Pazopanib for Renal Cell Carcinoma

Not currently recruiting at 701 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether pazopanib hydrochloride can help prevent the return of kidney cancer that has spread and been surgically removed. Pazopanib hydrochloride blocks enzymes and blood flow that tumors need to grow. Participants will receive either the drug or a placebo (inactive substance) to compare results. This trial suits individuals who have undergone kidney cancer surgery to remove all visible disease and currently show no signs of cancer. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that pazopanib hydrochloride is likely to be safe for humans?

Research has shown that pazopanib hydrochloride is generally well-tolerated by many patients. In a study involving patients with renal cell carcinoma (a type of kidney cancer), pazopanib delayed cancer growth or spread without causing major side effects. Specifically, the study noted that patients tolerated the treatment well.

While all treatments can have some side effects, this study suggests that pazopanib is generally safe for similar conditions. Prospective trial participants should discuss any concerns with a healthcare professional. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for renal cell carcinoma, which often includes treatments like sunitinib or sorafenib, pazopanib hydrochloride offers a unique approach. It works by targeting multiple pathways involved in tumor growth and blood supply, which may lead to better management of the cancer's progression. Researchers are excited about pazopanib because it has the potential to improve outcomes with a once-daily oral dose, making it a convenient option for patients. This treatment might offer an alternative with a distinct mechanism of action that could complement or even enhance current therapies.

What evidence suggests that pazopanib hydrochloride might be an effective treatment for kidney cancer?

Research shows that pazopanib hydrochloride can help treat metastatic renal cell carcinoma (mRCC). In one study, about 29% of patients responded positively to the treatment. Another study found that 5.1% of patients had a complete response, 22% had a partial response, and 35.6% had stable disease, meaning their cancer did not worsen. Pazopanib has also improved progression-free survival, helping to delay cancer progression. In this trial, participants will receive either pazopanib or a placebo to further evaluate its effectiveness. Overall, these findings support the potential of pazopanib for treating advanced kidney cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Leonard J Appleman

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40425323/

Efficacy and Treatment Outcomes of First-line Pazopanib ... Best overall response was complete response in 5.1% (3/59 patients), partial response in 22% (13/59 patients), and stable disease in 35.6% (21/59 patients).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9177258/

Real-world data on the efficacy and safety of pazopanib in ... In addition, the results of our analysis revealed that the response rate of pazopanib was 29% when treating mRCC, and that the response rate was ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149291812000197

Pazopanib for the Treatment of Metastatic Renal Cell ... The only Phase III trial of pazopanib suggests improvement of progression-free survival in RCC as well as tolerability in the selected population. Introduction.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.6_suppl.696

Phase II efficacy trial of pazopanib in nonclear cell ... The primary endpoint was overall survival rate at 12 months. Secondary endpoints were best tumor response rates after two cycles, PFS, OS and ...

5. ar.iiarjournals.org ar.iiarjournals.org/content/45/6/2527

Efficacy and Treatment Outcomes of First-line Pazopanib ... Median progression-free survival was 17.7 (95% CI=9.15-26.25) months and declined with the International Metastatic Renal Cell Carcinoma Database Consortium ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00334282

Study Details | NCT00334282 | Safety and Efficacy of ... To evaluate efficacy and safety of pazopanib compared to placebo in patients with locally advanced and/ or metastatic renal cell carcinoma (RCC).

7. journals.lww.com journals.lww.com/ursc/fulltext/2021/32030/outcomes_of_starting_low_dose_pazopanib_in.4.aspx

Outcomes of Starting Low-dose Pazopanib in Patients with... Partial response was seen in 5 patients (27.8%) and stable disease in 10 patients (55.6%); median progression-free survival was 11.9 months (95% confidence ...