Pilot Study of Gemcitabine and Cisplatin Plus AGS-003-BLD in Patients With Muscle-Invasive Bladder Cancer Undergoing Neoadjuvant Cisplatin-Based Chemotherapy
Pilot Study of Gemcitabine and Cisplatin Plus AGS-003-BLD in Patients With Muscle-Invasive Bladder Cancer Undergoing Neoadjuvant Cisplatin-Based Chemotherapy
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.
Inclusion Criteria:
Exclusion Criteria:
RE-REGISTRATION EXCLUSION CRITERIA
Requirement for systemic chronic immunosuppressive drugs or systemic chronic corticosteroids for active autoimmune disorder(s) or other conditions (e.g.: rheumatoid arthritis, systemic lupus erythematous, multiple sclerosis, organ transplant recipient, etc.)
Known inability to undergo neoadjuvant gemcitabine and cisplatin combination treatment due to pre-existing medical conditions in the opinion of the treating physician or investigator
Immunotherapy =< 28 days prior to pre-registration (e.g. intravesical Bacillus Calmette-Guerin [BCG])
Any of the following prior therapies:
REGISTRATION EXCLUSION CRITERIA
Lymph node positive urothelial carcinoma
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements in the opinion of the investigator
Treatment with oral/systemic corticosteroids =< 14 days prior to registration, with the exception of topical or inhaled steroids or steroids given for the purpose of antiemetics during chemotherapy
New York Heart Association classification III or IV congestive heart failure
Central nervous system (CNS) metastases or seizure disorder
Any of the following:
Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) with the exception of intravesical therapy at the time of TURBT
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Clinically significant infections including human immunodeficiency virus (HIV), syphilis, and active hepatitis B or C
Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
Prior history of malignancy =< 3 years prior to registration, except for adequately treated non-melanoma skin cancer, adequately treated early stage breast cancer, adequately treated cervical cancer and non-metastatic prostate cancer under clinical control as deemed by treating physician or investigator
History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
History of major surgery or traumatic injury =< 28 days prior to registration or other major anticipated procedures requiring general anesthesia during study participation