Infiltrating Bladder Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma, Stage III Bladder Urothelial Carcinoma, Stage IV Bladder Urothelial Carcinoma
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGCisplatin
Given IV
DRUGGemcitabine Hydrochloride
Given IV
PROCEDURERadical Cystectomy
Undergo cystectomy
BIOLOGICALTumor Cell-Derived Vaccine Therapy
Given AGS-003-BLD ID
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* PRE-REGISTRATION INCLUSION CRITERIA: Diagnosis or clinical signs of urothelial carcinoma with clinical stage T2 or greater disease without lymph node involvement where neoadjuvant chemotherapy of cisplatin and gemcitabine are indicated * PRE-REGISTRATION INCLUSION CRITERIA: Scheduled for a transurethral resection of bladder tumor (TURBT) * PRE-REGISTRATION INCLUSION CRITERIA: Be a candidate for radical cystectomy * PRE-REGISTRATION INCLUSION CRITERIA: Signed and dated informed consent document for study participation * PRE-REGISTRATION INCLUSION CRITERIA: Willing to submit tissue for required correlative research * REGISTRATION INCLUSION CRITERIA * TURBT successfully completed * Verification received from Argos Therapeutics that ribonucleic acid (RNA) successfully collected from TURBT procedure * Be a candidate for radical cystectomy * Diagnosis of urothelial carcinoma with stage T2 or greater disease without lymph node involvement where neoadjuvant chemotherapy of cisplatin and gemcitabine are indicated * Absolute neutrophil count (ANC) \>= 1500/uL * Platelet count \>= 100,000/uL * Total bilirubin =\< 1.5 x institutional upper normal limit (UNL) or =\< 3 x institutional UNL if known Gilbert's syndrome * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x UNL * Alkaline phosphatase =\< 5 x UNL * Hemoglobin \>= 9.0 g/dL * International normalized ratio (INR) and partial thromboplastin time (PTT) =\< 3.0 x UNL; NOTE: anticoagulation is allowed if target INR =\< 3.0 x UNL on a stable dose of warfarin or on a stable dose of low molecular weight heparin for \> 2 weeks at time of registration * Calculated creatinine clearance must be \>= 50 ml/min using the applicable Cockcroft-Gault formula * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 * Ability to provide written informed consent * Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures * Willing to provide tissue and blood samples for correlative research purposes * Negative serum pregnancy test for female subjects with reproductive potential =\< 7 days prior to registration, for women of childbearing potential only * Able to abstain from taking prohibited drugs, either prescription or non-prescription, during the treatment phase of the study
Exclusion criteria
* RE-REGISTRATION
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the frequency of CD11a high PD-1+ CD8+ T cells | Baseline, before systemic therapy with chemotherapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1-year survival rate | 1 year | — |
| 2-year disease-free survival rate | 2 years | — |
| 2-year survival rate | 2 years | — |
| Disease-free survival rate | 1 year | — |
| Proportion of pathologic complete responses | Up to 2 years | Descriptive statistics (frequency table) and histogram will be used to summarize the pathologic complete response rate. |
| Time to first metastatic lesion | Time from randomization to first recognition of metastases, assessed up to 2 years | Will be estimated using the Kaplan-Meier method. |
| Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events | Up to 2 years | 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. |
| Manufacturing success rate and successful manufacture of > 5 doses and administration of 1 or more doses of AGS-003-BLD | Up 2 years | Descriptive statistics (frequency table) and histogram will be used to summarize the success rate. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in CD28 + T cell level with pathological complete response | Baseline up to 2 years | Descriptive statistics (mean, sd, median, iqr) and longitudinal plots (raw value, change, and change in percentage) will be used to summarize the correlative endpoints. Further analysis will depend on the amount of data received and will be mainly exploratory. |
| Change in frequency of CD11a high PD-1+ CD8+ T cells (and their expression of Bim) in peripheral blood | Baseline up to 2 years | Descriptive statistics (mean, sd, median, iqr) and longitudinal plots (raw value, change, and change in percentage) will be used to summarize the correlative endpoints. Further analysis will depend on the amount of data received and will be mainly exploratory. |
Countries
United States
Outcome results
None listed