Pazopanib + Bevacizumab for Kidney Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two drugs, pazopanib and bevacizumab, can work together to treat kidney cancer that has spread. The main goal is to determine the best dose, understand any side effects, and assess how well these drugs can stop tumor growth. Pazopanib may block enzymes that help tumors grow and cut off their blood supply, while bevacizumab (also known as Avastin) might prevent tumors from spreading. Individuals with biopsy-confirmed kidney cancer who have not yet received treatment for their metastatic cancer might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to contribute to groundbreaking research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining pazopanib hydrochloride and bevacizumab may help treat advanced kidney cancer. Studies have found that this combination can significantly extend progression-free survival, the time patients live without their cancer worsening.

Researchers have studied this combination to determine the best dose and monitor side effects. Previous studies suggest that pazopanib alone is generally well-tolerated, though it can cause side effects like diarrhea, high blood pressure, and liver issues. Bevacizumab can also lead to high blood pressure and bleeding problems.

While these treatments carry some risks, the studies aim to balance effective cancer treatment with side effect management. The current trial seeks to confirm these findings and better understand the safety and optimal dose levels when these drugs are used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for kidney cancer, which often involves drugs like sunitinib or everolimus, the combination of pazopanib hydrochloride and bevacizumab offers a unique approach. These treatments work by targeting and inhibiting specific pathways that cancer cells use to grow and spread. Pazopanib hydrochloride is a tyrosine kinase inhibitor that blocks proteins responsible for tumor growth, while bevacizumab is a monoclonal antibody that prevents the formation of new blood vessels that supply the tumor. Researchers are excited about this combination because it tackles the cancer on two fronts, potentially leading to more effective control of the disease.

What evidence suggests that pazopanib hydrochloride and bevacizumab might be effective for kidney cancer?

Research has shown that using pazopanib and bevacizumab together, as studied in this trial, may help treat kidney cancer that has spread. One study found that more than half of the patients with advanced kidney cancer responded well to this treatment, with many continuing it for almost four months. Specifically, over 50% of the patients had a positive response, and 43% saw their disease stabilize. This suggests the treatment might help slow down or stop the cancer from growing by blocking the enzymes and blood flow that tumors need to grow. These findings indicate it could be a good option for patients with metastatic kidney cancer. ^{3 4 6 7 8}

Who Is on the Research Team?

Saby George

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. urologytimes.com urologytimes.com/view/pazopanib-plus-bevacizumab-shows-promising-phase-2-efficacy-in-ccrcc

Pazopanib plus bevacizumab shows promising phase 2 ... The encouraging results suggest that alternating pazopanib with bevacizumab is a promising treatment regimen for renal cell carcinoma patients ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3763778/

The prospects of pazopanib in advanced renal cell ... The RR in the overall study population was 30%, with a median duration of response of 58.7 weeks, with similar rates seen in the treatment-naive (32%) and ...

3. withpower.com withpower.com/trial/pazopanib-bevacizumab-for-kidney-cancer-8021c

Pazopanib + Bevacizumab for Kidney Cancer 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 ...

4. actionkidneycancer.org actionkidneycancer.org/pazopanib-plus-bevacizumab-shows-promise-as-a-first-line-treatment-for-kidney-cancer/

Pazopanib plus bevacizumab shows promise as a first-line ... More than half of the patients (55%) responded to treatment and more than 4 in 10 patients (43%) had stable disease, a clinical response rate of ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7278098/

Pazopanib as a possible option for the treatment of metastatic ... The specific outcomes of nccRCC patients were reported by four studies. Pazopanib alone as first-line treatment gave overall response rates ranging from 27% to ...

6. trial.medpath.com trial.medpath.com/news/89dc17d1f31da15a/combo-treatment-doubles-survival-for-patients-with-advanced-kidney-cancer

Pazopanib and Bevacizumab Combination Doubles Survival in ... A phase 2 clinical trial demonstrated that combining pazopanib and bevacizumab significantly extends progression-free survival in patients with advanced kidney ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3235998/

Pharmacotherapy Options in Advanced Renal Cell ... This article will review the evidence for pazopanib in various settings of treatment for patients with advanced RCC, develop evidence-based treatment algorithms ...

8. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/kidney-cancer

Kidney Cancer Clinical Trials This randomized phase III trial studies how well pazopanib hydrochloride works compared to placebo in treating patients with metastatic kidney cancer who have ...