Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types
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|ClinicalTrials.gov Identifier: NCT05000294|
Recruitment Status : Suspended (internal drug dispensation issue)
First Posted : August 11, 2021
Last Update Posted : July 21, 2022
Checkpoint inhibitor therapy represents a significant advance in cancer care. The interaction between PD-1 and PD-L1 induces immune tolerance, and the inhibition of this interaction is an effective treatment strategy for numerous malignancies.
Despite its demonstrated potential, immunotherapy is not currently thought to be an effective intervention in the treatment of several immunologically "cold" tumors such as prostate cancer, biliary tract cancers, soft tissue sarcomas, well-differentiated neuroendocrine tumors, microsatellite stable colorectal cancer, pancreatic cancer, and non-triple negative breast cancer.
Vascular endothelial growth factor (VEGF) is thought to play a key role in modulating the anti-tumor immune response. Vascular endothelial growth factor (VEGF) is secreted by tumors and leads to endothelial cell proliferation, vascular permeability, and vasodilation. This in turn leads to the development of an abnormal vasculature with excessive permeability and poor blood flow, limiting immune surveillance. In addition, VEGF inhibits dendritic cell differentiation, limiting the presentation of tumor antigens to CD4 and CD8 T cells. Vascular endothelial growth factor (VEGF). VEGF tyrosine kinase inhibitors (TKIs) VEGF-TKIs are currently utilized in the treatment of a variety of malignancies and are widely utilized in combination with checkpoint blockade in the treatment of clear cell kidney cancer.
Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade even in tumors which have traditionally been thought to be unresponsive to immunotherapy. This study aims to evaluate the combination of the immune checkpoint inhibitor atezolizumab and the VEGF-TKI tivozanib in a variety of tumors which have a low response rate to checkpoint inhibitor therapy alone.
|Condition or disease||Intervention/treatment||Phase|
|Bile Duct Cancer Gall Bladder Cancer Breast Cancer Neuroendocrine Tumors Ovarian Cancer Pancreatic Adenocarcinoma Soft Tissue Sarcoma Vulvar Cancer Prostate Cancer||Drug: Atezolizumab Drug: Tivozanib||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||29 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types|
|Actual Study Start Date :||November 3, 2021|
|Estimated Primary Completion Date :||June 2023|
|Estimated Study Completion Date :||June 2024|
|Experimental: Atezolizumab + Tivozanib||
Subjects on both the phase Ib and phase II portions of this study will receive 1680 mg intravenously of atezolizumab on Day 1 of each 28 day cycle.
Other Name: Tecentriq
Subjects in both the phase Ib and phase II portions of the study will take tivozanib orally once daily on Days 1-21 of each 28 day cycle. Subjects on the phase Ib will be assigned to receive either 1.34 mg/day (Dose level 0) or 0.89 mg/day (Dose level -1). Subjects in the phase II portion of the study will receive 0.89 mg/day.
Other Name: Fotivda
- Objective response rate (ORR) [ Time Frame: 30 months ]To determine the best overall response rate (ORR) of atezolizumab plus tivozanib in subjects with immunologically cold tumors
- Progression free survival (PFS) [ Time Frame: 30 months ]To determine the progression free survival (PFS) of subjects with immunologically cold tumors receiving atezolizumab plus tivozanib
- Overall survival (OS) [ Time Frame: 30 months ]To determine the overall survival (OS) of subjects with immunologically cold tumors receiving atezolizumab plus tivozanib.
- Disease control rate (DCR) [ Time Frame: 30 months ]To determine the disease control rate (DCR) of subjects with immunologically cold tumors receiving atezolizumab plus tivozanib. DCR is defined as percentage of subjects who achieve complete response, partial response and stable disease during the course of study using RECIST v1.1 criteria.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05000294
|United States, Florida|
|University of Florida|
|Gainesville, Florida, United States, 32608|
|Principal Investigator:||Jonathan Chatzkel, MD||University of Florida|
|Principal Investigator:||Brian Ramnaraign, MD||University of Florida|