Neoadjuvant Gemcitabine, Cisplatin, Plus Nivolumab in Patients With Muscle-invasive Bladder Cancer With Selective Bladder Sparing
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab
- Conditions
- Bladder Cancer
- Sponsor
- Matthew Galsky
- Enrollment
- 76
- Locations
- 7
- Primary Endpoint
- Clinical Complete Response (CCR) Rate
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Matthew Galsky
Sponsor-Investigator
Hoosier Cancer Research Network
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
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
Arms & Interventions
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.
Intervention: Nivolumab
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.
Intervention: Gemcitabine
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.
Intervention: Cisplatin
Outcomes
Primary Outcomes
Clinical Complete Response (CCR) Rate
Time Frame: 24 months
Clinical complete response rate will be defined as the percentage of patients who achieved cT0 or cTa disease after gemcitabine, cisplatin, plus nivolumab.
Predict Benefit From Treatment
Time Frame: 24 months
Determine the ability of clinical complete response (cT0 or cTa) to predict benefit from treatment.Benefit will be defined as a pathologic complete response (\<pT1) in patients undergoing cystectomy and 2 year metastasis-free in patients pursuing surveillance. The positive predictive value of CCR with 95% confidence interval are presented in Outcome Measure Data Table. Positive predictive value is the ratio of patients truly diagnosed as positive to all those who had positive test results.
Secondary Outcomes
- Pathologic Complete Response Rate in Patients Undergoing Cystectomy(Up to a maximum of 53 months)
- Recurrence-free Survival(Up to a maximum of 60 months)
- Association Between a Prespecified Panel of Genomic Biomarkers and Benefit From Treatment in Patients Achieving a Clinical Complete Response.(24 months)
- Adverse Events(AE had been recorded from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 13 months.)
- Bladder Intact Overall Survival(Up to a maximum of 60 months)
- Overall Survival(Up to a maximum of 60 months)