Triple Drug Therapy for Kidney Cancer
Recruiting in Palo Alto (17 mi)
+9 other locations
Overseen byRamaprasad Srinivasan
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: Immunosuppressants, Immunostimulants
Disqualifiers: Autoimmune disease, Active infection, Hypertension, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
Do I need to stop my current medications for the trial?
The trial protocol does not specify if you need to stop your current medications. However, you cannot have had any systemic therapy for kidney cancer within 4 weeks before starting the trial, and certain medications like herbal therapies must be stopped at least 1 week before. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drugs Atezolizumab, Tecentriq, Bevacizumab, Avastin, Erlotinib, and Tarceva for kidney cancer?
Bevacizumab, one of the drugs in the treatment, has shown effectiveness in improving progression-free survival in patients with metastatic renal cell carcinoma when combined with interferon, according to a phase 3 study.
12345Is the triple drug therapy for kidney cancer safe for humans?
The safety of the drugs Atezolizumab, Bevacizumab, and Erlotinib has been studied in various conditions. Bevacizumab, for example, has been approved for use in kidney cancer and is generally safe, but it can cause side effects like bleeding, high blood pressure, and blood clots. Managing these side effects is important to ensure patient safety and quality of life during treatment.
46789How is the triple drug therapy for kidney cancer unique?
The triple drug therapy for kidney cancer combines Atezolizumab, Bevacizumab, and Erlotinib, which is unique because it targets multiple pathways involved in cancer growth and spread, including the immune system, blood vessel formation, and cell growth signals, potentially offering a more comprehensive approach than single or dual therapies.
25101112Eligibility Criteria
This trial is for individuals aged 12 or older with advanced kidney cancer, including hereditary leiomyomatosis and renal cell carcinoma. Participants must have measurable disease, acceptable organ function, no more than two prior VEGF-targeted treatments, and no recent use of certain medications or therapies. Those with treated brain metastases stable for at least 3 months can join. Pregnant women and tobacco users who cannot quit are excluded.Inclusion Criteria
Your bilirubin levels need to be within a certain range, unless you have Gilbert's disease.
I can provide a tissue sample from my tumor or am willing to have a biopsy.
I have had 2 or fewer treatments targeting VEGF but no bevacizumab for my advanced cancer.
+15 more
Exclusion Criteria
I haven't had radiotherapy for kidney cancer in the last 2 weeks.
I haven't taken any immune-weakening medications in the last 2 weeks.
I have not had major surgery in the last 28 days.
+8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive bevacizumab, erlotinib, and atezolizumab in 21-day cycles
Up to 2 years
1 visit per cycle (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
Every 6 months
2 visits per year (in-person)
Participant Groups
The study tests a combination therapy using bevacizumab (stops blood vessels from feeding tumors), erlotinib (blocks proteins that signal cancer cells to multiply), and atezolizumab (boosts the immune system to fight cancer). The goal is to see if this trio can stabilize or shrink advanced-stage kidney cancers.
1Treatment groups
Experimental Treatment
Group I: Treatment (bevacizumab, atezolizumab, erlotinib)Experimental Treatment11 Interventions
Patients 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.
Atezolizumab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Tecentriq for:
- Melanoma
- Hepatocellular carcinoma
- Small cell lung cancer
- Non-small cell lung cancer
- Urothelial carcinoma
🇪🇺 Approved in European Union as Tecentriq for:
- Melanoma
- Hepatocellular carcinoma
- Small cell lung cancer
- Non-small cell lung cancer
- Urothelial carcinoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
National Cancer Institute LAOBethesda, MD
Ohio State University Comprehensive Cancer CenterColumbus, OH
Emory University Hospital MidtownAtlanta, GA
More Trial Locations
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Prediction of progression-free survival rates after bevacizumab plus interferon versus interferon alone in patients with metastatic renal cell carcinoma: comparison of a nomogram to the Motzer criteria. [2015]The combination of bevacizumab plus interferon (BEV+IFN) for treatment of metastatic renal cell carcinoma (mRCC) is associated with improved progression-free survival (PFS) in a phase 3 study.
New treatment approaches in renal cell carcinoma. [2021]Metastatic renal cell carcinoma (RCC) is notoriously chemoresistant; up until recently, immunotherapy (in particular interferon-alpha) has represented the treatment of choice. The understanding of the biology of RCC has resulted in the development of targeted therapies. In particular, multikinase inhibitors (sunitinib, sorafenib, axitinib, pazopanib), antivascular endothelial growth factor agents (bevacizumab), and mammalian target of rapamycin inhibitors (temsirolimus, everolimus) now have a role in the approach to different subsets of RCC. Sunitinib is indicated for the first-line therapy of metastatic RCC as a consequence of a positive phase III trial versus interferon-alpha; sorafenib is now registered for the second-line treatment of RCC, which was earlier treated with cytokine as a consequence of a positive phase III trial versus placebo. Bevacizumab is also indicated in the first-line treatment of metastatic RCC given in combination with interferon-alpha as a consequence of two positive phase III trials. Temsirolimus, unlike the other agents, has also shown activity in poor-prognosis patients, and is now the treatment of choice in previously untreated poor-prognosis RCC as a single agent. Everolimus can be considered as the best therapeutic option in patients with RCC pretreated with targeted agents as a consequence of a positive phase III study versus best supportive care. Markers for appropriate treatment selection, combined use of targeted agents, treatment of special histologies, and adjuvant and neoadjuvant setting represent important special issues to be dealt with in future studies.
Clinical management of metastatic kidney cancer: the role of new molecular drugs. [2021]Over the last few years, the most recent advances of the molecular mechanisms involved in renal cell carcinoma have led to the use of new drugs targeting VEGF, such as bevacizumab plus interferon, sorafenib, sunitinib, pazopanib, and axitinib, or the mTOR, such as temsirolimus and everolimus. The purpose of this review is to analyze the results of Phase III trial with these targeted agents, and on the management of the treatment and, in particular, when to start and to stop therapy and the use of alternative schedule of sunitinib. Recent developments in immunotherapy are also discussed.
Optimizing patient adherence to targeted therapies in renal cell carcinoma. [2014]The current standard of care for treating metastatic renal cell carcinoma is sequential therapy with vascular endothelial growth factor-targeted agents (i.e., axitinib, bevacizumab, pazopanib, sorafenib, and sunitinib) and mammalian target of rapamycin inhibitors (i.e., everolimus and temsirolimus). To maximize adherence to and persistence with targeted therapy, which should help improve clinical benefit, a clear understanding of the tolerability profiles of these agents and implementation of early, appropriately aggressive adverse event (AE) prevention and management strategies are key. Active and aggressive AE management should improve the quality of life of patients during the course of their treatment. Nurses are in a unique position to educate patients on the potential AEs they may experience and their prevention and management. This article reviews the safety and tolerability of currently available targeted therapies recommended for use in the second-line treatment setting, as well as their management in the context of maximizing clinical outcomes and patient quality of life.
Progress and contrasts of the development of tivozanib for therapy of kidney cancer. [2014]Targets for drug development for the treatment of kidney cancer (renal cell carcinoma; RCC) include vascular endothelial growth factor (VEGF) and its receptors and mammalian target of rapamycin. Currently available oral multitargeted VEGF tyrosine kinase inhibitors (TKIs) that have been approved by the US Food and Drug Administration for advanced RCC, include sunitinib, sorafenib and pazopanib. Off-target TKI inhibition can potentially preclude full-dose combination with other targeted and chemotherapeutic agents. There is a need to develop more potent and selective targeted agents for RCC therapy, which are more effective and have minimal off-target effects.
[Management of side effects associated with antiangiogenic treatment in renal cell carcinoma]. [2018]The recent development of antiangiogenic agents has revolutionized the management of renal cell carcinoma. In less than two-years, the French health authorities have approved the use of four drugs (sorafenib, sunitinib bevacizumab, temsirolimus) for the treatment of locally advanced or metastatic renal cell carcinoma. A fifth drug (everolimus) should be on the market some time. Clinicians have changed their practice and are faced with a number of new adverse events. The management of toxic effects is essential to ensure treatment compliance and patient quality of life. The present report describes in detail the adverse events associated with each therapeutic class and the management of side effects.
Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review. [2023]Tyrosine kinase inhibitors have been successfully developed in combination with immune checkpoint inhibitors to treat advanced renal cell carcinoma (RCC), further advancing treatment. While safety profiles are generally manageable with combination regimens, overlapping adverse events (AEs) and immune-related AEs can make treatment more complex. The CheckMate 9ER study evaluated the tyrosine kinase inhibitor cabozantinib in combination with the anti-programmed cell death protein-1 antibody nivolumab in patients with previously untreated advanced RCC. Cabozantinib + nivolumab demonstrated superiority over sunitinib for progression-free survival, overall survival, and objective response rate. These outcomes supported the approval of cabozantinib + nivolumab as a first-line therapy for advanced RCC. The safety profile was manageable with prophylaxis, supportive care, dose holds and reductions for cabozantinib, and dose holds and immunosuppressive therapy for nivolumab. This review discusses the safety results of CheckMate 9ER and provides guidance on managing some of the more clinically relevant AEs with a focus on overlapping AEs, including diarrhea, elevated amylase/lipase, hepatotoxicity, dermatologic reactions, fatigue, endocrine disorders, and nephrotoxicity. We discuss AE management strategies (prophylaxis, supportive care, dose modification, and immunosuppressive therapy), and provide recommendations for identifying the causative agent of overlapping AEs and for consulting specialists about organ-specific immune-related AEs. Optimizing AE management can maintain tolerability and should be a priority with cabozantinib + nivolumab treatment.
Analysis of Anti-Angiogenesis-Related Adverse Events Associated with Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitors (VEGFR-TKIs) in Patients with Metastatic Renal Cell Carcinoma. [2023]Limited studies have evaluated anti-angiogenesis-related adverse events involving oral vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) in metastatic renal cell carcinoma using real-world data.
FDA drug approval summary: bevacizumab plus interferon for advanced renal cell carcinoma. [2021]On July 31, 2009, the U.S. Food and Drug Administration granted approval for the use of bevacizumab (Avastin(R); Genentech, Inc., South San Francisco, CA) in combination with interferon (IFN)-alpha2a for the treatment of patients with metastatic renal cell carcinoma. The approval was primarily based on results from a randomized, double-blind, placebo-controlled clinical trial. The primary efficacy endpoint, progression-free survival (PFS), was assessed by investigators and by an independent review committee (IRC) blinded to treatment assignment. In total, 649 patients (bevacizumab plus IFN, 327; placebo plus IFN, 322) were enrolled. The median PFS times, by investigator determination, were 10.2 months for the bevacizumab plus IFN arm and 5.4 months for the placebo plus IFN arm (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.49-0.72; p /=3 adverse events were reported more frequently in bevacizumab-treated patients (31% versus 19% and 63% versus 47%, respectively). The most common bevacizumab-related toxicities were bleeding/hemorrhage, hypertension, proteinuria, and venous or arterial thromboembolic events.
Targeted therapies in metastatic renal cancer in 2009. [2018]The development of targeted molecules in renal carcinogenesis changed the therapeutic approaches of treatment for metastatic clear cell renal cell carcinoma. Four available drugs are currently available, i.e. bevacizumab, sunitinib, sorafenib and temsirolimus, but other molecules and combined therapy are under investigation. In this review we assess published reports of these targeted therapies and discuss the novel promising molecules targeting vascular endothelial growth factor and its receptors, the mammalian target of rapamycin and epithelial growth factor cascade.
Targeting growth factor and antiangiogenic pathways in clear-cell renal cell carcinoma: rationale and ongoing trials. [2019]Clear-cell renal cell carcinoma is characterized by the inactivation of the von Hippel-Lindau tumor suppressor gene, which results in an overproduction of vascular endothelial growth factor that promotes tumor angiogenesis, growth, and metastasis after binding with its receptor. The mammalian target of rapamycin signal transduction pathway is involved in the translation of hypoxia inducible factor-1 and vascular endothelial growth factor. Sunitinib, sorafenib, bevacizumab, and temsirolimus have improved clinical outcomes by inhibiting these tumorigenic pathways. Other multitargeted tyrosine kinase inhibitors (lapatinib, axitinib, pazopanib) and antiangiogenic agents (lenalidomide) have also demonstrated activity in early studies. Combinations of these agents are being evaluated. Clinical trials designed to further assess these and other agents need to be vigorously supported.
Update on the medical treatment of metastatic renal cell carcinoma. [2008]Metastatic renal cell carcinoma (mRCC) has long been treated only by immunotherapy with good results only in a small population of patients. In recent years, major improvements in treatment possibilities have occurred with the advent of anti-angiogenic drugs. In the past 2 yr, pivotal phase III trials have confirmed this major breakthrough by increasing the progression-free survival rates and/or overall survival rates provided by sunitinib, sorafenib, and bevacizumab, and more recently by the mTOR (mammalian target of rapamycin) inhibitors temsirolimus and everolimus.