First-Line Gemcitabine, Cisplatin + Ipilimumab for Metastatic Urothelial Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Hoosier Cancer Research Network
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT01524991
First received: January 30, 2012
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

Gemcitabine plus cisplatin is standard treatment for advanced urothelial cancer. Ipilimumab has shown intriguing activity as neoadjuvant therapy in patients with clinically localized bladder cancer undergoing radical cystectomy. The combination of gemcitabine, cisplatin, plus ipilimumab may build on the chemosensitivity of urothelial carcinoma to produce more durable responses and improved outcomes.


Condition Intervention Phase
Urothelial Carcinoma
Drug: Gemcitabine
Drug: Cisplatin
Drug: Ipilimumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Gemcitabine, Cisplatin, Plus Ipilimumab as First-line Treatment for Patients With Metastatic Urothelial Carcinoma: Hoosier Oncology Group GU10-148

Resource links provided by NLM:


Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • One-Year Overall Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To determine the 1-year overall survival of patients with advanced/metastatic urothelial cancer treated with gemcitabine, cisplatin, plus ipilimumab.


Secondary Outcome Measures:
  • Progression-Free Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To determine the progression-free survival (using irRC and RECIST v1.0) of patients with advanced/metastatic urothelial carcinoma treated with gemcitabine, cisplatin, and ipilimumab.

  • Best Overall Response Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To determine the best overall response rate to treatment with gemcitabine, cisplatin, plus ipilimumab

  • Number of Adverse Events Experienced by Patients [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To determine the safety of treatment with gemcitabine, cisplatin, plus ipilimumab.


Estimated Enrollment: 36
Study Start Date: January 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Gemcitabine 1000 mg/m2 Days 1 & 8 Cisplatin 70 mg/m2 Day 1 Ipilimumab 10 mg/kg Day 1 (start cycle 3)
Drug: Gemcitabine
Gemcitabine 1000 mg/m2 Days 1 & 8 (all cycles)
Drug: Cisplatin
Cisplatin 70 mg/m2 Day 1 (all cycles)
Drug: Ipilimumab
Ipilimumab 10 mg/kg Day 1 (start cycle 3)

Detailed Description:

OUTLINE: This is a multi-center study

Gemcitabine 1000 mg/m2 Days 1 & 8 Cisplatin 70 mg/m2 Day 1 Ipilimumab 10 mg/kg Day 1 (start cycle 3)

Treatment during the induction phase will be administered in six 21-day cycles. During cycles 1 and 2, gemcitabine plus cisplatin will be administered WITHOUT ipilimumab. During cycles 3-6, combination therapy with gemcitabine, cisplatin, plus ipilimumab will be administered. Patients without evidence of disease progression (by irRC) after completion cycle 6 will continue single-agent ipilimumab maintenance every 3 months.

Karnofsky performance status (KPS) ≥ 80% within 14 days prior to registration for protocol therapy.

Life Expectancy: Not Specified

Hematopoietic:

  • White blood cell count (WBC) ≥ 3.5K/mm3
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • Platelets ≥ 100K/mm3
  • Absolute neutrophil count (ANC) ≥ 1.5k/mm3

Hepatic:

  • Bilirubin ≤ 1.5 times x Upper Limit of Normal (ULN) (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
  • Aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN. NOTE: If the patient has liver metastases present, then ≤ 5 x ULN

Renal:

  • Calculated creatinine clearance of ≥ 55 cc/min using the Cockcroft-Gault formula

Cardiovascular: Not Specified

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histological or cytological proof of urothelial carcinoma of the urethra, bladder, ureters, or renal pelvis.
  • Advanced (clinical stage T4b, unresectable) or metastatic disease.
  • Prior radiation therapy is allowed to < 25% of the bone marrow.
  • Age > 18 years at the time of consent.
  • Written informed consent and HIPAA authorization for release of personal health information.
  • Females must not be pregnant or breastfeeding.
  • WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of ipilimumab.
  • Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study [and for up to 26 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized.
  • Prior Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis). Patients with other immune disorders should not be enrolled without discussion with the principal investigator.

Exclusion Criteria:

  • No active CNS metastases. Subjects with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis.
  • No prior malignancy is allowed except for cancers that have been definitively treated with a risk of recurrence of < 30% based on the treating oncologists assessment.
  • Patients may not have received prior systemic chemotherapy for metastatic/advanced urothelial carcinoma. Prior neoadjuvant/adjuvant therapy is permitted if completed ≥ 12 months prior to registration for protocol therapy. Prior intravesical therapy is permitted.
  • No treatment with any investigational agent within 30 days prior to registration for protocol therapy.
  • No underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
  • No non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab).
  • No history of prior treatment with ipilimumab or prior CD137 agonist or CTLA 4 inhibitor or agonist.
  • No known active or chronic infection with HIV, Hepatitis B, or Hepatitis C.
  • No clinically significant infections as judged by the treating investigator.
  • No chronic systemic corticosteroids (defined as the equivalent of prednisone ≥ 20 mg PO daily for > 6 months during the past year)
  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: NCT01524991

Contacts
Contact: Matthew Galsky, M.D. 212-241-6756 matthew.galsky@mssm.edu
Contact: Cynthia Burkhardt, R.N. 317-921-2050 cyburkha@iupui.edu

Locations
United States, California
City of Hope: Duarte Recruiting
Duarte, California, United States, 91010
Contact: Przemyslaw Twardowski, M.D.       ptwardowski@coh.org   
Contact: Dorie Cook    626.256.4673 ext 61578    dcook@coh.org   
United States, Indiana
IU Health Goshen Hospital Recruiting
Goshen, Indiana, United States, 46527
Contact: Alex Starodub, M.D.    574-535-2886    astarodub@iuhealth.org   
Contact: Rebecca Eickhoff, R.N.    574.364.2649      
Indiana University Melvin & Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Costantine Albany, M.D.    317-278-1711    calbany@iu.edu   
Contact: Kerry Bridges    317-274-2552    kdbridge@iupui.edu   
IU Health Central Indiana Cancer Centers Recruiting
Indianapolis, Indiana, United States, 46219
Contact: Hillary Wu, M.D.    317-964-5253    hwu@iuhealth.org   
United States, Nebraska
Nebraska Cancer Specialists Recruiting
Omaha, Nebraska, United States, 68114
Contact: Ralph Hauke, M.D.    402-354-8124      
Contact: Kim Bland, R.N.    402-354-5144    kbland@mnhs.org   
United States, New York
Tisch Cancer Institute at Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Matthew Galsky, M.D.    212-241-8214    matthew.galsky@mssm.edu   
United States, Texas
Texas Oncology, PA Recruiting
Dallas, Texas, United States, 75246
Contact: Thomas Hutson, D.O.    214-648-1929      
United States, Virginia
Virginia Oncology Associates Recruiting
Norfolk, Virginia, United States, 23502
Contact: Mark Fleming, M.D.    757-213-5813    mark.fleming@usoncology.com   
Contact: Wendi Gobhart    757.213.5813    wendi.gobhart@usoncology.com   
Sponsors and Collaborators
Hoosier Cancer Research Network
Bristol-Myers Squibb
Investigators
Study Chair: Matthew Galsky, M.D. Hoosier Cancer Research Network
  More Information

Additional Information:
No publications provided

Responsible Party: Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT01524991     History of Changes
Other Study ID Numbers: GU10-148
Study First Received: January 30, 2012
Last Updated: July 1, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Cisplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 18, 2014