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

NCT ID: NCT03558087

Last Updated: 2024-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-13
• Study Completion Date: 2024-03-07

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.

Conditions

Bladder Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

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).

Gemcitabine

Intervention Type: DRUG

Gemcitabine 1000mg/m\^2 will be administered on Days 1 and 8 for four 21-day cycles.

Cisplatin

Intervention Type: DRUG

Cisplatin 70mg\^m2 will be administered on Day 1 for four 21-day cycles.

Interventions

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).

Intervention Type: DRUG

Gemcitabine

Gemcitabine 1000mg/m\^2 will be administered on Days 1 and 8 for four 21-day cycles.

Intervention Type: DRUG

Cisplatin

Cisplatin 70mg\^m2 will be administered on Day 1 for four 21-day cycles.

Intervention Type: DRUG

Other Intervention Names

Opdivo; Gemzar; Platinol

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 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: collaborator

Matthew Galsky

OTHER

Sponsor Role: lead

Responsible Party

Matthew Galsky

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Matthew Galsky, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

City of Hope

Duarte, California, United States

Univerity of Southern California

Los Angeles, California, United States

Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center

New York, New York, United States

Oregon Health & Science University

Portland, Oregon, United States

Penn Medicine Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Huntsman Cancer Institute University of Utah

Salt Lake City, Utah, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HCRN GU16-257

Identifier Type: -

Identifier Source: org_study_id