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

Alternate Title

BCG With or Without Gefitinib in Treating Patients With High-Risk Bladder Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 and over Other CAN-NCIC-BL11 NCT00352079, BL11

Objectives

Primary

1. Compare the impact of gefitinib and intravesical BCG vs intravesical BCG alone on time to treatment failure in patients with high-risk, superficial transitional cell carcinoma of the bladder.

Secondary

1. Compare the complete response rates in patients with carcinoma in situ receiving gefitinib and intravesical BCG vs patients receiving intravesical BCG alone.
2. Compare the time to recurrence in patients treated with these regimens.
3. Compare the time to progression in patients treated with these regimens.
4. Compare the overall survival of patients treated with these regimens.
5. Characterize and contrast the adverse event and safety profile of these regimens in these patients.
6. Compare the effects of these regimens on quality of life in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed transitional cell carcinoma (TCC) of the bladder meeting ≥ 1 of the following criteria:
  • Noninvasive papillary carcinoma (Ta) with ≥ 1 of the following characteristics:
    • Recurrence of bladder tumor(s) ≥ grade 2 within 6 months after transurethral resection (TUR)
    • Three or more bladder tumors ≥ grade 2 at the time of TUR
    • Bladder tumor(s) ≥ 5 cm in size and ≥ grade 2 at the time of TUR
    • Any grade 3 bladder tumor(s)
  • Carcinoma in situ (Tis)
  • At least grade 2 tumor that invades the subepithelial connective tissue (T1)



• Has undergone TUR of all visible bladder lesions within the past 21 to 60 days with biopsy of the underlying bladder wall for all tumors and cold-cup biopsy of all suspicious areas



• No metastatic disease as confirmed by negative radiology within the past 16 weeks, including the following:
  • Chest x-ray
  • Imaging of the upper urinary tract by 1 of the following methods:
    • CT scan, MRI, or ultrasound of the abdomen and pelvis
    • Intravenous pyelogram
    • Retrograde pyelogram



• No evidence of TCC of the upper urinary tract



• No mixed histology of bladder cancer (i.e., TCC and squamous cell carcinoma of the bladder or TCC and small cell carcinoma of the bladder) at the most recent TUR

Prior/Concurrent Therapy:

• See Disease Characteristics
• More than 12 months since prior intravesical immunotherapy (including BCG +/- interferon)
• More than 6 months since prior intravesical chemotherapy (including mitomycin C, thiotepa, doxorubicin hydrochloride)
  • Single dose of intravesical mitomycin C at the time of the most recent TUR (within the past 21 to 60 days) allowed if considered standard care
• No other prior or concurrent immune modulator therapy
• No prior pelvic radiation
• No prior gefitinib
• No other concurrent experimental anticancer drugs
• No concurrent use of drugs that induce CYP3A4 enzymes that have been shown to significantly reduce plasma concentrations of gefitinib (including phenytoin, carbamazepine, barbiturates, rifampin, or Hypericum perforatum [St. John's wort])
• No concurrent grapefruit juice

Patient Characteristics:

• ECOG performance status 0-2
• Life expectancy > 5 years
• Negative routine urine microscopy and negative urine culture within the past 14 days
• Willing to complete quality of life questionnaires in English or French
  • Inability to complete questionnaires due to illiteracy in English or French, loss of sight, or other reason allowed
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 1.5 times ULN
• Alkaline phosphatase ≤ 1.5 times ULN
• Creatinine ≤ 1.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study completion
• No significant history of cardiac disease including, but not limited to, any of the following:
  • Uncontrolled high blood pressure
  • Unstable angina
  • Congestive heart failure
  • Myocardial infarction within the past year
  • Cardiac ventricular arrhythmias requiring medication
• No active urinary tract infection
• No active infection, including tuberculosis
• No serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment
• No febrile illness or gross hematuria
• No impaired immune response from any cause (congenital, therapy, or disease)
• No clinically significant or untreated ophthalmologic condition (e.g., Sjögren's syndrome)
• No gastrointestinal conditions (e.g., Crohn’s disease or ulcerative colitis)
• No history of psychiatric or neurological disorder that would limit study compliance
• No other malignancies except for adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
• No contraindications to spinal or general anesthesia as required for a TUR
• No known hypersensitivity to BCG or gefitinib
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs

Expected Enrollment

A total of 166 patients will be accrued for this study.

Outcomes

Time to treatment failure

Complete response rate in patients with carcinoma in situ
Time to recurrence
Time to progression
Overall survival
Adverse event and safety profile
Quality of life

Outline

This is a randomized, prospective, open-label, controlled, multicenter study. Patients are stratified according to study center, status of tumor (primary vs recurrent), carcinoma in situ (yes vs no), prior BCG therapy (yes vs no), and single dose of intravesical mitomycin C at the time of the most recent transurethral resection (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive induction therapy comprising intravesical BCG once weekly for 6 weeks. Patients then receive maintenance therapy comprising intravesical BCG once weekly for 3 weeks.



• Arm II: Patients receive induction therapy comprising intravesical BCG once weekly for 6 weeks and oral gefitinib once daily for 12 weeks. Patients then receive maintenance therapy comprising intravesical BCG once weekly for 3 weeks and oral gefitinib once daily for 12 weeks.

In both arms, treatment with maintenance therapy repeats at 3, 6, 12, 18, 24, 30, and 36 months for a total of 7 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, periodically during study therapy, and then at 3 and 6 months after completion of study therapy.

After study completion, patients are followed every 3 months for 2 years, every 6 months for 4 years, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

NCIC-Clinical Trials Group

Louis Lacombe, MD, Protocol chair		Ph: 418-691-5561 Email: louis.lacombe@crhdq.ulaval.ca

Canada
British Columbia
	Vancouver
	University of British Columbia
		Alan I. So	Ph:  604-875-4111
Ontario
	Hamilton
	McMaster Institute of Urology at St. Joseph Healthcare
		Anil Kapoor	Ph:  905-522-6536
	London
	London Regional Cancer Program at London Health Sciences Centre
		Jonathan Izawa	Ph:  519-685-8550
	Toronto
	Princess Margaret Hospital
		Michael A.S. Jewett	Ph:  416-946-2909
Quebec
	Quebec City
	Centre Hospitalier Universitaire de Quebec
		Louis Lacombe	Ph:  418-691-5O50
	Sherbrooke
	CHUS-Hopital Fleurimont
		Michel Carmel	Ph:  819-346-1110

Registry Information
Official Title		A Phase III Study of IRESSA® in Combination with Intravesical BCG Versus Intravesical BCG Alone in High Risk Superficial Transitional Cell Carcinoma of the Bladder
Trial Start Date		2006-04-12
Trial Completion Date		2012-04-12 (estimated)
Registered in ClinicalTrials.gov		NCT00352079
Date Submitted to PDQ		2006-05-19
Information Last Verified		2008-02-26