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

This study is ongoing, but not recruiting participants.
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: January 8, 2015
Last verified: January 2015
  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 Cancer Research Network 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

Locations
United States, California
City of Hope: Duarte
Duarte, California, United States, 91010
United States, Indiana
IU Health Goshen Hospital
Goshen, Indiana, United States, 46527
Indiana University Melvin & Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
IU Health Central Indiana Cancer Centers
Indianapolis, Indiana, United States, 46219
United States, Nebraska
Nebraska Cancer Specialists
Omaha, Nebraska, United States, 68114
United States, New York
Tisch Cancer Institute at Mount Sinai Medical Center
New York, New York, United States, 10029
United States, Texas
Texas Oncology, PA
Dallas, Texas, United States, 75246
United States, Virginia
Virginia Oncology Associates
Norfolk, Virginia, United States, 23502
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: January 8, 2015
Health Authority: United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on March 26, 2015