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

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

INTRODUCTION

  • Org Study ID: HCRN GU16-257
  • Secondary ID: N/A
  • NTC ID: NCT03558087
  • Sponsor: Matthew Galsky

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.

  • Overall Status
    Active, not recruiting
  • Start Date
    July 13, 2018
  • Phase
    Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Determine the clinical complete response rate (cT0 or cTa) with gemcitabine, cisplatin, plus nivolumab

Primary Outcome 1 - Timeframe: 24 months

Primary Outcome 2 - Measure: Determine the ability of clinical complete response (cT0 or cTa) to predict benefit from treatment.

Primary Outcome 2 - Timeframe: 24 months

CONDITION

  • Bladder Cancer

ELIGIBILITY

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 activity or to use 2 forms of effective methods of contraception from the time of informed consent to 5 months after the last dose of investigational product.. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method. Men will not be required to use contraception.
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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Matthew Galsky, MD

Role: Principal Investigator

Affiliation: Icahn School of Medicine at Mount Sinai

Overall Contact

Name: Matthew Galsky, MD

Phone: N/A

Email: N/A

LOCATION

Facility Status Contact