Atezolizumab and CYT107 in Treating Participants With Locally Advanced, Inoperable, or Metastatic Urothelial Carcinoma
A Randomized Phase II Study of Atezolizumab (MPDL3280A) Plus Recombinant Human IL7 (CYT107) in Patients With Locally Advanced or Metastatic Urothelial Carcinoma
4 other identifiers
interventional
47
1 country
9
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jun 2019
Longer than P75 for phase_2
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 1, 2018
CompletedFirst Posted
Study publicly available on registry
May 2, 2018
CompletedStudy Start
First participant enrolled
June 5, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2024
CompletedResults Posted
Study results publicly available
July 3, 2024
CompletedJuly 26, 2024
May 1, 2024
4.3 years
May 1, 2018
April 19, 2024
July 2, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Objective Response Rate (ORR)
ORR is defined as the proportion of patients who have achieved Complete Response (CR) - disappearance of all target lesions or Partial Response (PR) - \>=30% decrease in the sum of the longest diameter of target lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; Overall Response (OR) = CR + PR.
Up to 2 years
Secondary Outcomes (4)
Clinical Benefit Rate (CBR) Measured by RECIST v1.1
Up to 2 years
Progression-free Survival (PFS)
Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years.
Duration of Response (DOR)
Time interval between the date of first response (CR/PR) and the date of progression, assessed up to 2 years.
Overall Survival (OS)
Time interval between start of treatment to death due to any cause, assessed up to 48 months.
Other Outcomes (1)
Assessment of Investigation Treatment Combination on the Immune-bias of the Tumor Microenvironment
Up to 2 years
Study Arms (3)
Group 1 (CYT107, atezolizumab)
EXPERIMENTALPatients receive CYT107 IM on days 1, 8, 15, and 22, and atezolizumab IV over 60 minutes on day 8 of cycle 1. Following cycle 1, patients receive atezolizumab IV over 30-60 minutes on day 1. Cycles with atezolizumab repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI scans, and collection of blood and stool samples on study. Patients may also undergo tumor biopsy at screening and on study.
Group 2 (atezolizumab)
ACTIVE COMPARATORPatients receive atezolizumab IV over 60 minutes on cycle 1. Following cycle 1, patients receive atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI scans, and collection of blood and stool samples on study. Patients may also undergo tumor biopsy at screening and on study.
Safety run in phase
EXPERIMENTALPatients assigned to the experimental arm (atezolizumab + CYT107). If the treatment combination of the experimental arm demonstrates an acceptable safety profile in the Safety Run-In (one or fewer patient experiences a protocol-defined Dose Limiting-Toxicity), randomized enrollment into the trial will begin. The Run-in phase patients will be analyzed and reported separately both for safety and for efficacy.
Interventions
Given IV
Undergo biopsy of tumor
Undergo collection of blood and stool samples
Undergo CT
Given IM
Correlative studies
Undergo MRI
Undergo PET/CT
Eligibility Criteria
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
- +10 more criteria
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
- +35 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
Kaiser Permanente-Riverside
Riverside, California, 92505, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Straub Clinic and Hospital
Honolulu, Hawaii, 96813, United States
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
East Jefferson General Hospital
Metairie, Louisiana, 70006, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
FHCC South Lake Union
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Cancer Immunotherapy Trials Network Trial Manager
- Organization
- Fred Hutchinson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Evan Y Yu
Cancer Immunotherapy Trials Network
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 1, 2018
First Posted
May 2, 2018
Study Start
June 5, 2019
Primary Completion
September 30, 2023
Study Completion
April 1, 2024
Last Updated
July 26, 2024
Results First Posted
July 3, 2024
Record last verified: 2024-05