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

Urothelial Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01524991
• Other study ID #: GU10-148
• Status: Completed
• Phase: Phase 2
• Start date: January 2012
• Est. completion date: December 31, 2018

Study information

• Verified date: July 2022
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 31, 2018
• Est. primary completion date: July 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

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

Locations

Country	Name	City	State
United States	Texas Oncology, PA	Dallas	Texas
United States	City of Hope: Duarte	Duarte	California
United States	IU Health Goshen Hospital	Goshen	Indiana
United States	Indiana University Melvin & Bren Simon Cancer Center	Indianapolis	Indiana
United States	IU Health Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Tisch Cancer Institute at Mount Sinai Medical Center	New York	New York
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Nebraska Cancer Specialists	Omaha	Nebraska

Sponsors (2)

Lead Sponsor	Collaborator
Hoosier Cancer Research Network	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

References & Publications (1)

Galsky MD, Hahn NM, Albany C, Fleming MT, Starodub A, Twardowski P, Hauke RJ, Sonpavde G, Merad M, Gnjatic S, Bhardwaj N, Chippada-Venkata U, Oh WK, Kim-Schulze S. Impact of gemcitabine + cisplatin + ipilimumab on circulating immune cells in patients (pts) with metastatic urothelial cancer (mUC). J Clin Oncol 33:5s, 2015 (suppl; abstr 4586)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median Overall Survival	To determine the median overall survival of patients with advanced/metastatic urothelial cancer treated with gemcitabine, cisplatin, plus ipilimumab, calculated from the date of registration until the date of final analysis, projected to be 48 months from the start of the study.	48 months
Secondary	Progression-Free Survival	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.; Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions". Progression is definied by IrRC as "at least 25% increase in tumor burden compared with nadir (at any single time point) in two consecutive observations at least 4 wk apart."	12 months
Secondary	Best Overall Response Rate	To determine the best overall response rate to treatment with gemcitabine, cisplatin, plus ipilimumab, per RECIST 1.1 criteria.	12 months
Secondary	Number of Adverse Events Experienced by Patients	To determine the safety of treatment with gemcitabine, cisplatin, plus ipilimumab. The highest grade adverse event for each subject is presented.	12 months

External Links

•   Hoosier Cancer Research Network Homepage