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Urothelial CarcinomaPhase 2NCT02845323

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

A Phase 2 study testing Nivolumab in combination with Urelumab and Nivolumab monotherapy in people with Urothelial Carcinoma and Bladder Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 5 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urothelial Carcinoma, Bladder Cancer
What is being tested?
Nivolumab in combination with Urelumab and Nivolumab monotherapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
5 sitesUnited States
Study dates
16 May 2017to Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • New York Heart Association Class III heart failure
  • Age ≥ 18 years old at time of consent
  • Patients must have the following laboratory values:
  • 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

Who cannot join

  • 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:
  • 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.
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  • 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:
  • 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)
  • iv.Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s)
  • Cirrhosis, chronic active hepatitis or chronic persistent hepatitis
  • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
  • Known diagnosis of any condition (i.e. post-hematopoietic or organ transplant, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, etc.) that requires chronic immunosuppressive therapy. Usage of non-steroidal anti-inflammatory medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of gout are permitted. For questions, please consult the study chair.
  • Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
  • Pregnant or breast-feeding women
  • Women of child-bearing potential, who are biologically able to conceive, and not employing two forms of highly effective contraception. Highly effective contraception must be used throughout the trial and up to 8 weeks after the last dose of study drug (e.g. male condom with spermicidal; diaphragm with spermicide; intra-uterine device). Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 14 days prior to starting study drug
  • Fertile males not willing to use contraception, as stated above
  • Patients unwilling or unable to comply with the protocol

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

  • Johns Hopkins Hospital

    Baltimore, Maryland, 21205

  • University of Chicago

    Chicago, Illinois, 60637

  • UCLA Institute of Urologic Oncology

    Los Angeles, California, 90095

  • Columbia University Medical Center

    New York, New York, 10032

Other trials in United States

About this study

Official title: Randomized Phase II Study of Neoadjuvant Nivolumab With and Without Urelumab in Cisplatin-Ineligible or Chemotherapy-refusing Patients With Muscle-Invasive Urothelial Carcinoma of the Bladder

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.

Read the detailed description

This is phase II clinical trial design randomizing patients who are cisplatin-ineligible or chemotherapy-refusing with MIBC (stages T2-T4, N0-N2, M0) to one of two treatment arms: Arm A - Nivolumab in combination with Urelumab or Arm B - Nivolumab monotherapy.

The study population will include male and female patients over the age of 18 with muscle invasive urothelial carcinoma of the bladder (MIBC) who are not suitable for cisplatin-based chemotherapy or refuse chemotherapy, but are fit to undergo surgical resection of their cancer by cystectomy. Patients with resectable clinical node positive disease within the true pelvis are eligible.

Being tested
Nivolumab in combination with Urelumab, Nivolumab monotherapy
Medical subject headings
Carcinoma, Transitional Cell, Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nivolumab in combination with UrelumabDrug

    Also called Opdivo

    Two cycles of Nivolumab Two cycles of Urelumab

  • Nivolumab monotherapyDrug

    Two cycles of Nivolumab alone

Study groups in NCT02845323
Study groupRoleWhat they receive
Nivolumab in combination with UrelumabExperimentalNivolumab 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
Receives: Drug: Nivolumab in combination with Urelumab
Nivolumab monotherapyActive comparatorNivolumab 240 mg will be administered by 1 hour intravenous infusion on day 1 and day 15 for two cycles
Receives: Drug: Nivolumab monotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 2 years

Secondary outcomes (9)

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

    Measured: 2 years

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

    Measured: 2 years

  3. 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

    Measured: 2 years

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

    Measured: 2 years

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

    Measured: 2 years

  6. Change in expression, assessed by (IHC) analysis, for tumor response, defined by cystectomy staging < pT2N0, in cisplatin-ineligible MIBC pts tx w/Urelumab.

    Measured: 2 years

  7. Prognostic value of tumor biopsy 4-1BB expression

    Measured: 2 years

  8. Change in expression, assessed by (IHC) analysis, for pathologic CR response, defined by cystectomy staging pT0N0, in cisplatin-ineligible MIBC pts tx w/ Urelumab.

    Measured: 2 years

  9. Proportion of patients achieving pathologic complete response with neoadjuvant Nivolumab and Urelumab (Arm A) and Nivolumab monotherapy (Arm B).

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jul 2016 (estimated)
  2. Study start16 May 2017
  3. Primary completion31 Jul 2027 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02845323
Sponsor's protocol ID
J1682
Other IDs
IRB00103062
Status last verified
Mar 2026
First submitted
13 Jul 2016
Last updated
6 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab in combination with Urelumab and Nivolumab monotherapy in people with Urothelial Carcinoma and Bladder Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 6 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Immune response to treatment with Nivolumab and Urelumab compared to Nivolumab monotherapy measured by tumor infiltrating CD8+ T cell density at cystectomy (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02845323.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2026.

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