Combining three medications for advanced kidney cancer treatment
Official title: 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
Run by National Cancer Institute (NCI) · NCT04981509 · Data updated 2026-11-12
This study is testing a combination of three medications to see if they can help people with advanced kidney cancer feel better and live longer.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Ages | 12 Years and up |
| Sex | All |
| Enrollment | 65 (estimated) |
| Sponsor | National Cancer Institute (NCI) NIH |
| Drugs / interventions | bevacizumab, atezolizumab, radiation, methotrexate, cyclophosphamide, prednisone, erlotinib, Immunotherapy |
| Locations | 13 sites (La Jolla, California and 12 other locations) |
| Status | Recruiting |
| Started | June 10, 2022 |
| Main results expected | December 31, 2027 |
| Study ends | December 31, 2027 |
| Registry record updated | October 28, 2026 |
| Trial ID | NCT04981509 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates include patients diagnosed with advanced hereditary leiomyomatosis and renal cell carcinoma or advanced sporadic/non-HLRCC papillary renal cell carcinoma.
✕Probably not a fit
Patients who have previously received bevacizumab therapy in the metastatic setting or those with prior treatment using PD-1 or PD-L1 inhibitors may not benefit from this study.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This phase II trial evaluates the effects of a combination therapy using bevacizumab, erlotinib, and atezolizumab in patients with advanced hereditary leiomyomatosis and renal cell carcinoma. The study aims to assess the complete response rate, safety, and tolerability of the treatment, as well as secondary outcomes such as progression-free survival and overall survival. Participants will undergo various assessments, including immune response evaluations and tumor tissue analysis, to understand the treatment's impact on cancer progression.
Why it matters
Potential benefit: If successful, this combination therapy could provide a new effective treatment option for patients with advanced kidney cancer.
How similar studies have gone: While combination therapies in cancer treatment have shown promise, this specific combination is novel and has not been extensively tested in prior studies.
Who can join: the full rules
Show full inclusion / exclusion criteria
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 it's running
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Emory University Hospital Midtown
Atlanta, Georgia, United States Recruiting -
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States Recruiting -
Emory Saint Joseph's Hospital
Atlanta, Georgia, United States Recruiting -
NCI - Center for Cancer Research
Bethesda, Maryland, United States Recruiting -
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States Recruiting -
UT MD Anderson Cancer Center
Houston, Texas, United States Recruiting
Show 7 more locations
-
UC San Diego Moores Cancer Center
La Jolla, California, United States Suspended -
Northwestern University
Chicago, Illinois, United States Suspended -
National Institutes of Health Clinical Center
Bethesda, Maryland, United States Suspended -
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States Suspended -
NYU Langone Hospital - Long Island
Mineola, New York, United States Active not recruiting -
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States Active not recruiting -
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States Suspended
Study contacts
- Principal investigator: Ramaprasad Srinivasan — National Cancer Institute LAO
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.