This pilot clinical trial studies how well gemcitabine hydrochloride, cisplatin, and AGS-003-BLD work in treating patients with bladder cancer that has spread to the muscle and who are undergoing surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Vaccines made from a person's tumor cells may help the body build an effective immune response to kill tumor cells. Giving gemcitabine hydrochloride, cisplatin, and AGS-003-BLD before surgery may make the tumor smaller and reduce the amount of tissue that needs to be removed by surgery.
PRIMARY OBJECTIVES: I. To assess the immunogenicity of AGS-003-BLD in subjects with muscle invasive bladder cancer. SECONDARY OBJECTIVES: I. To assess 1-year disease-free survival rate of patients with muscle-invasive bladder cancer who receive cisplatin/gemcitabine chemotherapy plus AGS-003-BLD. II. To determine the time to first metastatic lesion. III. To explore the disease-free and overall survival of patients treated with this treatment combination. IV. To evaluate the pathologic complete response (pCR) rate and identify any activity of this treatment combination. V. To evaluate toxicities and tolerability associated with this treatment combination. VI. To assess the success rate of tumor procurement and AGS-003-BLD production of \>= 5 doses. TERTIARY OBJECTIVES: I. To evaluate the relationships between pathologic complete response with the change in CD28+ T cell levels. II. To evaluate the change in frequency of CD11a highPD-1+ CD8+ T cells (and their expression of Bim) in peripheral blood. OUTLINE: NEOADJUVANT PHASE: Patients receive gemcitabine hydrochloride intravenously (IV) on days 1 and 8, AGS-003-BLD intradermally (ID) on day 1, and cisplatin IV on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive AGS-003-BLD ID on day 1. Treatment repeats every 14 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo cystectomy during course 8. ADJUVANT PHASE: Patients continue AGS-003-BLD ID on day 1 of course 9. Treatment repeats every 12 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
Mayo Clinic
Rochester, Minnesota, United States
Change in the frequency of CD11a high PD-1+ CD8+ T cells
Descriptive statistics (mean, standard deviation \[sd\], median, interquartile range \[iqr\]) will be used to summarize change from baseline in the frequency of CD11a high PD-1+ CD8+ T cells following five doses of AGS-003-BLD.
Time frame: Baseline, before systemic therapy with chemotherapy
Change in the frequency of CD11a high PD-1+ CD8+ T cells
Descriptive statistics (mean, standard deviation \[sd\], median, interquartile range \[iqr\]) will be used to summarize change from baseline in the frequency of CD11a high PD-1+ CD8+ T cells following five doses of AGS-003-BLD.
Time frame: Prior to 1st dose of AGS-003-Bladder therapy
Change in the frequency of CD11a high PD-1+ CD8+ T cells
Descriptive statistics (mean, standard deviation \[sd\], median, interquartile range \[iqr\]) will be used to summarize change from baseline in the frequency of CD11a high PD-1+ CD8+ T cells following five doses of AGS-003-BLD.
Time frame: Treatment visit 7 (Cycle 3) After 3rd dose of AGS-003-Bladder therapy, up to 7 days
Change in the frequency of CD11a high PD-1+ CD8+ T cells
Descriptive statistics (mean, standard deviation \[sd\], median, interquartile range \[iqr\]) will be used to summarize change from baseline in the frequency of CD11a high PD-1+ CD8+ T cells following five doses of AGS-003-BLD.
Time frame: Treatment visit 15 (Cycle 6) - After the 5th dose of neoadjuvant AGS-003-Bladder therapy, up to 14 days
Change in the frequency of CD11a high PD-1+ CD8+ T cells
Descriptive statistics (mean, standard deviation \[sd\], median, interquartile range \[iqr\]) will be used to summarize change from baseline in the frequency of CD11a high PD-1+ CD8+ T cells following five doses of AGS-003-BLD.
Time frame: Treatment visit 20 (Cycle 8) - After the 8th dose (3rd adjuvant) of AGS-003 - Bladder therapy, up to 12 weeks
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NA
Purpose
TREATMENT
Masking
NONE
Given AGS-003-BLD ID
1-year survival rate
Time frame: 1 year
2-year disease-free survival rate
Time frame: 2 years
2-year survival rate
Time frame: 2 years
Disease-free survival rate
Time frame: 1 year
Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events
The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns.
Time frame: Up to 2 years
Manufacturing success rate and successful manufacture of > 5 doses and administration of 1 or more doses of AGS-003-BLD
Descriptive statistics (frequency table) and histogram will be used to summarize the success rate.
Time frame: Up 2 years
Proportion of pathologic complete responses
Descriptive statistics (frequency table) and histogram will be used to summarize the pathologic complete response rate.
Time frame: Up to 2 years
Time to first metastatic lesion
Will be estimated using the Kaplan-Meier method.
Time frame: Time from randomization to first recognition of metastases, assessed up to 2 years