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Gemcitabine, Cisplatin, Plus Nivolumab in Patients With Muscle-invasive Bladder Cancer With Selective Bladder Sparing

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ClinicalTrials.gov Identifier: NCT03558087
Recruitment Status : Recruiting
First Posted : June 15, 2018
Last Update Posted : August 14, 2019
Sponsor:
Collaborators:
Bristol-Myers Squibb
Icahn School of Medicine at Mount Sinai
Information provided by (Responsible Party):
Matthew Galsky, Hoosier Cancer Research Network

Brief Summary:
This is a phase 2 trial seeking to define the safety and activity of gemcitabine, cisplatin, plus nivolumab as neoadjuvant therapy in patients with muscle-invasive bladder cancer and to define the role of clinical complete response in predicting benefit in patients opting to avoid cystectomy.

Condition or disease Intervention/treatment Phase
Bladder Cancer Drug: Nivolumab Drug: Gemcitabine Drug: Cisplatin Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 63 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant Gemcitabine, Cisplatin, Plus Nivolumab in Patients With Muscle-invasive Bladder Cancer With Selective Bladder Sparing
Actual Study Start Date : July 13, 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Experimental: Gemcitabine, Cisplatin and Nivolumab
Combination Therapy: Nivolumab 360mg IV, Gemcitabine 100mg/m^2 IV ,Cisplatin 70mg/m^2 IV for four 21-day cycles. At restaging, subjects with cT0 or cTa status may undergo cystectomy or continue maintenance Nivolumab 240mg IV for up to 8 14-day cycles. Subjects with > cTa status will undergo cystectomy.
Drug: Nivolumab
Nivolumab 360mg will be administered on Day 1 of each 21 day cycle for four 21-day cycles. Based on response and a balanced patient-physician discussion, subjects may receive nivolumab 240 mg for 8 cycles (cycle = 14 days).
Other Name: Opdivo

Drug: Gemcitabine
Gemcitabine 1000mg/m^2 will be administered on Days 1 and 8 for four 21-day cycles.
Other Name: Gemzar

Drug: Cisplatin
Cisplatin 70mg^m2 will be administered on Day 1 for four 21-day cycles.
Other Name: Platinol




Primary Outcome Measures :
  1. Determine the clinical complete response rate (cT0 or cTa) with gemcitabine, cisplatin, plus nivolumab [ Time Frame: 24 months ]
    Clinical complete response rate will be defined as cT0 or cTa disease after gemcitabine, cisplatin, plus nivolumab.

  2. Determine the ability of clinical complete response (cT0 or cTa) to predict benefit from treatment. [ Time Frame: 24 months ]
    Benefit will be defined as a pathologic complete response (<pT1) in patients undergoing cystectomy and 2 year metastasis-free in patients pursuing surveillance


Secondary Outcome Measures :
  1. Assess Adverse Events [ Time Frame: 24 months ]
    Assess adverse events according to the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4

  2. Bladder intact overall survival [ Time Frame: 24 Months ]
    Bladder-intact overall survival is defined as the time from initiation of treatment until death or cystectomy

  3. Recurrence-free survival [ Time Frame: 24 months ]
    Recurrence-free survival is defined as the time from initiation of treatment to death or recurrence, depending on which occurs first

  4. Pathologic complete response rate in patients undergoing cystectomy [ Time Frame: 24 Months ]
    Pathologic complete response rate in patients undergoing radical cystectomy is defined as the proportion of patients with <pT1

  5. Determine the association between a prespecified panel of genomic biomarkers and benefit from treatment in patients achieving a clinical complete response. [ Time Frame: 24 months ]
    Benefit will be defined as a pathologic complete response (p<T1) in patients undergoing cystectomy and 2 years metastasis-free in patients pursuing surveillance



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ECOG Performance Status of ≤ 1 within 28 days prior to registration.
  • Histological evidence of clinically localized muscle-invasive urothelial cancer of the bladder (i.e., ct2-4n0m0). candidate for cystectomy as per treating physician.
  • Demonstrate adequate organ function per listed criteria:
  • Absolute Neutrophil Count (ANC): ≥ 1.5 x 10^9/L
  • Hemoglobin (Hgb): ≥ 9 g/dL
  • Platelets: ≥ 100 x 10^9/L
  • Calculated creatinine clearance: Creatinine ≤ 1.5 or creatinine clearance ≥ 60 mL/min
  • Bilirubin: ≤ 1.5 × upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Aspartate aminotransferase (AST) : ≤ 3 × ULN
  • Alanine aminotransferase (ALT) : ≤ 3 × ULN
  • All subjects must have adequate archival tissue submitted prior to registration (i.e., at least 15 unstained slides or paraffin block).
  • Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception.
  • Women of childbearing potential must have a negative serum or urine pregnancy within 7 days prior to C1D1.
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year.

Exclusion Criteria:

  • Prior treatment with systemic chemotherapy for muscle-invasive urothelial cancer of the bladder
  • Active infection requiring systemic therapy
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
  • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
  • Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
  • Grade ≥ 2 neuropathy (NCI CTCAE version 4).
  • Prior radiation therapy for bladder cancer
  • Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (RNA) or hepatitis C antibody (HCV antibody) indicating acute or chronic infection.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Solid organ or allogeneic stem cell transplant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03558087


Contacts
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Contact: Matthew Galsky, MD 212-659-5599 matthew.galsky@mssm.edu
Contact: Ahran Lee 317-634-5842 ext 41 alee@hoosiercancer.org

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Yale Kim    626-218-0710 ext 80710    yakim@coh.org   
Principal Investigator: Sumanta Pal, MD         
United States, New York
Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Matthew Galsky, M.D.    212-241-8214    matthew.galsky@mssm.edu   
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Renee Rother    503-494-8236    rother@ohsu.edu   
Principal Investigator: Jeremy Cetnar, MD         
United States, Pennsylvania
Penn Medicine Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Sheryl Foster    215-615-2220    Sheryl.Foster@uphs.upenn.edu   
Principal Investigator: Ronac Mamtani, MD         
Sponsors and Collaborators
Matthew Galsky
Bristol-Myers Squibb
Icahn School of Medicine at Mount Sinai
Investigators
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Principal Investigator: Matthew Galsky, MD Icahn School of Medicine at Mount Sinai

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Responsible Party: Matthew Galsky, Sponsor-Investigator, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT03558087     History of Changes
Other Study ID Numbers: HCRN GU16-257
First Posted: June 15, 2018    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Matthew Galsky, Hoosier Cancer Research Network:
muscle-invasive

Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Cisplatin
Gemcitabine
Nivolumab
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological