Pazopanib for Advanced or Refractory Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: QTc prolongation, CYP3A4 inhibitors

Disqualifiers: Cardiovascular conditions, Brain metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 1 year

54 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and the best dose of pazopanib hydrochloride in treating patients with solid tumors that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or does not respond to treatment (refractory). Pazopanib hydrochloride may prevent the growth of new blood vessels that tumors need to grow. Studying samples of blood in the laboratory from patients receiving pazopanib hydrochloride may help doctors learn more about the effects of the body on the drug. It may also help doctors understand how well patients respond to treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as those with a risk of heart rhythm problems (QTc prolongation) and some that affect liver enzymes (CYP3A4 inhibitors and inducers). If you're on these medications, you may need to switch to alternatives before joining the trial.

What data supports the effectiveness of the drug Pazopanib Hydrochloride for advanced or refractory cancer?

Pazopanib has shown effectiveness in treating advanced renal cell carcinoma (a type of kidney cancer) as demonstrated in studies from various regions, including the U.S. and Latin America, where it is used as a targeted therapy. ^{1 2 3 4 5}

What safety information is available for pazopanib in humans?

Pazopanib has been associated with several side effects, including liver issues, nausea, vomiting, diarrhea, high blood pressure, and fatigue. It is important to monitor liver function during treatment due to potential liver damage. Other side effects can include changes in hair color, loss of appetite, and changes in taste. ^{6 7 8 9 10}

How is the drug pazopanib unique for treating advanced or refractory cancer?

Pazopanib is unique because it is an oral medication that targets multiple proteins involved in tumor growth, specifically in advanced renal cell carcinoma and soft tissue sarcoma. It works by inhibiting tyrosine kinases, which are enzymes that promote cancer cell growth, and has shown to significantly extend the time patients live without their cancer worsening. ^{2 11 12 13 14}

Research Team

Keith C Bible

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for patients with advanced or treatment-resistant solid tumors. Eligible participants must have normal organ function, measurable disease, no severe heart conditions or blood clots in the past 6 months, and a life expectancy of at least 3 months. They should not be pregnant or nursing and must agree to use contraception.

Inclusion Criteria

My blood clotting time is near normal and I'm not on warfarin.

My blood clotting time is within normal limits and I'm not on warfarin.

My cancer cannot be treated with surgery or other standard treatments.

Exclusion Criteria

I don't have stomach ulcers, bowel diseases, or recent severe stomach/intestine issues.

You are currently experiencing a serious wound, ulcer, bone fracture, or bleeding disorder. You have a history of abnormal bleeding or hemoptysis (coughing up blood) within the past 8 weeks. You have poorly controlled depression or anxiety, or have had suicidal thoughts within the past 6 months. You are taking warfarin, but not low molecular weight heparin. You are HIV-positive and receiving combination antiretroviral therapy.

My heart's electrical cycle is longer than normal or I'm on medication that can extend it.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pazopanib hydrochloride orally once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course length can be extended to 56 days after 12 courses (1 year) of treatment.

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

3 months

Treatment Details

Interventions

• Pazopanib Hydrochloride

Trial Overview The study is testing Pazopanib Hydrochloride's effectiveness on preventing tumor growth by inhibiting new blood vessel formation. It involves determining the best dose while monitoring side effects and how the body processes the drug through blood sample analysis.

Participant Groups

Group I: Treatment (pazopanib hydrochloride) Experimental Treatment 3 Interventions

Patients receive pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course length can be extended to 56 days at the discretion of the treating physician after 12 courses (1 year) of treatment on 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]

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. England pubmed.ncbi.nlm.nih.gov

Prospective observational study on Pazopanib in patients treated for advanced or metastatic renal cell carcinoma in countries in Asia Pacific, North Africa, and Middle East regions: PARACHUTE study. [2021]

2. 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]

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

A Phase I, Dose-Escalation Trial of Pazopanib in Combination with Cisplatin in Patients with Advanced Solid Tumors: A UNICANCER Study. [2022]

4. 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]

5. Germany pubmed.ncbi.nlm.nih.gov

Pazopanib pharmacokinetically guided dose optimization in three cancer patients with gastrointestinal resection. [2023]

6. 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]

7. Greece pubmed.ncbi.nlm.nih.gov

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

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

Pazopanib and Statin-Induced Rhabdomyolysis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Occurrence of abscesses during treatment with pazopanib in metastatic renal cancer: a case report. [2021]

10. 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]

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

Pazopanib: in advanced renal cell carcinoma. [2021]

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

Incorporation of pazopanib in maintenance therapy of ovarian cancer. [2022]

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

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

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]