A Study to Test the Safety of Immunotherapy With Nivolumab Alone or With Ipilimumab Before Surgery for Bladder Cancer Patients Who Are Not Suitable for Chemotherapy

NCT03520491 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 18-042
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to test if immunotherapy with nivolumab alone or in combination with ipilimumab is safe and does not delay the planned bladder cancer surgery. The investigators want to see if treatment with these drugs prior to surgery may decrease the size of the bladder cancer and thus could help make the surgery more successful.

Conditions

Bladder Cancer

Keywords

Immunotherapy; Nivolumab; Ipilimumab; 18-042

Outcome Measures

Primary Outcomes (1)

• number of patients who proceed to radical cystectomy and pelvic lymph node dissection (RC-PLND)

  within 60 days after completion of neoadjuvant nivolumab or nivolumab in combination with ipilimumab for cisplatin-ineligible MIBC, without delays due to treatment-related toxicities or progressive disease

Study Arms (4)

Cohort 1

EXPERIMENTAL

Nivolumab 3 mg/kg on day 1 of each cycle for a total of 5 cycles. Each cycle will be two weeks long and treatment will occur during weeks 0, 2, 4, 6, and 8.

Drug: Nivolumab; Procedure: Radical cystectomy

Cohort 2

EXPERIMENTAL

Ipilimumab 3 mg/kg and Nivolumab 1 mg/kg on day 1 of each cycle, followed by Nivolumab 3 mg/kg on day 22 of each cycle for a total of 2 cycles. Each cycle will be six weeks long. Ipilimumab and Nivolumab will occur on weeks 0 and 6 while Nivolumab alone will occur on weeks 3 and 9.

Drug: Nivolumab; Drug: Ipilimumab; Procedure: Radical cystectomy

Cohort 3

EXPERIMENTAL

Ipilimumab 3 mg/kg on day 1 each cycle and Nivolumab 1 mg/kg on day 1 of each cycle for a total of 3 cycles. Each cycle will be three weeks long and treatment will occur during weeks 0, 3, and 6.

Drug: Nivolumab; Drug: Ipilimumab; Procedure: Radical cystectomy

Cohort U (UTUC patients) is independent from Cohorts 1 - 3. ( who are cisplatin-ineligible)

EXPERIMENTAL

Ipilimumab 3 mg/kg and Nivolumab 1 mg/kg on day 1, of each cycle, followed by Nivolumab 3 mg/kg on day 22 and Ipilimumab 3mg/kg and Nivolumab 1mg/kg on day 45.

Drug: Nivolumab; Drug: Ipilimumab; Procedure: Radical cystectomy

Interventions

Nivolumab DRUG

Nivolumab 3 mg/kg or Nivolumab 1 mg/kg

Cohort 1; Cohort 2; Cohort 3; Cohort U (UTUC patients) is independent from Cohorts 1 - 3. ( who are cisplatin-ineligible)

Ipilimumab DRUG

Ipilimumab 3 mg/kg

Cohort 2; Cohort 3; Cohort U (UTUC patients) is independent from Cohorts 1 - 3. ( who are cisplatin-ineligible)

Radical cystectomy PROCEDURE

RC-PLND is to take place within 60 days from the last dose of treatment.(After week 10 for cohort 1, after week 11 for cohort 2, and after week 9 for cohort 3.)

Cohort 1; Cohort 2; Cohort 3; Cohort U (UTUC patients) is independent from Cohorts 1 - 3. ( who are cisplatin-ineligible)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of urothelial carcinoma of the bladder. Variant histology is acceptable if there is a predominant urothelial component.
• For MUSCLE-INVASIVE UROTHELIAL CANCER OF THE BLADDER (Cohorts 1 - 3):
• ° Cystoscopically and radiographically confirmed cT2-4a cN0 cM0 disease. Patients with cT4a disease invading into the prostatic stroma with no cystoscopic confirmation of muscle invasion are eligible.
• For UROTHELIAL CARCINOMA OF THE UPPER URINARY TRACT (URETER OR RENAL PELVIS) (Cohort U):
• °Histologically confirmed high grade urothelial carcinoma of the upper tract and/or radiographically visible tumor stage T2-T4a N0/x M0 disease with positive selective urinary cytology. Hydronephrosis associated with tumor on imaging or biopsy will be considered invasive by definition. (Variant histology is acceptable if there is a predominant urothelial component)
• Patients ineligible for cisplatin based on any of the following criteria:
• Estimated or calculated creatinine clearance ≥ 30ml/min but \< 60 ml/min
• Grade 2 or above audiometric hearing loss (per CTCAE v4.0)
• Grade 2 or above peripheral neuropathy (per CTCAE v4.0)
• Availability of tumor specimen block or 30 unstained slides from diagnosis of muscle-invasive disease. Patients with fewer than 30 slides available may be enrolled after discussion with the Principal Investigator.
• Karnofsky performance status ≥ 70%.
• Medically appropriate candidate for radical cystectomy, as per MSK Attending Urologic Oncologist
• Age ≥ 18 years.
• Required initial laboratory values:
• Absolute neutrophil count ≥ 1.5 x 10\^9/L

You may not qualify if:

• Prior treatment with systemic chemotherapy for urothelial cancer, including immune checkpoint inhibitors for non-muscle invasive bladder cancer. (Prior intravesical treatment such as BCG is allowed.)
• Presence of active autoimmune disease, symptoms, or conditions, with the following exceptions:
• °Subjects with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, asymptomatic laboratory evidence of autoimmune disease (e.g.: +ANA, +RF, anti-thyroglobulin antibodies), 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 equivalent) or other immunosuppressive medications within 14 days of first dose of study drug. Inhaled or topical steroids, and adrenal replacement steroid doses are permitted in the absence of active autoimmune disease.
• Unstable angina.
• New York Heart Association (NYHA) Grade II or greater congestive heart failure.
• History of myocardial infarction within 6 months.
• History of stroke within 6 months.
• Evidence of bleeding diathesis or coagulopathy. Therapeutic anticoagulation is permitted, but patients must be on a stable dose.
• Major surgical procedure within 28 days prior to the study. (Transurethral resection of bladder tumor is permitted
• Serious, non-healing wound, ulcer, or bone fracture.
• Other prior malignancy active within the previous 2 years except for local or organ-confined early stage cancer that has been definitively treated with curative intent or does not require treatment, does not require ongoing treatment, has no evidence of active disease, and has a negligible risk of recurrence and is therefore unlikely to interfere with the endpoints of the study.
• Subjects who have received prior therapy with any T cell co-stimulation or checkpoint pathways such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-CD137; or other medicines specifically targeting T cells are prohibited. Prior IL-2 is permitted.
• Prior therapy with intravesical BCG within 6 weeks of treatment.
• Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBV sAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (All protocol activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (All protocol activities)

Uniondale, New York, 11553, United States

Location

Related Publications (1)

• Giannakodimos I, Ziogou A, Giannakodimos A, Tzelepis K, Kratiras Z, Fragkiadis E, Zachos I, Tzortzis V, Chrisofos M, Charalampakis N. Neoadjuvant immunotherapy for muscle-invasive bladder cancer: a 2025 update. Immunotherapy. 2025 Apr;17(6):447-455. doi: 10.1080/1750743X.2025.2501929. Epub 2025 May 6.

  PMID: 40329651 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Nivolumab; Ipilimumab; Cystectomy

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; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Scott Niglio, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a pilot study designed to evaluate neoadjuvant nivolumab and nivolumab in combination with ipilimumab in patients with muscle-invasive bladder cancer (MIBC) or urothelial cancers of the upper urinary tract (ureter or renal pelvis) \[UTUC\], who are ineligible for treatment with cisplatin-based chemotherapy. The study is designed with three sequential 15-patient cohorts.

Study Record Dates

• First Submitted: April 26, 2018
• First Posted: May 9, 2018
• Study Start: April 25, 2018
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (7)