Pazopanib + PCI-24781 for Metastatic Cancer

Overseen By Early Phase Cancer Clinical Trials Recruitment

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pamela Munster

Must not be taking: QT prolonging drugs

Disqualifiers: Active infections, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and optimal dose of a combination of two treatments: pazopanib (a cancer medication) and PCI-24781 (an experimental treatment) for individuals with advanced solid tumors that have metastasized. The trial aims to evaluate the effectiveness of these treatments in combating various cancers, including kidney, thyroid, soft tissue sarcoma, and ovarian cancer. It may suit patients whose cancer has progressed despite previous treatments and who lack other effective options. 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 combination therapy.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications at least 14 days or five half-lives (whichever is shorter) before starting the study drug and for the duration of the study. If you are on medications that are prohibited by the trial, you will need to discontinue them.

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

Earlier studies found that pazopanib was generally well-tolerated by patients with advanced kidney cancer. Common side effects included diarrhea, high blood pressure, and changes in hair color, but most people managed these with standard treatments.

Less information is available for the combination of pazopanib and PCI-24781. As this trial is in its early stages, researchers are still learning about the safety of this combination for patients. The main goal is to determine the best dose that patients can handle without too many side effects.

Since this combination is still being tested, discussing any concerns with a doctor before deciding to join the trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about pazopanib and PCI-24781 for treating metastatic cancer because of their unique mechanisms of action. Unlike traditional chemotherapy, which targets rapidly dividing cells indiscriminately, pazopanib is a targeted therapy known as a tyrosine kinase inhibitor, specifically blocking proteins that help cancer cells grow. PCI-24781, on the other hand, is a histone deacetylase (HDAC) inhibitor, which can reactivate suppressed genes that fight cancer. This combination aims to attack cancer from multiple angles, potentially leading to more effective control of the disease with possibly fewer side effects compared to conventional treatments.

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

Research shows that pazopanib alone has promising results in treating advanced cancers like kidney cancer. Studies have found that 27% to 33% of patients respond to the treatment, and 81% to 89% have their disease controlled. Participants in these studies lived for a period without their cancer worsening.

This trial examines the combination of pazopanib with another drug, PCI-24781, as PCI-24781 might enhance the cancer-fighting effects of pazopanib. Although limited data exists on this combination, the interaction between these drugs suggests they might more effectively shrink tumors. Early studies focus on ensuring the combination's safety and determining the best dose, with the hope of achieving better results than with pazopanib alone. ^{1 3 6 7 8}

Who Is on the Research Team?

Pamela Munster, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Adults with advanced solid tumors who have adequate organ function and no recent transfusions. Women must be non-pregnant, not nursing, and using contraception if of childbearing potential. Excludes those with certain heart conditions, uncontrolled infections, or brain metastases.

Inclusion Criteria

My cancer is advanced, confirmed by lab tests, and matches the specific types needed for Phase Ib.

Measurable disease by RECIST 1.1

It's been over 4 weeks or five half-lives since my last cancer treatment.

Exclusion Criteria

I haven't had any cancer except for skin cancer in the last 5 years.

I have serious stomach or intestine problems that could cause bleeding.

I do not have active hepatitis C or B, HIV, or any uncontrolled infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation and Expansion

Participants receive pazopanib in combination with PCI-24781 to determine safety, tolerability, and maximum tolerated dose

4 weeks

Weekly visits for dose escalation monitoring

Treatment

Participants continue receiving the combination treatment to assess efficacy and pharmacokinetics

4 months

Bi-weekly visits for efficacy evaluation

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Quarterly visits for survival and progression monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Pazopanib
• PCI-24781

Trial Overview The trial is testing the combination of two drugs, Pazopanib and PCI-24781, to find the safest dose for treating advanced solid tumors. It's an early-phase study where everyone gets the treatment without being compared to a control group.

How Is the Trial Designed?

Group I: Panobinostat with PC124871 Experimental Treatment 1 Intervention

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?

Pamela Munster

Lead Sponsor

Trials

8

Recruited

180+

Pharmacyclics LLC.

Industry Sponsor

Trials

114

Recruited

13,800+

Dr. Maky Zanganeh

Pharmacyclics LLC.

Chief Executive Officer

Degree from Louis Pasteur University in Strasbourg, France; MBA from Schiller International University in France

Dr. Ellie Im

Pharmacyclics LLC.

Chief Medical Officer

MD from an unspecified institution

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease

Collaborator

Trials

1

Recruited

90+

Xynomic Pharmaceuticals, Inc.

Industry Sponsor

Trials

11

Recruited

1,200+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01543763

Pazopanib in Combination With PCI-24781 in Patients ... Pazopanib is a potent, multi-targeted tyrosine kinase inhibitor44 of VEGFR-1, -2, -3, PDGFR-α and -β and c-kit approved for metastatic renal cell carcinoma ...

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

Pazopanib as a possible option for the treatment of metastatic ... Pazopanib alone as first-line treatment gave overall response rates ranging from 27% to 33%, disease control rates of 81–89%, median progression free survival ...

3. researchgate.net researchgate.net/publication/339867191_Phase_I_study_of_pazopanib_PAZ_in_combination_with_PCI-24781_PCI_in_patients_pts_with_metastatic_solid_tumors_with_new_tumor_proliferation_imaging_correlates_in_renal_cell_carcinoma_RCC_and_sarcoma

Phase I study of pazopanib (PAZ) in combination with PCI ... Phase I study of pazopanib (PAZ) in combination with PCI-24781 (PCI) in patients (pts) with metastatic solid tumors with new tumor proliferation ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8870577/

Efficacy of Pazopanib in the Treatment of Metastatic ... In the present case, pazopanib treatment was effective, as previously reported, and its efficacy lasted for 11 months. However, detailed data regarding the ...

5. csfshayna.org csfshayna.org/site/literature-review-on-the-effectiveness-of-pazopanib-votrient/

Literature Review on the Effectiveness of Pazopanib (Votrient) This single-arm, multicenter, phase 2 study evaluated the safety and antitumor activity of pazopanib in patients with unresectable or metastatic conventional ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01543763?intr=S78454&aggFilters=studyType:int&viewType=Table&rank=1

Study Details | Pazopanib in Combination With PCI-24781 ... Individual Patients: Allows a single patient, with a serious disease or condition who cannot participate in a clinical trial, access to a drug or biological ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20008644/

Efficacy and safety of pazopanib in patients with metastatic ... Pazopanib demonstrated durable activity in patients with advanced RCC and was generally well tolerated in this population.

8. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT01543763/

Trial | NCT01543763 Phase I Study to Evaluate the Tolerability, Efficacy, and Safety of Pazopanib in Combination With PCI-24781 in Patients With Metastatic Solid Tumors.