Ignite Creation Date:
2024-05-06 @ 11:25 AM
Last Modification Date:
2024-10-26 @ 12:45 PM
Study NCT ID:
NCT03513952
Status:
COMPLETED
Last Update Posted:
2024-07-03
First Post:
2018-05-01
Brief Title:
Atezolizumab and CYT107 in Treating Participants With Locally Advanced Inoperable or Metastatic Urothelial Carcinoma
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Randomized Phase II Study of Atezolizumab MPDL3280A Plus Recombinant Human IL7 CYT107 in Patients With Locally Advanced or Metastatic Urothelial Carcinoma
Status:
COMPLETED
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 bodys 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
Detailed Description:
PRIMARY OBJECTIVE
I To determine the clinical efficacy of the investigational treatment combination
SECONDARY OBJECTIVES
I To determine the clinical activity and toxicity of the investigational treatment combination
II The clinical benefit rate CBR progression-free survival PFS duration of response DOR as measured by Response Evaluation Criteria in Solid Tumors RECIST 11 and immune-related response criteria irRC and overall survival OS
III The CBR PFS DOR and OS in all patients and patients stratified by PD-L1 expression levels in the tumor microenvironment
IV The safety and toxicity of addition of CYT107 to atezolizumab
EXPLORATORY OBJECTIVES
I To determine the immune correlates of the clinical activity of the investigational treatment combination
II Explore the effect of the investigational treatment combination on the number and phenotype of tumor-specific T cells in the peripheral blood
III Investigate for evidence that the investigational treatment combination increases the exposure of bladder cancer-specific antigens eg cancertestis antigens or neoantigens
IV Investigate changes in tumor microenvironment that correlate with response or provide information on potential actionable causes for lack of clinical benefit
V Investigate the potential that administration of atezolizumab with CYT107 may perturb the pharmacokinetics and immunogenicity of CYT107
OUTLINE
SAFETY RUN-IN PHASE Patients 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
Patients are randomized to 1 of 2 groups
GROUP 1 experimental arm Patients receive CYT107 intramuscularly IM on days 1 8 15 and 22 and atezolizumab intravenously 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 computed tomography CT andor magnetic resonance imaging MRI scans and collection of blood and stool samples on study Patients may also undergo tumor biopsy at screening and on study
GROUP 2 control arm Patients 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 andor MRI scans and collection of blood and stool samples on study Patients may also undergo tumor biopsy at screening and on study
After completion of study treatment patients are followed up at 30 days and then every 12 weeks for up to 2 years
I To determine the clinical efficacy of the investigational treatment combination
SECONDARY OBJECTIVES
I To determine the clinical activity and toxicity of the investigational treatment combination
II The clinical benefit rate CBR progression-free survival PFS duration of response DOR as measured by Response Evaluation Criteria in Solid Tumors RECIST 11 and immune-related response criteria irRC and overall survival OS
III The CBR PFS DOR and OS in all patients and patients stratified by PD-L1 expression levels in the tumor microenvironment
IV The safety and toxicity of addition of CYT107 to atezolizumab
EXPLORATORY OBJECTIVES
I To determine the immune correlates of the clinical activity of the investigational treatment combination
II Explore the effect of the investigational treatment combination on the number and phenotype of tumor-specific T cells in the peripheral blood
III Investigate for evidence that the investigational treatment combination increases the exposure of bladder cancer-specific antigens eg cancertestis antigens or neoantigens
IV Investigate changes in tumor microenvironment that correlate with response or provide information on potential actionable causes for lack of clinical benefit
V Investigate the potential that administration of atezolizumab with CYT107 may perturb the pharmacokinetics and immunogenicity of CYT107
OUTLINE
SAFETY RUN-IN PHASE Patients 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
Patients are randomized to 1 of 2 groups
GROUP 1 experimental arm Patients receive CYT107 intramuscularly IM on days 1 8 15 and 22 and atezolizumab intravenously 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 computed tomography CT andor magnetic resonance imaging MRI scans and collection of blood and stool samples on study Patients may also undergo tumor biopsy at screening and on study
GROUP 2 control arm Patients 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 andor MRI scans and collection of blood and stool samples on study Patients may also undergo tumor biopsy at screening and on study
After completion of study treatment patients are followed up at 30 days and then every 12 weeks for up to 2 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2018-00684 | REGISTRY | None | None |
| CITN-14 | OTHER | None | None |
| CITN-14 | OTHER | None | None |
| P30CA015704 | NIH | None | None |
| U01CA154967 | NIH | CTEP | httpsreporternihgovquickSearchU01CA154967 |