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

NCT01524991 | Completed Phase 2 Results DMC

• 1 other identifier: GU10-148
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 8

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.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Progression-Free Survival

  12 months

• Best Overall Response Rate

  12 months

• Number of Adverse Events Experienced by Patients

  12 months

Study Arms (1)

Treatment

EXPERIMENTAL

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

Drug: Gemcitabine; Drug: Cisplatin; Drug: Ipilimumab

Interventions

Gemcitabine DRUG

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

Treatment

Cisplatin DRUG

Cisplatin 70 mg/m2 Day 1 (all cycles)

Treatment

Ipilimumab DRUG

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

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hoosier Cancer Research Network: lead
• Bristol-Myers Squibb: collaborator

Study Sites (8)

City of Hope: Duarte

Duarte, California, 91010, United States

Location

IU Health Goshen Hospital

Goshen, Indiana, 46527, United States

Location

Indiana University Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

IU Health Central Indiana Cancer Centers

Indianapolis, Indiana, 46219, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68114, United States

Location

Tisch Cancer Institute at Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Texas Oncology, PA

Dallas, Texas, 75246, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Related Publications (2)

• 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)

  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.

  PMID: 29248319 DERIVED

Related Links

• Hoosier Cancer Research Network Homepage

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

Gemcitabine; Cisplatin; Ipilimumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Clinicaltrials.gov Results Coordinator
• Organization: Hoosier Cancer Research Network

jsmith@hoosiercancer.org

317-643-5842

Study Officials

• Matthew Galsky, M.D.

  Hoosier Cancer Research Network

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2012
• First Posted: February 2, 2012
• Study Start: January 1, 2012
• Primary Completion: July 15, 2017
• Study Completion: December 31, 2018
• Last Updated: July 11, 2022
• Results First Posted: November 29, 2019

Record last verified: 2022-07

Locations

US (8)