Testing Combination Therapy for Advanced Kidney Cancer
This study is testing a combination of three drugs – bevacizumab, erlotinib, and atezolizumab – for people with advanced kidney cancer. Bevacizumab works by blocking blood vessel growth to tumors, and erlotinib blocks a protein (EGFR) that helps cancer cells multiply. Atezolizumab is an immunotherapy that helps your body's immune system fight cancer. You may be able to join if you have advanced kidney cancer, specifically hereditary leiomyomatosis and renal cell carcinoma (HLRCC) or papillary renal cell carcinoma. The study aims to see how many people have their tumors shrink or disappear, and how safe the treatment is. The current recruitment status is unclear, and the study plans to enroll 65 participants.
- Study design
- This is a Phase II interventional study planning to enroll 65 participants. It is testing a combination of three drugs for advanced kidney cancer.
- What's involved
- You would undergo a biopsy and blood collection, and have bone scans. The study will measure adverse events up to 28 days after treatment, and your response to treatment for up to 2 years.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your response to treatment and disease control will be measured for up to 2 years from study enrollment. Adverse events will be measured up to 28 days after treatment.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04981509
Testing of Bevacizumab, Erlotinib, and Atezolizumab in Combination for Advanced-Stage Kidney Cancer
Recruiting
PHASE2Ages 12+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~65 participants
Updated 2026-09-02 on ClinicalTrials.gov
What's tested:AtezolizumabBevacizumabBiopsy ProcedureBiospecimen CollectionBone ScanComputed Tomography
At a glance
Recruiting sites
5 of 13 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Incidence of adverse events
Measured over Up to 28 days after treatment
+6 more outcomes measured
Conditions
NCT04981509
Where you'd take part
This study runs at 13 sites. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.
Emory Saint Joseph's Hospital
Atlanta, Georgiastudy coordinator listed
Recruiting
Emory University Hospital Midtown
Atlanta, Georgiastudy coordinator listed
Recruiting
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgiastudy coordinator listed
Recruiting
NCI - Center for Cancer Research
Bethesda, Marylandstudy coordinator listed
Recruiting
Ohio State University Comprehensive Cancer Center
Columbus, Ohiostudy coordinator listed
Recruiting
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New Yorkno site contact published
Active, not recruiting
National Institutes of Health Clinical Center
Bethesda, Marylandno site contact published
Suspended
Northwestern University
Chicago, Illinoisno site contact published
Suspended
Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.
Study leadership
- Ramaprasad Srinivasan · PRINCIPAL_INVESTIGATOR · National Cancer Institute LAO
Who to contact
Site Public Contact
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Eligibility criteria
Inclusion
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
Age: 12 to \< 13 years; Maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female)
Age: 13 to \< 16 years; Maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female)
Age: 16 to \< 18 years; Maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)
The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR, utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC)
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with an undetectable viral load within 6 months are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression/recurrence for \>= 3 months and the patient no longer requires more than a physiologic dose of steroids
Patients does not have a prior or concurrent invasive malignancy; patients are eligible if a prior or concurrent invasive malignancy exists, but the natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen
Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
The effects of study drugs on the developing human fetus are unknown. For this reason, all women and men of childbearing potential must agree to use adequate contraception (including but not limited to abstinence, barrier methods, hormonal contraceptives \[birth control pills, injections, or implants\], intrauterine device \[IUD\], tubal ligation, vasectomy) prior to study entry and for 6 months after completion of study therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, and 6 months after completion of study drugs administration
Subjects must provide archival tissue block or unstained tumor tissue or be willing to undergo biopsy to collect samples for retrospective central pathology review
The ability of subject or parent/guardian to understand and the willingness to sign a written informed consent document or subjects with impaired decision making capacity (IDMC) if they are represented by a legally authorized representative (LAR)
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
Rash must cover less than 10% of body surface area (BSA)
The disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
No acute exacerbations of the underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
Patients with untreated latent or active tuberculosis (TB) are excluded
Severe infections within 4 weeks prior to cycle 1, day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
Administration of a live, attenuated vaccine within 4 weeks before cycle 1, day 1 or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of atezolizumab
NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines and are not allowed. Influenza vaccination should be given during influenza season only (approximately October to March)
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Poorly controlled hypertension with at least 2 occasions of elevated blood pressure separated by a 24-hour periodd within a week before treatment initiation, despite optimal medical management. (Adults: resting systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg. Pediatric \[\< 18 years old\]: Blood pressure \[BP\] \>= the 95th percentile for age, height, and sex). History of hypertensive crisis or hypertensive encephalopathy
Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
History of anaphylactic or severe allergic reactions attributed to compounds of similar chemical or biologic composition to the study agents
Patients with myocardial infarction, gastrointestinal (GI) perforation/fistula, intraabdominal abscess, or cerebrovascular accidents within 6 months before cycle 1, day 1
Documented baseline proteinuria \> 1000 mg/day on 24-hour urine collection. Only patients with 1+ or greater proteinuria on urinalysis (UA) and a spot urine protein:creatinine ratio of \> 0.5 will undergo a 24-hour urine collection for quantitation of proteinuria
Pregnant women are excluded from this study because study drugs may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with study drugs, breastfeeding should be discontinued if the mother is treated with study drugs
Serious, non-healing wound or ulcer; bone fracture within 3 months prior to treatment initiation
Concomitant therapy with systemic medications or herbal supplements that are known strong inhibitors or inducers of CYP450 3A4, or strong CYP1A2 inducers. To determine the impact of a concomitant drug on CYP enzymes see the FDA-approved product labeling and/or tertiary compendia (e.g., Inhibitors and Inducers of Cytochrome P450 Enzymes)
Patients who use tobacco or nicotine products and cannot stop their use of these products for the duration of study treatment
Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to cycle 1, day 1
History of or active hemoptysis within 1 month prior to cycle 1 day 1
History of grade \>= 4 venous thromboembolism
History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation)
Current or recent (\< 10 days prior to initiation of study treatment) use of aspirin (\> 325 mg/day), or clopidogrel (\> 75 mg/day)
Note: The use of full-dose oral or parenteral anticoagulants for therapeutic purpose is permitted as long as the International Normalized Ratio (INR) and/or a partial thromboplastin time (PTT) is within therapeutic limits (according to institution standards) within 7 days prior to initiation of study treatment and the patient has been on a stable dose of anticoagulants for \>= 2 weeks prior to initiation of study treatment. Prophylactic use of anticoagulants is allowed. However, the use of direct oral anticoagulant therapies such as dabigatran (Pradaxa \[registered trademark\]) and rivaroxaban (Xarelto \[registered trademark\]) may be used per PI discretion
Exclusion
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
What this trial measures
- Incidence of adverse eventsUp to 28 days after treatment
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 rateUp to 2 years from study enrollment
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 rateUp to 2 years from study enrollment
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)Time from study treatment initiation until disease progression or death, assessed up to 2 years from study enrollment
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.
- Overall survival (OS)From study treatment initiation until death from any cause, assessed up to 2 years from study enrollment
The Kaplan-Meier method will be used and the curves presented along with a 95% confidence interval on the median OS, separately by cohort.
- Duration of response (DOR)Length of time without disease progression or recurrence, up to 2 years from study enrollment
The Kaplan-Meier method will be used and the curves presented along with a 95% confidence interval on the median DOR, separately by cohort.
- Response to treatmentAssessed up to 2 years from study enrollment
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.