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Trial record 1 of 1 for:    Nivolumab in Treatment of Bladder Cancer (MIBC) Undergoing Cystectomy
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Nivolumab and Gemcitabine in Treatment of Bladder Cancer (MIBC) Undergoing Cystectomy

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ClinicalTrials.gov Identifier: NCT03294304
Recruitment Status : Not yet recruiting
First Posted : September 27, 2017
Last Update Posted : December 29, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:
This is a multi-center Phase II study to determine the safety and efficacy of nivolumab when given in combination with cisplatin and gemcitabine as neoadjuvant treatment in patients with muscle-invasive bladder cancer (MIBC) prior to standard of care radical cystectomy. Patients will receive neoadjuvant treatment with nivolumab in combination with gemcitabine-cisplatin (GC) every 3 weeks for 4 treatment cycles over 12 weeks followed by standard of care radical cystectomy.

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

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 41 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Neoadjuvant Nivolumab With Cisplatin and Gemcitabine in Muscle-Invasive Bladder Cancer (MIBC) Patients Undergoing Radical Cystectomy
Anticipated Study Start Date : January 21, 2018
Estimated Primary Completion Date : November 1, 2019
Estimated Study Completion Date : November 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Nivolumab, Cisplatin, & Gemcitabine Drug: Nivolumab
Nivolumab will be given at a fixed dose of 360 mg IV on Day 8 every 21 days for 4 cycles.
Other Name: Opdivo
Drug: Cisplatin
Cisplatin will be given at 70 mg/m2 IV on Day 1 every 21 days, and if using split-dose cisplatin (for creatinine clearance <50 ml/min), cisplatin will be given at 35 mg/m2 IV Day 1 and Day 8 every 21 days for 4 cycles.
Other Name: Platinol
Drug: Gemcitabine
Gemcitabine will be given at 1000 mg/m2 IV on days 1, 8 every 21 days for 4 cycles.
Other Name: Gemzar

Outcome Measures

Primary Outcome Measures :
  1. Pathologic Response Rate (PaR) at time of radical cystectomy. PaR is defined as absence of residual MIBC at cystectomy in the surgical specimen (pathologic down-staging to ≤pT1pN0, which includes pT0, pT1,pTa and pTis) [ Time Frame: Surgery Day 1 ]
    Incidence of Measurable Disease

Secondary Outcome Measures :
  1. Safety of Nivolumab and Gemcitabine [ Time Frame: Cycle 1 Day 1 ]
    Incidence of Adverse Events

  2. Safety of Nivolumab and Gemcitabine [ Time Frame: Cycle 1 Day 8 ]
    Incidence of Adverse Events

  3. Safety of Nivolumab and Gemcitabine [ Time Frame: Cycle 2 Day 1 ]
    Incidence of Adverse Events

  4. Safety of Nivolumab and Gemcitabine [ Time Frame: Cycle 2 Day 8 ]
    Incidence of Adverse Events

  5. Safety of Nivolumab and Gemcitabine [ Time Frame: Cycle 3 Day 1 ]
    Incidence of Adverse Events

  6. Safety of Nivolumab and Gemcitabine [ Time Frame: Cycle 3 Day 8 ]
    Incidence of Adverse Events

  7. Safety of Nivolumab and Gemcitabine [ Time Frame: Cycle 4 Day 1 ]
    Incidence of Adverse Events

  8. Safety of Nivolumab and Gemcitabine [ Time Frame: Cycle 4 Day 8 ]
    Incidence of Adverse Events

  9. Safety of Nivolumab and Gemcitabine [ Time Frame: 30 Days +/- 7 Days after last chemotherapy ]
    Incidence of Adverse Events

  10. Safety of Nivolumab and Gemcitabine [ Time Frame: 4 weeks post radical cyctectomy ]
    Incidence of Adverse Events

  11. Progression Free Survival (PFS) [ Time Frame: Every 3 Months for 2 Years ]
    Incidence of PFS

Eligibility Criteria

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

Inclusion Criteria:

  • Patients with MIBC (predominantly urothelial carcinoma) with clinical stage T2-T4a and N<1 disease (solitary lymph node measuring < 2 cm) and M0 and deemed eligible for radical cystectomy.
  • Age ≥ 18 years
  • ECOG Performance Status of 0 or 1.
  • Required initial laboratory values within 14 days of study registration:

    • Absolute Neutrophil Count ≥ 1000 cells/mm^3
    • Platelets ≥ 100,000 cells/mm^3
    • Hemoglobin > 9.0 g/dL
    • Bilirubin ≤ 1.5 times the upper limit of normal (ULN) for the institution (For patients with known Gilbert's disease: bilirubin ≤ 3 x ULN)
    • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN for the institution
    • Creatinine clearance ≥ 50 ml/min by Cockcroft-Gault formula or 24 hour urinary clearance (CrCl = [140-age (years)] x weight (kg) / [72 x serum Cr (mg/dL)] (if patient is female multiply the above by 0.85)
    • Alkaline phosphatase ≤ 2.5 x ULN for the institution
    • INR and aPTT ≤ 1.5 x ULN if not on therapeutic anticoagulation. Patients receiving therapeutic anticoagulation will be allowed if maintained on a stable dose.
  • Females of childbearing potential and males who are not surgically sterile and with partners of childbearing potential must agree to use effective contraception during study treatment for 5 months for females and 7 months for males after the last dose of nivolumab.
  • Ability to provide a signed and dated consent or have a legally authorized representative to provide written and signed consent prior to the initiation of any research related procedures.
  • Patients must agree to submission of tumor blocks or 15-20 formalin-fixed paraffin embedded (FFPE) slides of 5-10 microns in thickness from TURBT and radical cystectomy tissues.

Exclusion Criteria:

  • Presence of N2-3 or M1 disease.
  • Ineligible to receive cisplatin by meeting one or more of the following criteria; creatinine clearance of < 50 mL/min, hearing loss of 25 dB at two contiguous frequencies, Grade 2 or higher peripheral neuropathy, New York Heart Association Class III or IV heart failure, ECOG performance status 2 or higher.
  • Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study.
  • Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (>New York Heart Association Class 2), stroke, serious cardiac arrhythmia.
  • Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness.
  • Pregnancy, lactation, or breast-feeding. Women of childbearing potential must have a negative urine pregnancy test at screening.
  • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, systemic vasculitis, or glomerulonephritis.
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan, history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Active hepatitis B virus (HBV, chronic or acute, defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C antibody. Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBc Ab] and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to Cycle 1, Day 1 and confirmed to be negative. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Active tuberculosis or BCG infection
  • Active infection requiring systemic antibiotics within 2 weeks prior to Cycle 1, Day 1. Prophylactic short-term antibiotics will be allowed.
  • Prior allogeneic stem cell or solid organ transplant.
  • Administration of intravesical bacillus Calmette-Guerin (BCG) within 4 weeks before Cycle 1, Day 1.
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study.
  • Persisting toxicity from prior therapy (NCI CTCAE v4.03 Grade >1); however alopecia and sensory neuropathy Grade <t2, or other Grade <2 AEs not constituting a safety risk, based on Investigator's judgement, are acceptable.
  • History of or active bone marrow disorders expected to interfere with study therapy (e.g. acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma).
  • Prior allogeneic stem cell or solid organ transplant.
  • Known primary central nervous system (CNS) malignancy.
  • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted but patients with psoriasis require a baseline ophthalmologic exam to rule out ocular manifestations. Rash must cover less than 10% of body surface area (BSA) and must be well controlled at baseline and only requiring topical steroids.
  • Any other chronic medical condition or psychiatric condition, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  • Malignancies other than the disease under study within 3 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or low-risk prostate cancer undergoing active surveillance. Patients on androgen deprivation therapy as part of adjuvant therapy after radiation for prostate cancer will be allowed.
  • Prior treatment with anti-PD-1, and CTLA-4, or anti-a PD-L1 therapeutic antibody or pathway-targeting agents.
  • Treatment with systemic immunostimulatory agents (including but not limited to interferon [IFN]-a or interleukin [IL]-2) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1
  • Concomitant use of systemic corticosteroids at physiologic doses or <10 mg/day of prednisone or equivalent.
  • Concomitant use of another investigational agent and/or treatment with an investigational agent within 4 weeks prior to Cycle 1, Day 1 (or within five halflives of the investigational product, whichever is longer).
  • Use of bisphosphonate therapy for osteoporosis will be allowed if started prior to study enrollment.
Contacts and Locations

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): NCT03294304

Contact: Shilpa Gupta, MD (612)-624-5620 guptash@umn.edu

Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Bristol-Myers Squibb
Principal Investigator: Shilpa Gupta, MD Masonic Cancer Center, University of Minnesota
More Information

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT03294304     History of Changes
Other Study ID Numbers: 2017LS039
First Posted: September 27, 2017    Key Record Dates
Last Update Posted: December 29, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Masonic Cancer Center, University of Minnesota:
Bladder Cancer

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