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

NCT02944357 | Withdrawn DMC

• 3 other identifiers: MC1452NCI-2016-01517P30CA015083
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  Treatment visit 20 (Cycle 8) - After the 8th dose (3rd adjuvant) of AGS-003 - Bladder therapy, up to 12 weeks

Secondary Outcomes (8)

• 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

• Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events

  Up to 2 years

Other Outcomes (2)

• Change in CD28 + T cell level with pathological complete response

  Baseline up to 2 years

• Change in frequency of CD11a high PD-1+ CD8+ T cells (and their expression of Bim) in peripheral blood

  Baseline up to 2 years

Study Arms (1)

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

EXPERIMENTAL

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.

Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Procedure: Radical Cystectomy; Biological: Tumor Cell-Derived Vaccine Therapy

Interventions

Cisplatin DRUG

Given IV

Also known as: 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

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

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011, LY188011

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

Radical Cystectomy PROCEDURE

Undergo cystectomy

Also known as: Complete Cystectomy

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

Tumor Cell-Derived Vaccine Therapy BIOLOGICAL

Given AGS-003-BLD ID

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Interventions

Cisplatin; transplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Gemcitabine; Cystectomy

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Brian Costello

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2016
• First Posted: October 25, 2016
• Study Start: November 1, 2016
• Primary Completion: September 5, 2017
• Study Completion: September 5, 2017
• Last Updated: November 17, 2017

Record last verified: 2016-10

Locations

US (1)