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

NCT ID: NCT01524991

Last Updated: 2022-07-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2018-12-31

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

Conditions

Urothelial Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Gemcitabine 1000 mg/m2 Days 1 \& 8 Cisplatin 70 mg/m2 Day 1 Ipilimumab 10 mg/kg Day 1 (start cycle 3)

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

Gemcitabine 1000 mg/m2 Days 1 \& 8 (all cycles)

Cisplatin

Intervention Type: DRUG

Cisplatin 70 mg/m2 Day 1 (all cycles)

Ipilimumab

Intervention Type: DRUG

Ipilimumab 10 mg/kg Day 1 (start cycle 3)

Interventions

Gemcitabine

Gemcitabine 1000 mg/m2 Days 1 \& 8 (all cycles)

Intervention Type: DRUG

Cisplatin

Cisplatin 70 mg/m2 Day 1 (all cycles)

Intervention Type: DRUG

Ipilimumab

Ipilimumab 10 mg/kg Day 1 (start cycle 3)

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Hoosier Cancer Research Network

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew Galsky, M.D.

Role: STUDY_CHAIR

Hoosier Cancer Research Network

Locations

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

Nebraska Cancer Specialists

Omaha, Nebraska, United States

Tisch Cancer Institute at Mount Sinai Medical Center

New York, New York, United States

Texas Oncology, PA

Dallas, Texas, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Countries

United States

References

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)

Reference Type: BACKGROUND

Galsky MD, Wang H, Hahn NM, Twardowski P, Pal SK, Albany C, Fleming MT, Starodub A, Hauke RJ, Yu M, Zhao Q, Sonpavde G, Donovan MJ, Patel VG, Sfakianos JP, Domingo-Domenech J, Oh WK, Akers N, Losic B, Gnjatic S, Schadt EE, Chen R, Kim-Schulze S, Bhardwaj N, Uzilov AV. Phase 2 Trial of Gemcitabine, Cisplatin, plus Ipilimumab in Patients with Metastatic Urothelial Cancer and Impact of DNA Damage Response Gene Mutations on Outcomes. Eur Urol. 2018 May;73(5):751-759. doi: 10.1016/j.eururo.2017.12.001. Epub 2017 Dec 13.

Reference Type: DERIVED

PMID: 29248319 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.hoosiercancer.org

Hoosier Cancer Research Network Homepage

Other Identifiers

GU10-148

Identifier Type: -

Identifier Source: org_study_id