Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03558087
Recruitment Status : Active, not recruiting
First Posted : June 15, 2018
Last Update Posted : July 11, 2022
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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 76 participants
Allocation: N/A
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 : March 2023
Estimated Study Completion Date : August 2024

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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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 identified at screening (i.e., at least 15 unstained slides or paraffin block). Subjects without available archival tissue must be discussed with the sponsor-investigator.
  • Women of childbearing potential must have a negative serum or urine pregnancy within 7 days prior to C1D1. NOTE: "Women of childbearing potential" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 62 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.

NOTE: Women of childbearing potential (WOCBP) receiving nivolumab must be willing to abstain from heterosexual intercourse or to use 2 forms of effective methods of contraception from the time of informed consent to 5 months after the last dose of nivolumab or for the timeframe outlined per package insert for chemotherapy. This timeframe also applies to breastfeeding. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method. Male subjects capable of fathering a child that are sexually active with partners of childbearing potential must be willing to abstain from heterosexual intercourse or to use 2 forms of effective methods of contraception from the time of informed consent to the timeframe outlined per package insert for chemotherapy. Contraception is not required for nivolumab. The timeframes described in the previous 2 sentences apply to sperm donation. Two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.

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


Locations
Layout table for location information
United States, California
City of Hope
Duarte, California, United States, 91010
Univerity of Southern California
Los Angeles, California, United States, 90033
United States, New York
Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center
New York, New York, United States, 10029
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Penn Medicine Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, Utah
Huntsman Cancer Institute University of Utah
Salt Lake City, Utah, United States, 84112
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
Matthew Galsky
Bristol-Myers Squibb
Icahn School of Medicine at Mount Sinai
Investigators
Layout table for investigator information
Principal Investigator: Matthew Galsky, MD Icahn School of Medicine at Mount Sinai
Layout table for additonal information
Responsible Party: Matthew Galsky, Sponsor-Investigator, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT03558087    
Other Study ID Numbers: HCRN GU16-257
First Posted: June 15, 2018    Key Record Dates
Last Update Posted: July 11, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
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:
Layout table for MeSH terms
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
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
Immune Checkpoint Inhibitors