Gemcitabine Hydrochloride, Cisplatin, and Ipilimumab as First-Line Therapy in Treating Patients With Metastatic Urothelial Cancer
Basic Trial Information
|Phase II||Treatment||Active||18 and over||GU10-148|
NCI-2013-00250, 1110007307, NCT01524991
This phase II clinical trial studies how well gemcitabine hydrochloride, cisplatin, and ipilimumab work as first-line therapy in treating patients with metastatic urothelial cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of tumors to grow and spread. Other find tumor cells and help kill them or carry tumor-killing substances to them. Giving gemcitabine hydrochloride and cisplatin together with ipilimumab may kill more tumor cells.
Further Study Information
I. To determine the 1-year overall survival of patients with advanced/metastatic urothelial cancer treated with gemcitabine (gemcitabine hydrochloride), cisplatin, plus ipilimumab.
I. To determine the progression-free survival (using immune-related response criteria [irRC]) of patients with advanced/metastatic urothelial carcinoma treated with gemcitabine, cisplatin, and ipilimumab.
II. To determine the disease control rate (complete response + partial response + stable disease using irRC and Response Evaluation Criteria in Solid Tumors (RECIST) to treatment with gemcitabine, cisplatin, plus ipilimumab.
III. To determine the safety of treatment with gemcitabine, cisplatin, plus ipilimumab.
I. To serially monitor the global composition immune cells in the blood by polychromatic flow cytometry and correlate changes with clinical outcome.
II. To determine the frequency of tumor-antigen specific cluster of differentiation 8 (CD8)+ T cells by antigen-specific multicytokine production (interferon gamma [IFN-g], tumor necrosis factor alpha [TNF-a] and interleukin 2 [IL-2]) by intracellular cytokine staining.
III. To perform transcriptional profiling of blood samples before and after treatment using microarray and correlate changes with clinical outcomes.
INDUCTION: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8, cisplatin IV on day 1, and ipilimumab IV over 90 minutes on day 1 (courses 3-6 only). Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Beginning week 28, patients receive ipilimumab IV over 90 minutes on day 1. Courses repeat every 3 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information; note: HIPAA authorization may be included in the informed consent or obtained separately
Karnofsky performance status (KPS) >= 80% within 7 days prior to registration for protocol therapy
Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy 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; WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal; post-menopause is defined as: amenorrhea >= 12 consecutive months without another cause, or for women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level >= 35 mIU/mL; women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [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
Females must not be pregnant or breastfeeding
Histological or cytological proof of urothelial carcinoma of the urethra, bladder, ureters, or renal pelvis
Advanced (clinical stage T4b, unresectable) or metastatic disease
No active central nervous system (CNS) metastases; subjects with neurological symptoms must undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis within 28 days of registration; note: a subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic
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; note: 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
Prior radiation therapy is allowed to < 25% of the bone marrow; note: no radiation therapy within 30 days prior to registration for protocol therapy
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); note: patients with other immune disorders should not be enrolled without discussion with the principal investigator
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 adverse events (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 tumor necrosis factor receptor superfamily, member 9 (CD137) agonist or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor or agonist
No known active or chronic infection with human immunodeficiency virus (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 orally [PO] daily for > 6 months during the past year)
White blood cell count (WBC) >= 3.5K/mm^3
Hemoglobin (Hgb) >= 9 g/dL
Platelets >= 100K/mm^3
Absolute neutrophil count (ANC) >= 1.5K/mm^3
Calculated creatinine clearance of >= 55 cc/min using the Cockcroft-Gault formula
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) =< 2.5 x ULN; note: if the patient has liver metastases present, then =< 5 x ULN
Alanine aminotransferase (ALT) =< 2.5 x ULN; note: if the patient has liver metastases present, then =< 5 x ULN
Patient must consent to mandatory correlative sample collection
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
Hoosier Oncology Group
- National Cancer Institute
Indiana University/Melvin and Bren Simon Cancer Center
Noah M. Hahn
Noah M. Hahn
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01524991
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.