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

NCT00352079 | Terminated Phase 3 DMC

• 3 other identifiers: BL11CAN-NCIC-BL11CDR0000486873
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 6

Brief Summary

RATIONALE: Biological therapies, such as BCG, may stimulate the immune system in different ways and stop tumor cells from growing. Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving BCG together with gefitinib may kill more tumor cells. It is not yet known whether BCG is more effective with or without gefitinib in treating bladder cancer. PURPOSE: This randomized phase III trial is studying BCG and gefitinib to see how well they work compared to BCG alone in treating patients with high-risk bladder cancer.

Conditions

Bladder Cancer

Keywords

transitional cell carcinoma of the bladder; stage 0 bladder cancer; stage I bladder cancer; recurrent bladder cancer

Outcome Measures

Primary Outcomes (1)

• Time to treatment failure

  5 years

Secondary Outcomes (6)

• Complete response rate in patients with carcinoma in situ

  5 years

• Time to recurrence

  5 years

• Time to progression

  5 years

• Overall survival

  5 years

• Adverse event and safety profile

  5 years

Study Arms (2)

Intravesicle BCG

ACTIVE COMPARATOR

Induction: q weekly x 6 (cycle 1) Maintenance: q weekly x 3 at 3, 6, 12, 18, 24, 30, 36 months postrandomization (cycles 2 - 8)

Biological: BCG vaccine; Procedure: quality-of-life assessment

Iressa and Intravesicle BCG

ACTIVE COMPARATOR

Intravesical BCG: Induction: q weekly x 6 (cycle 1) Maintenance: q weekly x 3 at 3, 6, 12, 18, 24, 30, 36 months post- 2 randomization (cycles 2 - 8) Iressa® 250 mg PO Daily for 12 weeks starting on day 1 of each cycle of intravesical BCG therapy (cycles 1 - 8)

Biological: BCG vaccine; Drug: gefitinib; Procedure: quality-of-life assessment

Interventions

BCG vaccine BIOLOGICAL

Intravesical BCG: Induction: q weekly x 6 (cycle 1) Maintenance: q weekly x 3 at 3, 6, 12, 18, 24, 30, 36 months post- 2 randomization (cycles 2 - 8)

Intravesicle BCG; Iressa and Intravesicle BCG

gefitinib DRUG

Iressa® 250 mg PO Daily for 12 weeks starting on day 1 of each cycle of intravesical BCG therapy (cycles 1 - 8)

Iressa and Intravesicle BCG

quality-of-life assessment PROCEDURE

Each cycle and at 3 and 6 months after treatment discontinuation

Intravesicle BCG; Iressa and Intravesicle BCG

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 (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 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 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

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

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead

Study Sites (6)

Clinical Research Unit at Vancouver Coastal

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Hamilton and District Urology Association

Hamilton, Ontario, L8N 4A6, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

BCG Vaccine; Gefitinib

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

Intervention Hierarchy (Ancestors)

Tuberculosis Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Louis Lacombe, MD

  Centre Hospitalier Universitaire de Quebec

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2006
• First Posted: July 14, 2006
• Study Start: January 4, 2007
• Primary Completion: January 6, 2012
• Study Completion: January 6, 2012
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6)