Pazopanib for Renal Cell Carcinoma

Recruiting at 683 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, QTc prolonging drugs

Disqualifiers: Peptic ulcer, Heart failure, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 12 months

129 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you cannot take strong CYP3A4 inhibitors or drugs that prolong the QTc interval. If you're on these medications, you should stop them at least 5 half-lives before starting the trial.

What data supports the effectiveness of the drug Pazopanib Hydrochloride for treating renal cell carcinoma?

Research shows that Pazopanib, a drug used for kidney cancer, has been effective in prolonging the time patients live without the disease getting worse. It is approved as a first treatment option for advanced kidney cancer and has shown good results in real-world settings. ^{1 2 3 4 5}

What safety information is available for pazopanib in humans?

Pazopanib, used for treating renal cell carcinoma, can cause side effects like nausea, liver issues, diarrhea, high blood pressure, and mouth sores. It has a warning for liver toxicity, so regular liver monitoring is important. Other common side effects include changes in hair color, fatigue, and stomach pain. ^{2 6 7 8 9}

How does the drug pazopanib differ from other treatments for renal cell carcinoma?

Pazopanib is unique because it is an oral medication that targets multiple pathways involved in tumor growth, specifically inhibiting angiogenesis (the formation of new blood vessels that tumors need to grow) by blocking receptors like VEGFR. Unlike traditional chemotherapy, which has limited impact on renal carcinoma, pazopanib has shown to significantly extend progression-free survival in patients with advanced renal cell carcinoma. ^{10 11 12 13 14}

What is the purpose of this trial?

This trial is testing whether pazopanib hydrochloride can help prevent the return of kidney cancer in patients who have had surgery to remove it. The medication aims to stop cancer cell growth and block blood flow to tumors. Patients will take the drug for several months and be monitored frequently. Pazopanib has been approved for treating kidney cancer since 2009.

Research Team

Leonard J Appleman

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for patients with metastatic kidney cancer who've had surgery to remove all detectable disease. They should be in good physical condition, able to swallow pills without gastrointestinal issues, and have no remaining signs of cancer on scans. Women must not be pregnant and participants need effective contraception.

Inclusion Criteria

My heart's electrical activity, measured by ECG, is within a safe range.

My kidney cancer is confirmed and has spread, but it's not purely papillary or chromophobe type.

I have confirmed I am not pregnant through a test within the last 2 weeks.

Exclusion Criteria

My cancer is located only in my kidneys, with no spread to other parts of my body.

I have stopped taking any medication that affects my heart's rhythm for a specific period before joining the study.

I have received or am receiving treatment for kidney cancer; a placebo in a previous trial is okay.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pazopanib hydrochloride or placebo orally once daily for up to 13 courses, with each course lasting 28 days

12 months

Monthly visits for treatment and imaging

Follow-up

Participants are monitored for disease recurrence and overall survival

10 years

Every 3 months for the first 2 years, every 6 months for the next 3 years, then annually

Treatment Details

Interventions

• Pazopanib Hydrochloride

Trial Overview The study compares pazopanib hydrochloride, a drug that may prevent tumor growth by blocking enzymes and blood flow to tumors, against a placebo. It's randomized: patients are put into the treatment or placebo group by chance.

Participant Groups

Group I: Arm A (Pazopanib) Experimental Treatment 4 Interventions

Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout the study.

Group II: Arm B (Placebo) Placebo Group 4 Interventions

Patients receive placebo PO QD on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout the study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

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]

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]

Pazopanib, an antineoplastic agent approved by the European Commission for advanced renal cell carcinoma, significantly increases progression-free survival, with a median of 9.2 months compared to 4.2 months for placebo in the pivotal trial VEG105192.

Common side effects of pazopanib include diarrhea, hypertension, and fatigue, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency review of pazopanib for the treatment of advanced renal cell carcinoma: summary of the scientific assessment of the Committee for Medicinal Products for Human Use. Nieto, M., Borregaard, J., Ersbøll, J., et al.[2021]

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]

Pazopanib significantly improved progression-free survival (PFS) in patients with advanced renal cell carcinoma (RCC), with a median PFS of 9.2 months compared to 4.2 months for placebo, indicating its efficacy as a treatment option.

The objective response rate was notably higher with pazopanib at 30% versus only 3% for placebo, and the treatment was generally well-tolerated, with no major differences in quality of life reported between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial. Sternberg, CN., Davis, ID., Mardiak, J., et al.[2023]

A dried blood spot (DBS) assay was successfully developed and validated for monitoring pazopanib levels, providing a patient-friendly method for therapeutic drug monitoring.

The assay showed a strong correlation with plasma concentrations, indicating it can effectively guide treatment to ensure patients reach the beneficial plasma trough concentration of ≥20.5 μg/ml.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and clinical validation of an LC-MS/MS method for the quantification of pazopanib in DBS. Verheijen, RB., Bins, S., Thijssen, B., et al.[2021]

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

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

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

Real-World Effectiveness and Tolerability of Pazopanib as First Targeted Therapy in Metastatic Renal Cell Carcinoma: A Retrospective Chart Review in Latin America. [2021]

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

Pazopanib: Evidence review and clinical practice in the management of advanced renal cell carcinoma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Health-related quality of life in patients with advanced renal cell carcinoma receiving pazopanib or placebo in a randomised phase III trial. [2022]

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

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

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

Prescriber Compliance With Liver Monitoring Guidelines for Pazopanib in the Postapproval Setting: Results From a Distributed Research Network. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Pazopanib and Statin-Induced Rhabdomyolysis. [2022]

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

The European Medicines Agency review of pazopanib for the treatment of advanced renal cell carcinoma: summary of the scientific assessment of the Committee for Medicinal Products for Human Use. [2021]

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

Pazopanib: in advanced renal cell carcinoma. [2021]

11. France pubmed.ncbi.nlm.nih.gov

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

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

First-Line PAzopanib in NOn-clear-cell Renal cArcinoMA: The Italian Retrospective Multicenter PANORAMA Study. [2021]

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

Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial. [2023]

14. England pubmed.ncbi.nlm.nih.gov

Development and clinical validation of an LC-MS/MS method for the quantification of pazopanib in DBS. [2021]