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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01524991
Recruitment Status : Active, not recruiting
First Posted : February 2, 2012
Last Update Posted : July 13, 2018
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Hoosier Cancer Research Network

Tracking Information
First Submitted Date  ICMJE January 30, 2012
First Posted Date  ICMJE February 2, 2012
Last Update Posted Date July 13, 2018
Actual Study Start Date  ICMJE January 2012
Actual Primary Completion Date July 15, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2012)
One-Year Overall Survival [ Time Frame: 12 months ]
To determine the 1-year overall survival of patients with advanced/metastatic urothelial cancer treated with gemcitabine, cisplatin, plus ipilimumab.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01524991 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2013)
  • Progression-Free Survival [ Time Frame: 12 months ]
    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 ]
    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 ]
    To determine the safety of treatment with gemcitabine, cisplatin, plus ipilimumab.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2012)
  • Progression-Free Survival [ Time Frame: 12 months ]
    To determine the progression-free survival (using irRC) of patients with advanced/metastatic urothelial carcinoma treated with gemcitabine, cisplatin, and ipilimumab.
  • Best Overall Response Rate [ Time Frame: 12 months ]
    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 ]
    To determine the safety of treatment with gemcitabine, cisplatin, plus ipilimumab.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE First-Line Gemcitabine, Cisplatin + Ipilimumab for Metastatic Urothelial Carcinoma
Official Title  ICMJE Phase II Trial of Gemcitabine, Cisplatin, Plus Ipilimumab as First-line Treatment for Patients With Metastatic Urothelial Carcinoma: Hoosier Cancer Research Network GU10-148
Brief Summary 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.
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Urothelial Carcinoma
Intervention  ICMJE
  • 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)
Study Arms  ICMJE Experimental: Treatment
Gemcitabine 1000 mg/m2 Days 1 & 8 Cisplatin 70 mg/m2 Day 1 Ipilimumab 10 mg/kg Day 1 (start cycle 3)
Interventions:
  • Drug: Gemcitabine
  • Drug: Cisplatin
  • Drug: Ipilimumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 31, 2012)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2018
Actual Primary Completion Date July 15, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01524991
Other Study ID Numbers  ICMJE GU10-148
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoosier Cancer Research Network
Study Sponsor  ICMJE Hoosier Cancer Research Network
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Study Chair: Matthew Galsky, M.D. Hoosier Cancer Research Network
PRS Account Hoosier Cancer Research Network
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP