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

NCT03558087 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HCRN GU16-257
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 7

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

Keywords

muscle-invasive

Outcome Measures

Primary Outcomes (2)

• Clinical Complete Response (CCR) Rate

  Clinical complete response rate will be defined as the percentage of patients who achieved cT0 or cTa disease after gemcitabine, cisplatin, plus nivolumab.

  24 months

• Predict Benefit From Treatment

  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.

  24 months

Secondary Outcomes (6)

• 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

• Recurrence-free Survival

  Up to a maximum of 60 months

• Pathologic Complete Response Rate in Patients Undergoing Cystectomy

  Up to a maximum of 53 months

• Association Between a Prespecified Panel of Genomic Biomarkers and Benefit From Treatment in Patients Achieving a Clinical Complete Response.

  24 months

Study Arms (1)

Gemcitabine, Cisplatin and Nivolumab

EXPERIMENTAL

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.

Drug: Nivolumab; Drug: Gemcitabine; Drug: Cisplatin

Interventions

Nivolumab 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).

Also known as: Opdivo

Gemcitabine, Cisplatin and Nivolumab

Gemcitabine DRUG

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

Also known as: Gemzar

Gemcitabine, Cisplatin and Nivolumab

Cisplatin DRUG

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

Also known as: Platinol

Gemcitabine, Cisplatin and Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Matthew Galsky: lead
• Bristol-Myers Squibb: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (7)

City of Hope

Duarte, California, 91010, United States

Location

Univerity of Southern California

Los Angeles, California, 90033, United States

Location

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

New York, New York, 10029, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Penn Medicine Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Huntsman Cancer Institute University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Nivolumab; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

317-921-2050

Study Officials

• Matthew Galsky, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: June 5, 2018
• First Posted: June 15, 2018
• Study Start: July 13, 2018
• Primary Completion: February 16, 2024
• Study Completion: March 7, 2024
• Last Updated: June 27, 2024
• Results First Posted: June 27, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)