Pazopanib for Advanced or Refractory Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects and optimal dose of pazopanib hydrochloride for individuals with advanced or stubborn cancers that have spread and resist other treatments. The drug may help by blocking the growth of new blood vessels that tumors need to grow. Participants must provide blood samples to help researchers understand how the drug works in the body. This trial could suit those with solid tumors that other treatments can't control and who are willing to visit the Mayo Clinic for follow-ups. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new 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.

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

Research shows that pazopanib hydrochloride is generally well tolerated by patients with advanced cancer. In earlier studies, some patients experienced side effects like increased liver enzymes and bilirubin, which can affect liver function. However, these side effects were not common for everyone. Serious liver problems were rare but did occur in a few cases.

Most patients in the studies handled the treatment without major issues. When used alone, pazopanib showed promise in slowing tumor growth in various types of cancer. The usual effective and manageable dose was 800 mg once a day, providing insight into how the body responds to the drug.

Overall, pazopanib has potential as a treatment option, with side effects that many patients can manage. Prospective trial participants should consult their healthcare provider to understand what this might mean for them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced or refractory cancer, which often involve chemotherapy or targeted therapies with well-known pathways, pazopanib hydrochloride works by specifically inhibiting multiple tyrosine kinases. This unique mechanism targets the growth of new blood vessels that tumors need to thrive, potentially slowing or stopping the progression of cancer. Researchers are excited about pazopanib because it offers a different approach with the possibility of being effective in patients who have not responded to existing treatments. Additionally, it is administered orally, which can be more convenient and less invasive than traditional intravenous therapies.

What evidence suggests that pazopanib hydrochloride might be an effective treatment for advanced or refractory cancer?

Research has shown that pazopanib hydrochloride, the treatment under study in this trial, may help treat advanced cancers. In one study, about 5% of patients experienced complete cancer remission, 22% saw tumor reduction, and 36% had stable disease. Another study found that patients with advanced kidney cancer lived for about 19.4 months on average. Real-world data also suggest that pazopanib is effective and generally well-tolerated, with 93% of patients surviving at least 6 months and 89% surviving at least 12 months after starting treatment. These findings suggest that pazopanib could be a helpful option for patients with advanced or hard-to-treat cancers. ^{4 6 7 8 9}

Who Is on the Research Team?

Keith C Bible

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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.

I can swallow and absorb pills without any issues.

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 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8414075/

Real-World Outcome and Prognostic Factors of Pazopanib ... Pazopanib was found to be tolerable and effective, with outcomes comparable to those reported in clinical trials and real-world data.

2. 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).

3. sciencedirect.com sciencedirect.com/science/article/pii/S1558767322001367

A Study of Pazopanib Safety and Efficacy in Patients With ... Pazopanib is tolerated and effective in advanced RCC patients who are performance status ECOG 2. •. Pazo2 reports a median overall survival of 19.4 months (95% ...

4. actionkidneycancer.org actionkidneycancer.org/real-world-use-of-pazopanib-after-immunotherapy-for-advanced-kidney-cancer/

Real world use of pazopanib after immunotherapy for ... The estimated overall survival rate of pazopanib after immunotherapy at 6 and 12 months was 93% and 89%, respectively. 42% of patients reported an adverse event ...

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

Efficacy and Treatment Outcomes of First-line Pazopanib ... Conclusion: These data demonstrate that pazopanib is well-tolerated and effective as first-line treatment in patients with favorable-intermediate risk ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2012/022465s-010S-012lbl.pdf

VOTRIENT (pazopanib) tablets Label - accessdata.fda.gov WARNINGS AND PRECAUTIONS-----------------. • Increases in serum transaminase levels and bilirubin were observed. Severe and fatal hepatotoxicity has ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19509175/

Phase I Trial of Pazopanib in Patients With Advanced Cancer Pazopanib was generally well tolerated and showed antitumor activity across various tumor types. A monotherapy dose of 800 mg once daily was selected for phase ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02706366

Pazopanib Hydrochloride in Treating Patients With ... 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 ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35803859/

A Study of Pazopanib Safety and Efficacy in Patients With ... Conclusion: These data suggests that pazopanib is tolerated and effective in aRCC patients with PS2 and represents a treatment option for patients who cannot ...