Brief Title
First-Line Gemcitabine, Cisplatin + Ipilimumab for Metastatic Urothelial Carcinoma
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
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
Median Overall Survival
Secondary Outcome
Progression-Free Survival
Condition
Urothelial Carcinoma
Intervention
Gemcitabine
Study Arms / Comparison Groups
Treatment
Description: Gemcitabine 1000 mg/m2 Days 1 & 8 Cisplatin 70 mg/m2 Day 1 Ipilimumab 10 mg/kg Day 1 (start cycle 3)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
36
Start Date
January 2012
Completion Date
December 31, 2018
Primary Completion Date
July 15, 2017
Eligibility 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)
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Matthew Galsky, M.D., ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01524991
Organization ID
GU10-148
Responsible Party
Sponsor
Study Sponsor
Hoosier Cancer Research Network
Collaborators
Bristol-Myers Squibb
Study Sponsor
Matthew Galsky, M.D., Study Chair, Hoosier Cancer Research Network
Verification Date
July 2022