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NCT04981509 · National Cancer Institute (NCI)

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

What this study is about

This phase II trial studies the effects of two or more treatments used together 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.

View original scientific description

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.

Interventions

BIOLOGICAL

Atezolizumab

Given PO

BIOLOGICAL

Bevacizumab

Given IV

PROCEDURE

Biopsy Procedure

Undergo biopsy

PROCEDURE

Biospecimen Collection

Undergo blood collection

PROCEDURE

Bone Scan

Undergo bone scan

PROCEDURE

Computed Tomography

Undergo CT without contrast

PROCEDURE

Computed Tomography with Contrast

Undergo CT with contrast

DRUG

Erlotinib

Given PO

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

PROCEDURE

Positron Emission Tomography

Undergo PET

DRUG

Sodium Fluoride F-18

Given F-18 sodium fluoride

Primary outcome measures

Incidence of adverse events

Time frame: Up 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 rate

Time frame: Up 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 rate

Time frame: Up 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 frame: 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)

Time frame: 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)

Time frame: 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 treatment

Time frame: Assessed 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.

Who can participate

This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.

Inclusion criteria

  • 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)

Exclusion criteria

  • 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
  • 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

Where

  • La Jolla, California
  • Atlanta, Georgia
  • Chicago, Illinois
  • Bethesda, Maryland
  • New Brunswick, New Jersey
  • Mineola, New York
  • New York, New York
  • Columbus, Ohio
  • Pittsburgh, Pennsylvania
  • Houston, Texas

Related conditions & keywords

Hereditary Leiomyomatosis and Renal Cell CarcinomaPapillary Renal Cell CarcinomaRenal Cell CarcinomaSporadic Papillary Renal Cell CarcinomaStage III Renal Cell Cancer AJCC v8Stage IV Renal Cell Cancer AJCC v8

Frequently asked questions

What is a clinical trial?

A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.

Is it safe to participate?

Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.

Will I be compensated?

Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.

Will I receive a placebo instead of treatment?

When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.

Can I leave a trial if I change my mind?

Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.

How long does a clinical trial last?

Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.

Data: ClinicalTrials.gov · synced Sep 29, 2026 · Source of record for eligibility and locations

📊
1 of 65 participants interested
2% interest

See if this study fits

A short prescreen based on this study's listed criteria. A coordinator confirms eligibility — this is not a medical assessment.

Preparing your pre-screening questions…

Study locations

Choose your preferred location, or select flexible during enrollment.

SUSPENDED

La Jolla

California

Location available
RECRUITING

Atlanta

Georgia

Location available
RECRUITING

Atlanta

Georgia

Location available
RECRUITING

Atlanta

Georgia

Location available
SUSPENDED

Chicago

Illinois

Location available
SUSPENDED

Bethesda

Maryland

Location available
RECRUITING

Bethesda

Maryland

Location available
SUSPENDED

New Brunswick

New Jersey

Location available
ACTIVE_NOT_RECRUITING

Mineola

New York

Location available

And 4 more locations available.

Express your interest

Share your contact details and a study coordinator can follow up about screening.

Secure & Confidential

Your information is protected and will only be shared with the research team.

What participation can include

  • Study-related care provided by the research team
  • Close monitoring by medical professionals
  • Possible compensation for time and travel*
  • The option to withdraw at any time
  • Contributing to medical research that may help future patients

*Compensation varies by study. Confirm details with coordinator.

Typical next steps

  1. 1.Submit this form
  2. 2.Phone screening
  3. 3.In-person assessment if eligible
  4. 4.Begin participation

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Looking for Kidney Cancer Treatment in La Jolla?

Join others in California exploring innovative treatment options through clinical research

Kidney Cancer Treatment Options in La Jolla, California

If you're searching for Kidney Cancer treatment in La Jolla, participating in a clinical research study may provide access to innovative approaches under expert medical supervision. This study is actively recruiting participants in La Jolla, Atlanta, Chicago and surrounding areas.

Clinical trials offer participants the opportunity to receive cutting-edge treatments while contributing to medical research that may help future patients with Kidney Cancer. All study-related care is provided at no cost to participants.

Local Sites
3 locations in California
Now Enrolling
Up to 65 participants
Quick Start
Screening available now

Why Consider a Clinical Trial for Kidney Cancer?

Potential Benefits

  • ✓Access to new treatment approaches before public availability
  • ✓Close monitoring by experienced medical professionals
  • ✓Study-related care provided at no cost
  • ✓Contribute to medical research for Kidney Cancer

What to Expect

  • →Initial screening to determine eligibility
  • →Regular check-ups and monitoring visits
  • →Possible compensation for time and travel
  • →You can withdraw at any time

Frequently Asked Questions About This Kidney Cancer Study

Important Clinical Trial Information

This information is provided for educational purposes and does not constitute medical advice. Clinical trial participation involves potential risks and benefits. Eligibility requirements apply and will be assessed during the screening process.

Study identifier: NCT04981509. For complete study details, visit ClinicalTrials.gov. Always consult with your healthcare provider before making decisions about your medical care or participating in clinical research.