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Trial record 5 of 467 for:    nivolumab

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

This study is not yet open for participant recruitment.
See Contacts and Locations
Verified August 2016 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT02845323
First received: July 13, 2016
Last updated: August 2, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Urothelial Carcinoma Bladder Cancer Drug: Nivolumab in combination with Urelumab Drug: Nivolumab monotherapy Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Study of Neoadjuvant Nivolumab With and Without Urelumab in Patients With Cisplatin-Ineligible Muscle-Invasive Urothelial Carcinoma of the Bladder

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • To evaluate the number of participants with treatment-related adverse events as assessed by CTCAE v 4.0 [ Time Frame: 2 years ]
  • Proportion of patients achieving pathologic response (<pT2N0) with Nivolumab and Urelumab and the use of Urelumab alone [ Time Frame: 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 [ Time Frame: 2 years ]
  • Change in expression for pathologic tumor response as defined by cystectomy pathologic staging <pT2 N0 in patients treated with Nivolumab [ Time Frame: 2 years ]
  • Prognostic value of tumor bx 4-1BB (CD137)& 4-1BB ligand (CD137L) expression [ Time Frame: 2 years ]
  • Change in expression, assessed by (IHC) analysis, for tumor response, defined by cystectomy staging < pT2N0, in cisplatin-ineligible MIBC pts tx w/Urelumab. [ Time Frame: 2 years ]
  • Prognostic value of tumor biopsy 4-1BB expression [ Time Frame: 2 years ]
  • Change in expression, assessed by (IHC) analysis, for pathologic CR response, defined by cystectomy staging pT0N0, in cisplatin-ineligible MIBC pts tx w/ Urelumab. [ Time Frame: 2 years ]
  • Proportion of patients achieving pathologic complete response with neoadjuvant Nivolumab and Urelumab (Arm A) and Nivolumab monotherapy (Arm B). [ Time Frame: 2 years ]

Estimated Enrollment: 44
Study Start Date: September 2016
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nivolumab in combination with Urelumab

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
Two cycles of Nivolumab Two cycles of Urelumab
Other Name: Opdivo
Active Comparator: Nivolumab monotherapy
Nivolumab 240 mg will be administered by 1 hour intravenous infusion on day 1 and day 15 for two cycles
Drug: Nivolumab monotherapy
Two cycles of Nivolumab alone

Detailed Description:

This is phase II clinical trial design randomizing patients with cisplatin-ineligible MIBC (stages T2-T4, N0-1, 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, but are fit to undergo surgical resection of their cancer by cystectomy. Patients with resectable clinical node positive disease within the true pelvis (N1) are eligible.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  • 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:

    1. 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)

iv.Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s)

b) Cirrhosis, chronic active hepatitis or chronic persistent hepatitis

c) Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)

d) 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.

e) 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02845323

Contacts
Contact: Noah Hahn, MD 443-287-2886 nhahn4@jhmi.edu
Contact: Rana Sullivan, RN 410-614-6337 tomalra@jhmi.edu

Locations
United States, Maryland
Johns Hopkins Hospital Not yet recruiting
Baltimore, Maryland, United States, 21205
Contact: Noah Hahn, MD    443-287-2886    nhahn4@jhmi.edu   
Contact: Rana Sullivan, RN    410-614-6337    tomalra@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Noah Hahn, MD Johns Hopkins University
  More Information

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02845323     History of Changes
Other Study ID Numbers: J1682
IRB00103062 ( Other Identifier: JHMIRB )
Study First Received: July 13, 2016
Last Updated: August 2, 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Nivolumab
Carcinoma
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Cisplatin
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 26, 2017