Atezolizumab and CYT107 in Treating Participants With Locally Advanced, Inoperable, or Metastatic Urothelial Carcinoma

Completed · Phase 2

Conditions studied: Advanced Bladder Urothelial Carcinoma, Advanced Ureter Urothelial Carcinoma, Metastatic Bladder Urothelial Carcinoma, Metastatic Renal Pelvis Urothelial Carcinoma, Metastatic Ureter Urothelial Carcinoma, Metastatic Urethral Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Recurrent Bladder Urothelial Carcinoma, Recurrent Renal Pelvis Urothelial Carcinoma, Recurrent Ureter Urothelial Carcinoma, Recurrent Urethral Urothelial Carcinoma, Stage III Bladder Cancer AJCC v8, Stage III Renal Pelvis Cancer AJCC v8, Stage III Ureter Cancer AJCC v8, Stage III Urethral Cancer AJCC v8, Stage IV Bladder Cancer AJCC v8, Stage IV Renal Pelvis Cancer AJCC v8, Stage IV Ureter Cancer AJCC v8, Stage IV Urethral Cancer AJCC v8, Stage IVA Bladder Cancer AJCC v8, Stage IVB Bladder Cancer AJCC v8, Unresectable Bladder Urothelial Carcinoma, Unresectable Renal Pelvis Urothelial Carcinoma, Unresectable Ureter Urothelial Carcinoma

In brief

This phase II trial studies how well atezolizumab when given with glycosylated recombinant human interleukin-7 (CYT107) works in treating patients with urothelial carcinoma that has spread to nearby tissue or lymph nodes (locally advanced), cannot be removed by surgery (inoperable), or has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. CYT107 is a biological product naturally made by the body that may stimulate the immune system to destroy tumor cells. Giving atezolizumab and CYT107 may work better in treating patients with locally advanced, inoperable, or metastatic urothelial carcinoma compared to atezolizumab alone.

Key facts

Study ID

NCT03513952

Run by

National Cancer Institute (NCI)

People needed

47

Starts

2019-06-05

Expected to finish

2024-04-01

Last updated by the study team

2024-07-26

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have histologically or cytologically documented locally advanced/inoperable or metastatic urothelial bladder carcinoma (UBC), including renal pelvis, ureters, urinary bladder, and urethra
• Note: Mixed histology tumors allowed if predominant histology is urothelial carcinoma
• Note: Small cell or neuroendocrine carcinoma is not allowed if predominant
• Patients must have recurrent disease after any prior platinum-based chemotherapy regimen
• Patients must have measurable disease per RECIST 1.1 assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI)
• ECOG performance status =< 2 (Karnofsky >= 60%)
• Patients must have a life expectancy of greater or equal to 12 weeks
• Leukocytes >= 2,500/mcL
• Absolute neutrophil count >= 1,000/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 8 g/dL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert's disease who have serum bilirubin level =< 3 x ULN may be enrolled)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN (AST and/or ALT=< 5 x ULN for patients with liver involvement)
• Alkaline phosphatase =< 2.5 x ULN (=< 5 x ULN for patients with documented liver involvement or bone metastases)
• Creatinine clearance >= 30 mL/min/1.73 m\^2 by Cockcroft-Gault
• At the discretion of the treating physician, a 24-hour urine creatinine clearance could be obtained and utilized as the gold standard if creatinine clearance by Cockcroft-Gault is < 30, and prevents patient enrollment on the trial
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose)
• Patients must provide tissue from an archival tumor sample (obtained within 2 years from screening visit) or newly obtained core, punch, or excisional biopsy of a tumor lesion if deemed relatively safe and technically feasible
• Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours before receiving the first dose of study agent(s); if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
• Administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; CYT107 has not been tested for reproductive toxicity yet and may expose to the same risk; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) before study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of study agent; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Patients must have the ability to understand and the willingness to sign a written informed consent document
• Patients positive for human immunodeficiency virus (HIV) are allowed on study, but HIV-positive patients must have:
• A stable regimen of highly active antiretroviral therapy (HAART)
• No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
• A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR)-based tests

You may not qualify if…

• Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
• Patients who have had chemotherapy or radiotherapy within 2 weeks (4 weeks for nitrosoureas or systemic mitomycin C) before the initiation of study treatment
• Patients who have received more than 2 systemic cytotoxic chemotherapy regimens for metastatic urothelial carcinoma
• Note: Prior perioperative chemotherapy is allowed and is not counted as a line of therapy if patient relapsed >= 12 months later and received additional platinum-based chemotherapy for metastatic disease
• Patients who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier (i.e., have residual toxicities > grade 1); however, the following therapies are allowed:
• Hormone-replacement therapy or oral contraceptives
• Herbal therapy >= 1 week before initiation of study treatment (herbal therapy intended as anticancer therapy must be discontinued at least 1 week before initiation of study treatment)
• Palliative radiotherapy for bone metastases > 2 weeks before initiation of study treatment
• Patients who have received prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody, or pathway -targeting agents
• Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:
• Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose
• No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4)
• Patients who have received treatment with any other investigational agent within 4 weeks before initiation of study treatment
• Patients who have received treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks before initiation of study treatment
• Patients who have received treatment with systemic immunosuppressive medications (including, but not limited to, oral prednisone ( > 10 mg/day or equivalent), cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti TNF] agents) within 2 weeks before initiation of study treatment
• Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
• The use of inhaled corticosteroids, and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
• Patients taking bisphosphonate therapy for symptomatic hypercalcemia
• Note: Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
• Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:
• Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:
• Evaluable or measurable disease outside the CNS
• No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
• No history of intracranial hemorrhage or spinal cord hemorrhage
• No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted

Where it is running

• Kaiser Permanente-Riverside — Riverside, California, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• Straub Clinic and Hospital — Honolulu, Hawaii, United States
• University of Hawaii Cancer Center — Honolulu, Hawaii, United States
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
• East Jefferson General Hospital — Metairie, Louisiana, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• Roswell Park Cancer Institute — Buffalo, New York, United States
• FHCC South Lake Union — Seattle, Washington, United States

Full record on ClinicalTrials.gov

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