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.
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
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
Patients who have not recovered from adverse events due to prior systemic anti-cancer therapy (i.e., have residual toxicities > grade 1 of the Common Terminology Criteria for Adverse Events [CTCAE] version [v]5, pre-treatment baseline or to a level permitted under other sections of inclusion/exclusion criteria) with the exception of alopecia or electrolyte abnormalities that can be corrected to =< grade 1 prior to treatment initiation
Single group
Atezolizumab
Biological/VaccineGiven PO
Bevacizumab
Biological/VaccineGiven IV
Biopsy Procedure
Procedure/SurgeryUndergo biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood collection
Bone Scan
Procedure/SurgeryUndergo bone scan
Computed Tomography
Procedure/SurgeryUndergo CT without contrast
Computed Tomography with Contrast
Procedure/SurgeryUndergo CT with contrast
Erlotinib
DrugGiven PO
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Positron Emission Tomography
Procedure/SurgeryUndergo PET
Sodium Fluoride F-18
DrugGiven F-18 sodium fluoride
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.
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.
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.
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.
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