Gemcitabine Hydrochloride, Cisplatin, and AGS-003-BLD in Treating Patients With Muscle-Invasive Bladder Cancer Undergoing Surgery

NCT ID: NCT02944357

Last Updated: 2017-11-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

NA

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-30

Study Completion Date

2017-09-05

Brief Summary

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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

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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.

Conditions

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Infiltrating Bladder Urothelial Carcinoma Stage II Bladder Urothelial Carcinoma Stage III Bladder Urothelial Carcinoma Stage IV Bladder Urothelial Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (gemcitabine hydrochloride, cisplatin, AGS-003-BLD)

NEOADJUVANT PHASE: Patients receive gemcitabine hydrochloride IV on days 1 and 8, AGS-003-BLD 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.

Group Type EXPERIMENTAL

Cisplatin

Intervention Type DRUG

Given IV

Gemcitabine Hydrochloride

Intervention Type DRUG

Given IV

Radical Cystectomy

Intervention Type PROCEDURE

Undergo cystectomy

Tumor Cell-Derived Vaccine Therapy

Intervention Type BIOLOGICAL

Given AGS-003-BLD ID

Interventions

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Cisplatin

Given IV

Intervention Type DRUG

Gemcitabine Hydrochloride

Given IV

Intervention Type DRUG

Radical Cystectomy

Undergo cystectomy

Intervention Type PROCEDURE

Tumor Cell-Derived Vaccine Therapy

Given AGS-003-BLD ID

Intervention Type BIOLOGICAL

Other Intervention Names

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Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum Cis-dichloroamine Platinum (II) Cis-platinous Diamine Dichloride Cis-platinum Cis-platinum II Cis-platinum II Diamine Dichloride Cismaplat Cisplatina Cisplatinum Cisplatyl Citoplatino Citosin Cysplatyna DDP (diamminedichloroplatinum) Lederplatin Metaplatin Neoplatin Peyrone's Chloride Peyrone's Salt Placis Plastistil Platamine Platiblastin Platiblastin-S Platinex Platinol Platinol- AQ Platinol-AQ Platinol-AQ VHA Plus Platinoxan Platinum Platinum Diamminodichloride Platiran Platistin Platosin dFdCyd Difluorodeoxycytidine Hydrochloride Gemzar LY-188011 LY188011 Complete Cystectomy

Eligibility Criteria

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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

* 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:

* Systemic chemotherapy for bladder cancer at any time; NOTE: intravesical chemotherapy is allowed
* Systemic chemotherapy for other malignancies =\< 3 years prior to pre-registration
* 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:

* Pregnant women
* Nursing women
* Men or women of childbearing potential who are unwilling to employ adequate contraception
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Brian Costello

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic

Rochester, Minnesota, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2016-01517

Identifier Type: REGISTRY

Identifier Source: secondary_id

MC1452

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MC1452

Identifier Type: -

Identifier Source: org_study_id