Title
Keyhole Limpet Hemocyanin Compared With Doxorubicin in Treating Patients With Bladder Cancer
A Randomized, Multicenter Phase III Trial Evaluating the Efficacy and Safety of BCI-ImmuneActivator Versus Adriamycin in BCG Refractory or Intolerant Patients With Carcinoma in Situ With or Without Resected Superficial Papillary Bladder Cancer
Phase
Phase 3Lead Sponsor
IntracelStudy Type
InterventionalStatus
Completed No Results PostedIndication/Condition
Bladder CancerIntervention/Treatment
doxorubicin keyhole limpet hemocyanin ...Study Participants
NoneRATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether keyhole limpet hemocyanin is more effective than doxorubicin for bladder cancer.
PURPOSE: Randomized phase III trial to compare the effectiveness of keyhole limpet hemocyanin with that of doxorubicin in treating patients who have bladder cancer that has not responded to BCG or in those patients who cannot tolerate BCG.
OBJECTIVES:
Compare the efficacy of BCI-ImmuneActivator™ (keyhole limpet hemocyanin) versus doxorubicin in BCG refractory or intolerant patients with carcinoma in situ with or without resected superficial papillary bladder cancer.
Compare the toxicity and safety of these treatments in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and prior BCG response (refractory vs intolerant). Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive a sensitizing dose of keyhole limpet hemocyanin (KLH) intradermally at week -2 followed by induction KLH IV once weekly at weeks 1-6. Patients with partial or no response receive IV KLH reinduction therapy once weekly at weeks 13-18. Patients with complete response receive IV KLH maintenance therapy monthly at weeks 13, 17, and 21, and then at months 6-12.
Arm II: Patients receive doxorubicin IV once weekly at weeks 1-6. Patients with complete response receive maintenance therapy comprising doxorubicin IV at weeks 13, 17, and 21 and months 6-12.
Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 1.5 years, and then every 6 months for 1 year. (Patient total participation in this study may last as long as 42 months.)
PROJECTED ACCRUAL: A total of 150 patients (75 per treatment arm) will be accrued for this study.
Given intradermally and IV
Given IV
Patients receive a sensitizing dose of keyhole limpet hemocyanin (KLH) intradermally in week 2 followed by induction KLH IV once weekly in weeks 1-6. Patients with partial or no response receive IV KLH reinduction therapy once weekly in weeks 13-18. Patients with complete response receive IV KLH maintenance therapy monthly in weeks 13, 17, and 21, and then in months 6-12.
Patients receive doxorubicin IV once weekly in weeks 1-6.
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed carcinoma in situ of the bladder with or without resected superficial papillary tumor Biopsy within 3 months of study with or without positive urinary cytology within 6 weeks of study Cystoscopy within 3 months of study Negative imaging study of the ureters and kidneys within 6 months of study BCG refractory disease Received and failed at least 1 prior induction course consisting of BCG weekly for 6 weeks OR BCG intolerant Unable to receive an adequate course of intravesical BCG due to extreme toxicity Opted against or medically contraindicated to cystectomy PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 OR Karnofsky 60-100% Life expectancy Not specified Hematopoietic WBC greater than 4,000/mm^3 Platelet count greater than 100,000/mm^3 Hemoglobin greater than 11 g/dL Hepatic Bilirubin normal SGOT/SGPT normal Renal Creatinine no greater than 1.5 times upper limit of normal Cardiovascular No severe cardiovascular disease Other No other severe disease No other malignancy within the past 5 years except basal or squamous cell skin cancer or noninvasive cancer of the cervix No evidence of autoimmune disease, known immune deficiency, or immunosuppression Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics No prior keyhole limpet hemocyanin immune activator Chemotherapy No prior doxorubicin At least 3 months since prior mitomycin No other concurrent chemotherapy Endocrine therapy No concurrent steroids Radiotherapy At least 4 months since prior radiotherapy Surgery See Disease Characteristics Other At least 4 weeks since prior intravesical therapy At least 3 months since prior investigational agents No concurrent cytotoxic immunosuppressive agents
