Testing of Bevacizumab, Erlotinib, and Atezolizumab in Combination for Advanced-Stage Kidney Cancer

Active:	Yes
Cancer Type:	Kidney Cancer	NCT ID:	NCT04981509
Trial Phases:	Phase II	Protocol IDs:	10466 (primary) 10466 NCI-2021-07744
Eligibility:	12 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	National Cancer Institute LAO
NCI Full Details:	http://clinicaltrials.gov/show/NCT04981509

Summary

This phase II trial studies the effects of combination therapy with bevacizumab, erlotinib, and atezolizumab in treating patients with hereditary leiomyomatosis and kidney cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Bevacizumab is in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumors. This may slow the growth and spread of tumors. Erlotinib is in a class of medications called kinase inhibitors. It works by blocking the action of a protein called EGFR that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. 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. Combination therapy with bevacizumab, erlotinib, and atezolizumab may stabilize or shrink advanced hereditary leiomyomatosis and kidney cancer.

Objectives

PRIMARY OBJECTIVE:
I. To assess the complete response (CR) rate according to standard Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in patients with 1) advanced renal cell cancer (RCC) associated with hereditary leiomyomatosis and renal cell cancer (HLRCC) and 2) advanced sporadic/non-HLRCC papillary renal cell cancer treated with a combination of bevacizumab, erlotinib, and atezolizumab.

SECONDARY OBJECTIVES:
I. To determine the safety and tolerability of the combination of bevacizumab, erlotinib, and atezolizumab.
II. To determine the objective response rate (ORR) as complete response (CR) + partial response (PR).
III. To determine disease control rate (DCR) - confirmed response, or stable disease (SD) lasting for at least 6 months.
IV. To assess progression-free survival time (PFS) according to RECIST 1.1.
V. To assess overall survival (OS).
VI. To assess the duration of response.
VII. To assess response to treatment using immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST).

EXPLORATORY OBJECTIVES:
I. To evaluate immunologic modulation associated with the administered treatment regimen, including:
Ia. Peripheral immune subset analysis before and on treatment;
Ib. Evaluation of relevant soluble factors before and on treatment. (e.g., cytokine profiles);
Ic. Tumor tissue immune infiltration cells before and after treatment (immune microenvironment, CD8/CD4/CD3 cells, T-cell receptor clonality);
Id. Evaluation of tissue PDL1/PD1 expression and their correlation with outcome.
II. To assess specific genomic alterations (including fumarate hydratase [FH], NRF2 pathway) and determine if there is a correlation with clinical outcomes.

OUTLINE:
Patients receive bevacizumab intravenously (IV) over 30-90 minutes and atezolizumab IV over 30-60 minutes on day 1 of each cycle. Patients also receive erlotinib orally (PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) with or without contrast and magnetic resonance imaging (MRI) throughout the trial. Patients undergo collection of blood throughout the trial, and may undergo a biopsy during screening, as well as a brain MRI/CT scan with contrast, bone scan, and/or F-18 sodium fluoride positron emission tomography (PET) scan as clinically indicated.

After completion of study treatment, patients are followed up every 6 months.

Treatment Sites in Georgia

Emory Saint Joseph's Hospital
5665 Peachtree Dunwoody Road NE
Atlanta, GA 30342
www.emoryhealthcare.org

Emory University Hospital - Midtown
550 Peachtree Street NE
Atlanta, GA 30308
404-686-4411
www.emoryhealthcare.org

Winship Cancer Institute of Emory University
1365 Clifton Road NE
Building C
Atlanta, GA 30322
winshipcancer.emory.edu

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.