Gemcitabine + Carboplatin + Nivolumab Versus Gemcitabine + Oxaliplatin + Nivolumab in Cisplatin-ineligible Patients With Metastatic Urothelial Cancer

NCT03451331 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HCRN GU16-287
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 6

Brief Summary

This is a randomized phase 2 trial of gemcitabine + carboplatin + nivolumab or gemcitabine + oxaliplatin + nivolumab for the treatment of cisplatin-ineligible patients with metastatic urothelial cancer. Randomization will be stratified on the lymph node only (and/or unresectable primary) metastatic status.

Conditions

Metastatic Urothelial Cancer

Keywords

cisplatin-ineligible; gemcitabine; carboplatin; nivolumab; oxaliplatin

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. ORR is defined as the percentage of patients who achieve a response (confirmed PR or CR) according to RECIST 1.1.

  Up to a maximum of 50 months

Secondary Outcomes (4)

• Adverse Events

  AE had been recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 19 months.

• Duration of Response (DOR)

  Up to a maximum of 50 months

• Progression-Free Survival (PFS)

  Up to maximum of 50 months

• Overall Survival (OS)

  Up to a maximum of 53 months

Study Arms (2)

Arm A

EXPERIMENTAL

Gemcitabine plus carboplatin plus nivolumab

Drug: Nivolumab; Drug: Gemcitabine; Drug: Carboplatin

Arm B

EXPERIMENTAL

Gemcitabine plus oxaliplatin plus nivolumab

Drug: Nivolumab; Drug: Gemcitabine; Drug: Oxaliplatin

Interventions

Nivolumab DRUG

Nivolumab 360mg (and/or) Maintenance Single Agent Nivolumab 480mg (starting \~ 2-4 weeks after completing combination chemotherapy plus nivolumab)

Also known as: OPDIVO®

Arm A; Arm B

Gemcitabine DRUG

1000 mg/m\^2

Also known as: Gemzar

Arm A; Arm B

Carboplatin DRUG

AUC 4.5 (based on the Calvert formula)

Also known as: Paraplatin®

Arm A

Oxaliplatin DRUG

130 mg/m\^2

Also known as: Eloxatin

Arm B

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of = 2
• Able to comply with the study protocol, in the investigator's judgment.
• Histologically documented, locally advanced (T4b, any N; or any T, N 2-3) or metastatic urothelial carcinoma (mUC) (M1, Stage IV) (also termed TCC or UCC of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra) Patients with mixed histologies are required to have a dominant transitional cell pattern. Locally advanced bladder cancer must be inoperable on the basis of involvement of pelvic sidewall or adjacent viscera (clinical Stage T4b) or bulky nodal metastasis (N2-N3).
• Measurable disease, as defined by RECIST v1.1
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens (metastatic specimens preferable but if not available primary tumor specimens that are at least muscle-invasive are acceptable) in paraffin blocks (blocks preferred) or at least 15 unstained slides. If archival tissue is not available, subjects may be considered for enrollment on a case by case basis after discussion with the sponsor-investigator.
• No prior chemotherapy for inoperable locally advanced or mUC. For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation for urothelial carcinoma, a treatment-free interval \> 12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment naive in the metastatic setting.
• Cisplatin-ineligible as defined by at least one of the following:
• Calculated creatinine clearance ≥ 30 (Cockroft-Gault)
• ECOG performance status of 2 or greater
• CTCAE v4 Grade ≥ 2 audiometric hearing loss
• Demonstrate adequate organ function. All screening labs to be obtained within 28 days prior to registration:
• Hematological:
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 10\^9/L

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Active infection requiring systemic therapy.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Any serious or uncontrolled medical disorder that, in the opinion of the site investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
• Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
• Grade ≥ 2 neuropathy (NCI CTCAE version 4).
• Known positive result for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (RNA) or hepatitis C antibody (HCV antibody) indicating acute or chronic infection. Testing at screening is not required.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class III or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina.
• Known left ventricular ejection fraction (LVEF) \< 40% Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF 40%-50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
• Solid organ or tissue transplant including stem cell transplant

Sponsors & Collaborators

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

Study Sites (6)

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

John Theuer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Huntsman Cancer Institute University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Galsky MD, Daneshmand S, Izadmehr S, Gonzalez-Kozlova E, Chan KG, Lewis S, Achkar BE, Dorff TB, Cetnar JP, Neil BO, D'Souza A, Mamtani R, Kyriakopoulos C, Jun T, Gogerly-Moragoda M, Brody R, Xie H, Nie K, Kelly G, Horowitz A, Kinoshita Y, Ellis E, Nose Y, Ioannou G, Cabal R, Del Valle DM, Haines GK, Wang L, Mouw KW, Samstein RM, Mehrazin R, Bhardwaj N, Yu M, Zhao Q, Kim-Schulze S, Sebra R, Zhu J, Gnjatic S, Sfakianos J, Pal SK. Gemcitabine and cisplatin plus nivolumab as organ-sparing treatment for muscle-invasive bladder cancer: a phase 2 trial. Nat Med. 2023 Nov;29(11):2825-2834. doi: 10.1038/s41591-023-02568-1. Epub 2023 Oct 2.

  PMID: 37783966 DERIVED

Related Links

• Hoosier Cancer Research Network Website

MeSH Terms

Interventions

Nivolumab; Gemcitabine; Carboplatin; Oxaliplatin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

317-921-2050

Study Officials

• Matthew Galsky, M.D.

  Icahn School of Medicine at Mount Sinai; Tisch Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open-label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: February 23, 2018
• First Posted: March 1, 2018
• Study Start: May 10, 2018
• Primary Completion: June 7, 2023
• Study Completion: July 28, 2023
• Last Updated: May 16, 2024
• Results First Posted: May 16, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)