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

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

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count greater than 1,500/mm³
• Platelet count greater than 100,000/mm³

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

Expected Enrollment

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

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.

Philips GK, Halabi S, Sanford BL, et al.: 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 20 (6): 1074-9, 2009.[PUBMED Abstract]

Philips GK, Halabi S, Sanford BL, et al.: 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 101 (1): 20-5, 2008.[PUBMED Abstract]

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.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

George Philips, MD, MPH, Protocol chair		Ph: 802-847-3827; 800-358-1144

Registry Information
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
Trial Start Date		2002-07-17
Trial Completion Date		2009-05-14
Registered in ClinicalTrials.gov		NCT00041106
Date Submitted to PDQ		2002-05-22
Information Last Verified		2004-11-01
NCI Grant/Contract Number		U10-CA31946

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