Testing of Bevacizumab, Erlotinib, and Atezolizumab in Combination for Advanced-Stage Kidney Cancer
A Phase 2 Study of Bevacizumab, Erlotinib and Atezolizumab in Subjects With Advanced Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) Associated or Sporadic Papillary Renal Cell Cancer
3 other identifiers
interventional
65
1 country
13
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jun 2022
Longer than P75 for phase_2
13 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
July 28, 2021
CompletedFirst Posted
Study publicly available on registry
July 29, 2021
CompletedStudy Start
First participant enrolled
June 10, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
April 21, 2026
April 1, 2026
5.6 years
July 28, 2021
April 18, 2026
Conditions
Outcome Measures
Primary Outcomes (7)
Incidence of adverse events
To determine the safety and tolerability of the combination of bevacizumab, erlotinib, and atezolizumab, the fraction of patients with a dose-limiting toxicity will be reported, along with the maximum grade and type of toxicity for each type noted. Note: In addition to adverse events in the entire study population, pediatric toxicities will also be reported and analyzed separately.
Up to 28 days after treatment
Objective response rate
Defined as complete response (CR) + partial response (PR), the fraction with a response (CR+PR) will be reported separately by cohort, along with a 95% confidence interval.
Up to 2 years from study enrollment
Disease control rate
Will be reported for patients with confirmed response, or stable disease (SD) lasting for at least 6 months. Will be reported separately by cohort, along with a 95% confidence interval.
Up to 2 years from study enrollment
Progression-free survival time (PFS)
Assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, PFS will be determined using the Kaplan-Meier method, and the curves presented along with a 95% confidence interval on the median PFS, separately by cohort.
Time from study treatment initiation until disease progression or death, assessed up to 2 years from study enrollment
Overall survival (OS)
The Kaplan-Meier method will be used and the curves presented along with a 95% confidence interval on the median OS, separately by cohort.
From study treatment initiation until death from any cause, assessed up to 2 years from study enrollment
Duration of response (DOR)
The Kaplan-Meier method will be used and the curves presented along with a 95% confidence interval on the median DOR, separately by cohort.
Length of time without disease progression or recurrence, up to 2 years from study enrollment
Response to treatment
Response to treatment using immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST), the fraction with a response (CR+PR) according to iRECIST will be reported separately by cohort, along with a 95% confidence interval.
Assessed up to 2 years from study enrollment
Study Arms (1)
Treatment (bevacizumab, atezolizumab, erlotinib)
EXPERIMENTALPatients receive bevacizumab IV over 30-90 minutes and atezolizumab IV over 30-60 minutes on day 1 of each cycle. Patients also receive erlotinib PO 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 CT with or without contrast and 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 PET scan as clinically indicated.
Interventions
Given PO
Given IV
Undergo biopsy
Undergo blood collection
Undergo bone scan
Undergo CT without contrast
Undergo CT with contrast
Undergo MRI
Undergo PET
Given F-18 sodium fluoride
Eligibility Criteria
You may qualify if:
- Patients must have:
- A diagnosis of HLRCC with a histologic or cytologic confirmation of RCC consistent with this diagnosis (Cohort 1) OR
- Cytologically or histologically confirmed sporadic/non-HLRCC papillary renal cell carcinoma (presence of papillary component) (Cohort 2)
- Patients must have advanced RCC with measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) by chest x-ray or as \>= 10 mm (\>= 1 cm) with CT scan, MRI, or calipers by clinical exam. To be considered pathologically enlarged and measurable, a lymph node must be \>= 15 mm (\>= 1.5 cm) in short axis
- Patients must have received no more than two prior regimens targeting the VEGF pathway and no prior bevacizumab therapy in the metastatic/advanced setting. No prior treatment with PD-1 or PD-L1 inhibitors in the metastatic/advanced setting. No prior therapy is required for eligibility
- Age \>= 12 years
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Absolute neutrophil count \>= 1,000/mcL
- Platelets \>= 100,000/mcL
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (\< 3 x upper limit of reference range in patients with known/suspected Gilbert's disease)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (or =\< 5 x upper limit of reference range if considered to be related to liver or bone metastases by the principal investigator \[PI\])
- Alkaline phosphatase =\< 2.5 x institutional ULN (or =\< 5 x upper limit of reference range if considered to be related to liver or bone metastases by the PI)
- Note: For pediatric patients (\< 18 years of age), ULN for alkaline phosphatase will be defined as 390 IU/L for males and 320 IU/L for females
- Glomerular filtration rate (GFR) \>= 30 mL/min/1.73 m\^2
- Note: For pediatric patients (\< 18 years of age) the following creatinine thresholds will be utilized. Patients with a creatinine that exceeds this threshold will require further testing with a confirmation of GFR \>= 40 as determined by either 24-hour urine collection or with radioisotope based nuclear medicine evaluation
- +13 more criteria
You may not qualify if:
- Any prior systemic therapy to treat the patient's kidney cancer within 4 weeks or, if known, 5 half-lives of the prior agent (whichever is shorter) prior to cycle 1 day 1
- Other prior therapies for kidney cancer: Radiotherapy \< 2 weeks prior to cycle 1, day 1
- Major surgical procedure \< 28 days before cycle 1, day 1. Surgical wounds must be healed prior to starting therapy
- Treatment with any other investigational agent within 4 weeks prior to cycle 1, day 1
- Treatment with systemic immunostimulatory agents (including, but not limited to, interferon \[IFN\]-alpha or interleukin \[IL\]-2) within 6 weeks prior to cycle 1, day 1
- Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to cycle 1, day 1
- Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea or for purposes of pre-medication prior to radiology studies) may be enrolled
- The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
- Hypercalcemia \> grade 1 of the CTCAE v5 that is not corrected prior to treatment initiation
- Patients taking bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
- History of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
- Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible
- Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible
- Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
- Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
- +24 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (13)
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342, United States
Northwestern University
Chicago, Illinois, 60611, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
NCI - Center for Cancer Research
Bethesda, Maryland, 20892, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
NYU Langone Hospital - Long Island
Mineola, New York, 11501, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ramaprasad Srinivasan
National Cancer Institute LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 28, 2021
First Posted
July 29, 2021
Study Start
June 10, 2022
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2027
Last Updated
April 21, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.