Clinical Trials /

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

NCT03558087

Description:

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.

Related Conditions:
  • Bladder Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Gemcitabine, Cisplatin, Plus Nivolumab in Patients With Muscle-invasive Bladder Cancer With Selective Bladder Sparing
  • Official Title: Neoadjuvant Gemcitabine, Cisplatin, Plus Nivolumab in Patients With Muscle-invasive Bladder Cancer With Selective Bladder Sparing

Clinical Trial IDs

  • ORG STUDY ID: HCRN GU16-257
  • NCT ID: NCT03558087

Conditions

  • Bladder Cancer

Interventions

DrugSynonymsArms
NivolumabOpdivoGemcitabine, Cisplatin and Nivolumab
GemcitabineGemzarGemcitabine, Cisplatin and Nivolumab
CisplatinPlatinolGemcitabine, Cisplatin and Nivolumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Gemcitabine, Cisplatin and NivolumabExperimentalCombination 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.
  • Nivolumab
  • Gemcitabine
  • Cisplatin

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the clinical complete response rate (cT0 or cTa) with gemcitabine, cisplatin, plus nivolumab
Time Frame:24 months
Safety Issue:
Description:Clinical complete response rate will be defined as cT0 or cTa disease after gemcitabine, cisplatin, plus nivolumab.

Secondary Outcome Measures

Measure:Assess Adverse Events
Time Frame:24 months
Safety Issue:
Description:Assess adverse events according to the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4
Measure:Bladder intact overall survival
Time Frame:24 Months
Safety Issue:
Description:Bladder-intact overall survival is defined as the time from initiation of treatment until death or cystectomy
Measure:Recurrence-free survival
Time Frame:24 months
Safety Issue:
Description:Recurrence-free survival is defined as the time from initiation of treatment to death or recurrence, depending on which occurs first
Measure:Pathologic complete response rate in patients undergoing cystectomy
Time Frame:24 Months
Safety Issue:
Description:Pathologic complete response rate in patients undergoing radical cystectomy is defined as the proportion of patients with <pT1
Measure: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
Safety Issue:
Description:Benefit will be defined as a pathologic complete response (p<T1) in patients undergoing cystectomy and 2 years metastasis-free in patients pursuing surveillance

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Matthew Galsky

Trial Keywords

  • muscle-invasive

Last Updated