Neoadjuvant Nivolumab With and Without Urelumab in Cisplatin-Ineligible or Chemotherapy-refusing Patients With Muscle-Invasive Urothelial Carcinoma of the Bladder

NCT02845323 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: J1682IRB00103062
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 5

Brief Summary

This study evaluates the post cystectomy CD8+ tumor response of patients receiving Nivolumab plus Urelumab versus Nivolumab alone. Half the patients will receive Nivolumab plus Urelumab, while the other half will receive Nivolumab alone.

Conditions

Urothelial Carcinoma; Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Immune response to treatment with Nivolumab and Urelumab compared to Nivolumab monotherapy measured by tumor infiltrating CD8+ T cell density at cystectomy

  2 years

Secondary Outcomes (9)

• To evaluate the number of participants with treatment-related adverse events as assessed by CTCAE v 4.0

  2 years

• Proportion of patients achieving pathologic response (<pT2N0) with Nivolumab and Urelumab and the use of Urelumab alone

  2 years

• Prognostic value of tumor biopsy PD-1 and PD-L1 expression and change in expression for pathologic tumor response as defined by cystectomy pathologic staging <pT2 N0 in patients treated with Nivolumab

  2 years

• Change in expression for pathologic tumor response as defined by cystectomy pathologic staging <pT2 N0 in patients treated with Nivolumab

  2 years

• Prognostic value of tumor bx 4-1BB (CD137)& 4-1BB ligand (CD137L) expression

  2 years

Study Arms (2)

Nivolumab in combination with Urelumab

EXPERIMENTAL

Nivolumab and Urelumab combination: Nivolumab 240 mg will be administered by 1 hour intravenous infusion on day 1 and day 15 for two cycles Urelumab 8mg will be administered by 1 hour intravenous infusion on day 1 for two cycles

Drug: Nivolumab in combination with Urelumab

Nivolumab monotherapy

ACTIVE COMPARATOR

Nivolumab 240 mg will be administered by 1 hour intravenous infusion on day 1 and day 15 for two cycles

Drug: Nivolumab monotherapy

Interventions

Nivolumab in combination with Urelumab DRUG

Two cycles of Nivolumab Two cycles of Urelumab

Also known as: Opdivo

Nivolumab in combination with Urelumab

Nivolumab monotherapy DRUG

Two cycles of Nivolumab alone

Nivolumab monotherapy

Eligibility Criteria

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

You may qualify if:

• Electively refusing cisplatin-based neoadjuvant chemotherapy or
• Ineligible to receive cisplatin-based neoadjuvant chemotherapy based upon at least one of the following criteria:
• Creatinine clearance \< 60 ml/min
• ECOG status =2
• Grade \> 2 hearing loss
• Grade \> 2 neuropathy
• New York Heart Association Class III heart failure
• Age ≥ 18 years old at time of consent
• Patients must have the following laboratory values:
• a) Absolute neutrophil count (ANC) ≥ 1.5 K/mm3 (must be stable off any growth factor within 4 weeks of first study drug administration) b) Platelets ≥ 100 K/mm3 (transfusion to achieve this level is not permitted within 2 weeks of first study drug administration) c) Hemoglobin (Hgb) ≥ 9 g/dL d) Serum total bilirubin: ≤ 1.5 x ULN e) ALT and AST ≤ 3.0 x ULN f) Serum creatinine clearance (CrCl) ≥ 30 mL/min using the Cockcroft-Gault equation, see formula below:
• CrCl = \[140-age (years)\] x weight (kg) / \[72 x serum Cr (mg/dL)\] (if patient is female multiply the above by 0.85)
• Patients who give a written informed consent obtained according to local guidelines

You may not qualify if:

• Patients with locally advanced unresectable or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 28 days prior to study registration. The required radiographic imaging includes:
• a) Abdomen/Pelvis - CT scan b) Chest - chest x-ray or CT scan
• Patients with concurrent upper urinary tract (i.e. ureter, renal pelvis) invasive urothelial carcinoma.
• Patients with another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer
• Patients who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
• Patients who have received prior therapy with immune checkpoint inhibitors (e.g. anti-PD-1, anti-PD-L1, anti-LAG3, anti-CTLA-4) or immune costimulatory molecules (e.g. anti-CD137, anti-OX40, anti-GITR) directed agents.
• Patients who have had radiotherapy ≤ 4 weeks prior to starting study drug, or who have not recovered from radiotherapy toxicities
• Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures (i.e. TURBT), percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
• Patients with history of alcoholic or non-alcoholic steatohepatitis (NASH), auto-immune hepatitis, or previous grade 3-4 drug-related hepatitis. (Note: Patients with radiographic evidence of steatohepatitis are excluded unless a liver biopsy is obtained demonstrating no evidence of alcoholic or non-alcoholic steatohepatitis).
• Patient with history of prior solid organ or allogeneic bone marrow transplant.
• Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
• Clinically significant cardiac diseases, including any of the following:
• i. History or presence of serious uncontrolled ventricular arrhythmias
• ii.Clinically significant resting bradycardia
• iii.Any of the following within 3 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE)

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Bristol-Myers Squibb: collaborator

Study Sites (5)

UCLA Institute of Urologic Oncology

Los Angeles, California, 90095, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms

Interventions

Nivolumab; urelumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; 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

Study Officials

• Noah Hahn, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 13, 2016
• First Posted: July 27, 2016
• Study Start: May 16, 2017
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)