Pazopanib + Abexinostat for Kidney Cancer

Recruiting at 1 trial location

Overseen By Rahul Aggarwal, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Xynomic Pharmaceuticals, Inc.

Disqualifiers: Untreated CNS metastases, Hypertension, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: Up to approximately 4 years

413 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with advanced kidney cancer that cannot be surgically removed or has metastasized. It compares the effects of pazopanib (a cancer medication) with either abexinostat (an experimental treatment) or a placebo (a substance with no active drug) to determine which is more effective. The trial seeks participants with kidney cancer that includes a clear cell component, who have not received certain prior treatments, and whose conditions are stable enough for participation. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking any prohibited medications at least 7 days or 5 half-lives before starting the study drug. However, the protocol does not specify which medications are prohibited, so it's best to discuss your current medications with the study team.

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

Research has shown that combining pazopanib with abexinostat is generally well-tolerated. Earlier studies found this combination manageable for most patients, allowing them to undergo treatment without serious side effects. Common side effects included tiredness, nausea, and diarrhea, but these were not severe for most individuals.

Pazopanib alone has FDA approval for certain types of cancer, indicating its safety is well understood. Previous studies on adding abexinostat did not significantly increase serious side effects.

Current evidence suggests that using pazopanib and abexinostat together is safe. However, side effects can vary from person to person. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney cancer?

Researchers are excited about pazopanib combined with abexinostat for kidney cancer because this combination targets cancer cells in a unique way. Pazopanib is already known for blocking proteins that help tumors grow new blood vessels, starving the cancer. Abexinostat, on the other hand, works by inhibiting enzymes that affect gene expression in cancer cells, potentially enhancing the effectiveness of pazopanib. This dual approach could offer a more powerful treatment compared to standard therapies that typically involve single-agent tyrosine kinase inhibitors like sunitinib or pembrolizumab. By pairing these mechanisms, there's hope for improved outcomes for patients with kidney cancer.

What evidence suggests that this trial's treatments could be effective for kidney cancer?

Research shows that combining pazopanib with abexinostat might help treat renal cell carcinoma (RCC), a type of kidney cancer. In this trial, participants will receive either the combination of pazopanib and abexinostat or pazopanib with a placebo. Studies have found that adding abexinostat to pazopanib improves treatment tolerance and can lead to longer-lasting responses and survival. Patients who received this combination also showed good disease control. While pazopanib alone treats RCC, adding abexinostat could enhance its effectiveness. These findings suggest that this combination could offer new hope for patients with advanced kidney cancer. ^{1 4 5 6 7}

Who Is on the Research Team?

Pamela Munster, M.D.

Principal Investigator

University of California, San Francisco

Rahul Aggarwal, M.D.

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Adults with advanced kidney cancer that hasn't spread to the brain can join this study. They should have clear cell renal carcinoma, measurable disease, and no prior treatments with certain cancer drugs. Good blood counts and organ function are needed, and they must be at least two weeks out from previous treatments.

Inclusion Criteria

It has been at least 2 weeks since my last cancer treatment.

Your disease can be measured by the doctor using specific guidelines.

I haven't been treated with VEGF inhibitors but may have had one round of immunotherapy.

Exclusion Criteria

I have lasting side effects from cancer treatment, but not hair loss.

I have had another cancer within the last 3 years, but it was either skin cancer, a localized cancer that hasn't spread, or a non-invasive bladder cancer.

I haven't taken any forbidden medications recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive pazopanib plus abexinostat or pazopanib plus placebo in 28-day cycles until disease progression or unacceptable toxicity

Up to approximately 4 years

Visits on Day 1 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 4 years

Every 3 months follow-up until death or study closure

Crossover

Participants in the placebo arm may cross over to receive pazopanib plus abexinostat upon disease progression

Until disease progression or unacceptable toxicity

What Are the Treatments Tested in This Trial?

Interventions

• Abexinostat
• Pazopanib

Trial Overview The RENAVIV trial is testing whether adding Abexinostat to Pazopanib improves outcomes in kidney cancer compared to using Pazopanib alone. Participants will be randomly assigned to receive either the combination or just Pazopanib with a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Pazopanib plus abexinostat Experimental Treatment 2 Interventions

Randomized patients will receive a combination of pazopanib plus abexinostat. The patients will receive pazopanib by mouth (p.o.) daily on Days 1 to 28 of each treatment cycle and will receive abexinostat p.o twice daily (BID) on Days 1 to 4, 8 to 11, and 15 to 18 of every 28-day cycle, 2 doses 4 hours apart. Patients will be instructed to take their once- daily oral dose of pazopanib and BID oral dose of abexinostat at the same time each day.

Group II: Pazopanib plus placebo Placebo Group 2 Interventions

Randomized patients will receive a combination of pazopanib plus abexinostat matching placebo. The patients will receive pazopanib by mouth (p.o.) daily on Days 1 to 28 of each treatment cycle and will receive abexinostat matching placebo p.o BID on Days 1 to 4, 8 to 11, and 15 to 18 of every 28-day cycle, 2 doses 4 hours apart. Patients will be instructed to take their once- daily oral dose of pazopanib and BID oral dose of placebo at the same time each day.

Pazopanib is already approved in United States, European Union, China for the following indications:

Approved in United States as Votrient for:

• Advanced renal cell carcinoma (kidney cancer)
• Soft tissue sarcoma

Approved in European Union as Votrient for:

• Advanced renal cell carcinoma (kidney cancer)
• Soft tissue sarcoma

Approved in China as pazopanib for:

• Metastatic renal cell carcinoma (mRCC)

Who Is Running the Clinical Trial?

Xynomic Pharmaceuticals, Inc.

Lead Sponsor

Trials

11

Recruited

1,200+

Published Research Related to This Trial

Pazopanib significantly improves progression-free survival in patients with chemotherapy-failing nonadipocytic soft tissue sarcomas, increasing it from 1.6 months to 4.6 months based on Phase II and Phase III clinical trials.

The safety profile of pazopanib is manageable, allowing for high dose intensity over time, making it a viable option as part of the standard care for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib, a new therapy for metastatic soft tissue sarcoma. Verweij, J., Sleijfer, S.[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]

Pazopanib is a potent pan-VEGF inhibitor that has shown clinical efficacy in treating metastatic renal cell carcinoma, leading to its recent FDA approval.

In a Phase III clinical trial, pazopanib demonstrated similar effectiveness to other approved treatments but exhibited different toxicity profiles, which may help differentiate it from other VEGFR inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib: therapeutic developments. Limvorasak, S., Posadas, EM.[2021]

Pazopanib, a multikinase inhibitor, was approved by the US FDA in October 2009 for treating advanced renal cell carcinoma, highlighting its significance in cancer therapy.

The drug targets vascular endothelial growth factor receptors, which play a crucial role in tumor growth and blood vessel formation, making it an effective option for managing this type of kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib. Bukowski, RM., Yasothan, U., Kirkpatrick, P.[2021]

Pazopanib, an oral tyrosine kinase inhibitor approved for renal cell carcinoma and soft tissue sarcoma, was primarily excreted unchanged in feces, indicating that it is mainly eliminated through the digestive system rather than the kidneys, with 82.2% of the dose found in feces.

The study found that the absolute oral bioavailability of pazopanib tablets ranged from 14% to 39%, suggesting that while pazopanib is effective, its absorption can vary significantly among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer. Deng, Y., Sychterz, C., Suttle, AB., et al.[2021]

Pazopanib is an FDA-approved multi-kinase inhibitor effective in treating advanced renal cell carcinoma (RCC), showing significant clinical activity in metastatic cases.

The drug not only targets VEGF receptors but also affects other receptors, which contributes to its side-effect profile, indicating a broader mechanism of action beyond just inhibiting VEGF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib and anti-VEGF therapy. Drabkin, HA.[2021]

Pazopanib is an effective treatment for advanced renal cell carcinoma, showing significantly better progression-free survival and objective response rates compared to placebo, and is noninferior to sunitinib in terms of efficacy.

Patients preferred pazopanib over sunitinib primarily due to its better tolerability and quality of life outcomes, despite pazopanib causing more abnormal liver function tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib: a review of its use in the management of advanced renal cell carcinoma. McCormack, PL.[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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03592472

NCT03592472 | A Study of Pazopanib With or Without ... This is a randomized, Phase 3, double-blind, placebo-controlled study of pazopanib plus abexinostat versus pazopanib plus placebo in patients with locally ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39509670/

Updated Survival Follow-Up for Phase Ib Trial of the ... Conclusion: Abexinostat added to pazopanib shows extended tolerability and long-term responses and survival. PBMC HDAC2 levels, the abexinostat ...

3. trial.medpath.com trial.medpath.com/clinical-trial/045d55db6d2b30a4/nct03592472-pazopanib-abexinostat-renal-cell-carcinoma

A Study of Pazopanib With or Without Abexinostat in Patients ... This is a randomized, Phase 3, double-blind, placebo-controlled study of pazopanib plus abexinostat versus pazopanib plus placebo in patients with locally ...

4. kidneycancer.org kidneycancer.org/trial/a-study-of-pazopanib-with-or-without-abexinostat-in-patients-with-locally-advanced-or-metastatic-renal-cell-carcinoma-renaviv/

A Study of Pazopanib With or Without Abexinostat in ... This is a randomized, Phase 3, double-blind, placebo-controlled study of pazopanib plus abexinostat versus pazopanib plus placebo in patients with locally ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT378161

Updated survival follow-up for phase I study of abexinostat ... We report the updated survival follow-up for patients treated with abexinostat and pazopanib in a phase Ib trial. Methods: Patients with solid tumor ...

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

Pazopanib as a possible option for the treatment of metastatic ... Treatment reality and outcome data of patients with advanced papillary renal cell carcinoma – data from the German prospective RCC-Registry Ann Oncol 2017 ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03592472/

Clinical Trial: NCT03592472 This is a randomized, Phase 3, double-blind, placebo-controlled study of pazopanib plus abexinostat versus pazopanib plus placebo in patients ...