Pazopanib + Bevacizumab for Kidney Cancer

Recruiting at 4 trial locations

Overseen By Deepak Kilari, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Roswell Park Cancer Institute

Must not be taking: Anticoagulants, Anti-cancer drugs

Disqualifiers: Brain metastases, Recent cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 70 days per course

51 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that you cannot be on another anti-cancer drug or anti-coagulation therapy. If you are on these, you may need to stop them to participate.

What data supports the effectiveness of the drug Pazopanib for kidney cancer?

Pazopanib has been shown to improve outcomes in patients with advanced kidney cancer by extending the time before the disease worsens by about 5 months compared to a placebo. However, it comes with significant side effects, and its overall survival benefit is still unclear. ^{1 2 3 4 5}

What safety information is available for the combination of Pazopanib and Bevacizumab in treating kidney cancer?

Pazopanib, used for kidney cancer, can cause side effects like nausea, liver problems, high blood pressure, and heart issues. Bevacizumab, often used in combination, may have similar risks. It's important to manage these side effects early to improve treatment outcomes. ^{5 6 7 8 9}

How does the drug combination of Pazopanib and Bevacizumab differ from other treatments for kidney cancer?

The combination of Pazopanib and Bevacizumab is unique because it targets multiple pathways involved in tumor growth and blood vessel formation, specifically inhibiting tyrosine kinases and VEGF receptors, which are crucial for angiogenesis (the formation of new blood vessels). This approach is different from traditional chemotherapy and offers a novel mechanism of action compared to standard treatments like interferon alfa. ^{1 2 5 10 11}

What is the purpose of this trial?

This phase I/II trial studies the side effects and best dose of pazopanib hydrochloride and bevacizumab and to see how well they work in treating patients with previously untreated kidney cancer that has spread to other places in the body (metastatic). Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Pazopanib hydrochloride may also stop the growth of tumor cells by blocking blood flow to the tumor. Monoclonal antibodies, such as bevacizumab, can prevent tumor growth by blocking the ability of tumor cells to grow and spread. Giving pazopanib hydrochloride together with bevacizumab may kill more tumor cells.

Research Team

Saby George

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

This trial is for adults with clear cell renal cell carcinoma that has spread, who are in good physical condition (ECOG <=1), have not had certain other cancers or major surgeries recently, and do not have brain metastases or serious cardiovascular conditions. They must be able to take oral medication and agree to use birth control if of childbearing potential.

Inclusion Criteria

Hemoglobin >= 10 gm/dL

Total bilirubin =< upper limit of normal (ULN)

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< ULN

Exclusion Criteria

I do not have any ongoing illnesses that would stop me from following the study's requirements.

History of any of the following cardio-vascular condition: Myocardial infarction (MI), Unstable angina, Coronary artery bypass grafting (CABG)-unless patient had a negative stress test within 6 months of screening, Coronary angioplasty or stenting, Symptomatic peripheral arterial disease (PAD), History of symptomatic chronic congestive heart failure (CHF), History of cerebrovascular accidents including transient ischemic attacks (TIA), Corrected QT interval (QTc) > 480 msec, Uncontrolled hypertension (systolic blood pressure [BP] > 150 mm Hg or diastolic BP of > 90 mm Hg); if the screening BP is elevated, adjustments in anti-hypertensives are permitted and a re-screening will be permitted for BP assessment with three consecutive values obtained 2 minutes apart; the 3 values have to be below 150/90 mm Hg for eligibility and can only be obtained after 2 days of the last change in anti-hypertensive medication; use of clonidine is not permissible for adjusting the BP during this period, History of deep vein thrombosis (DVT) or pulmonary embolism (PE) in the past 6 months, Subjects should not have packed red blood cells (PRBC) or platelet transfusion within 14 days of the screening, Evidence of active bleeding or bleeding disorder, Subjects currently on anti-coagulation therapy are not eligible, Unable to discontinue the use of prohibited medications, Pregnant or nursing female subjects, Unwilling or unable to follow protocol requirements, Any condition which in the investigator's opinion deems the subject an unsuitable candidate to receive study drug, Received an investigational agent within 30 days prior to enrollment

Concurrent use of another anti-cancer drug including an investigational anti-cancer agent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pazopanib hydrochloride orally on days 1-28 and bevacizumab intravenously on days 36 and 50. Courses repeat every 70 days in the absence of disease progression or unacceptable toxicity.

70 days per course

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and Phase II patients followed by telephone every 12 months.

Up to 12 months

Treatment Details

Interventions

• Bevacizumab
• Pazopanib Hydrochloride

Trial Overview The study is testing the combination of Pazopanib Hydrochloride, a drug that may block tumor growth by inhibiting enzymes and blood flow to the tumor, with Bevacizumab, an antibody that can prevent tumors from growing. The phase I/II trial aims to determine the best dose and how well these drugs work together against metastatic kidney cancer.

Participant Groups

Group I: Treatment (pazopanib hydrochloride and bevacizumab) Experimental Treatment 4 Interventions

Patients receive pazopanib hydrochloride PO on days 1-28 and bevacizumab IV over 30-90 minutes on days 36 and 50. Courses repeat every 70 days in the absence of disease progression or unacceptable toxicity.

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Findings from Research

In a study of 143 patients with advanced renal cell carcinoma (RCC), over 50% of patients remained on pazopanib therapy for nearly 4 months, demonstrating high persistence and compliance across both treatment-naïve and previously treated groups.

Younger age and higher comorbidity were identified as strong predictors of better persistence and compliance with pazopanib treatment, suggesting that these factors may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistence and compliance with pazopanib in patients with advanced renal cell carcinoma within a U.S. administrative claims database. Hackshaw, MD., Nagar, SP., Parks, DC., et al.[2023]

Pazopanib, a drug that inhibits multiple receptor tyrosine kinases, showed a median progression-free survival of 9.2 months in patients with advanced renal carcinoma, compared to 4.2 months with placebo, based on a trial involving 435 patients.

Despite its efficacy in delaying disease progression, pazopanib has a concerning adverse effect profile, including serious cardiovascular and gastrointestinal issues, leading to a current unfavorable risk-benefit balance for its use in advanced kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib. Kidney cancer: many risks, but is there a benefit for patients? [2021]

A comprehensive pharmaceutical intervention for 37 outpatients receiving pazopanib for renal cell carcinoma significantly reduced the incidence of grade 2 or more nausea (3% vs. 38%) and anorexia (8% vs. 46%) compared to a control group of 13 patients, indicating improved management of adverse events.

The intervention also led to increased adherence to treatment and a longer median time to treatment failure (10.2 months vs. 1.7 months), suggesting that early management of side effects can enhance overall treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usefulness of Implementing Comprehensive Pharmaceutical Care for Metastatic Renal Cell Carcinoma Outpatients Treated with Pazopanib. Todo, M., Shirotake, S., Nishimoto, K., et al.[2021]

A review of seven targeted cancer therapies (sunitinib, pazopanib, bevacizumab, temsirolimus, axitinib, everolimus, and sorafenib) revealed that all these medications are associated with adverse events, highlighting the importance of monitoring patients closely.

Effective management strategies for these side effects can prevent them from becoming severe, which is crucial to maintaining the full efficacy of the treatments and avoiding unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A contemporary update on rates and management of toxicities of targeted therapies for metastatic renal cell carcinoma. Alasker, A., Meskawi, M., Sun, M., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Persistence and compliance with pazopanib in patients with advanced renal cell carcinoma within a U.S. administrative claims database. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Pazopanib for the treatment of renal cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Is change in blood pressure a biomarker of pazopanib and sunitinib efficacy in advanced/metastatic renal cell carcinoma? [2022]

4. England pubmed.ncbi.nlm.nih.gov

Relationships between pazopanib exposure and clinical safety and efficacy in patients with advanced renal cell carcinoma. [2021]

5. France pubmed.ncbi.nlm.nih.gov

Pazopanib. Kidney cancer: many risks, but is there a benefit for patients? [2021]

6. Greece pubmed.ncbi.nlm.nih.gov

Usefulness of Implementing Comprehensive Pharmaceutical Care for Metastatic Renal Cell Carcinoma Outpatients Treated with Pazopanib. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Pazopanib and Statin-Induced Rhabdomyolysis. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

A contemporary update on rates and management of toxicities of targeted therapies for metastatic renal cell carcinoma. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Pazopanib: an oral multitargeted tyrosine kinase inhibitor for use in renal cell carcinoma. [2021]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Pazopanib: in advanced renal cell carcinoma. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Pazopanib: a multikinase inhibitor with activity in advanced renal cell carcinoma. [2021]