Axitinib for Pheochromocytoma/Paraganglioma

Recruiting at 1 trial location

Overseen By Research Nurse Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Columbia University

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Unstable hypertension, Untreated brain metastases, Pregnancy, others

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

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: 16 weeks

6 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Primary Objective: To determine the response rate (RR) of metastatic or locally advanced pheochromocytoma/paraganglioma to axitinib administered daily. Secondary Objectives: * Determine the progression-free survival. * In an exploratory manner examine the extent of activation of the VEGFR pathway in pheochromocytoma/paraganglioma using a semi-quantitative immunohistochemistry assay and examine the relationship with response to therapy. * Perform pharmacogenomics analyses of drug metabolism and transport proteins through germline DNA examination.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use certain drugs that affect liver enzymes (CYP3A4 and CYP1A2) or require certain blood thinners. It's best to discuss your current medications with the trial team to see if any need to be adjusted.

Is axitinib safe for use in humans?

Axitinib, also known as Inlyta, has been generally well tolerated in clinical trials for various conditions, including renal cell carcinoma and neuroendocrine tumors. Common side effects include diarrhea, high blood pressure, fatigue, nausea, and vomiting. However, it can cause serious high blood pressure in some patients, which may require stopping the treatment. ^{1 2 3 4 5}

How does the drug Axitinib differ from other treatments for pheochromocytoma/paraganglioma?

Axitinib is a tyrosine kinase inhibitor, which targets specific proteins involved in tumor growth and blood vessel formation, making it a novel option for pheochromocytoma/paraganglioma where no standard treatments are approved. This mechanism of action is different from other therapies that may not specifically target these pathways. ^{6 7 8 9 10}

Who Is on the Research Team?

Antonio Fojo, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

Adults diagnosed with advanced pheochromocytoma/paraganglioma who haven't had surgery, chemotherapy, or radiotherapy in the last 4 weeks (6 for certain drugs). They must have measurable disease, be expected to live at least 3 months, and have an ECOG status ≤2. Pregnant women and those with unstable blood pressure or other severe conditions are excluded.

Inclusion Criteria

Adults with a confirmed diagnosis of pheochromocytoma/paraganglioma by a specific laboratory test.

Your doctor has confirmed that the cancer has spread to other parts of your body using imaging tests.

Last dose of chemotherapy or experimental therapy more than 4 weeks (6 weeks in the case of nitrosourea) prior to enrollment date; 2 weeks if the last therapy was received as part of a 'phase 0' or 'exploratory IND' trial

Exclusion Criteria

Pregnancy

You have tumors that can be completely removed with surgery.

Patients with large masses in their abdomen or lungs that could cause bleeding will be evaluated individually after consulting with different medical experts.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Axitinib therapy for 16 weeks, with clinic visits every 4 weeks to monitor therapy

16 weeks

4 visits (in-person)

Follow-up

Participants are monitored for progression-free survival and response rate after treatment

Up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Axitinib

Trial Overview The trial is testing Axitinib's effectiveness on metastatic or locally advanced pheochromocytoma/paraganglioma. It aims to see how well patients respond to daily treatment, measure how long they live without the disease getting worse, and explore genetic factors related to drug metabolism.

How Is the Trial Designed?

Group I: Axitinib (AG-013736) Experimental Treatment 1 Intervention

Subjects with Recurrent or Primary Unresectable Pheochromocytoma/Paraganglioma will receive 16 weeks of therapy (Axitinib), and be seen in clinic every 4 weeks to monitor therapy.

Axitinib is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Inlyta for:

• Renal cell carcinoma

Approved in United States as Inlyta for:

• Advanced renal cell carcinoma

Approved in United Kingdom as Inlyta for:

• Advanced renal cell carcinoma

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In a phase II study involving 32 patients with metastatic melanoma, axitinib demonstrated an objective response rate of 18.8%, indicating it can provide clinical activity as a treatment option.

Axitinib was generally well tolerated, with common side effects including fatigue and hypertension, but it also posed risks such as a serious bowel perforation in one patient, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter, phase II study of axitinib, a selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, in patients with metastatic melanoma. Fruehauf, J., Lutzky, J., McDermott, D., et al.[2020]

A review of seven targeted cancer therapies (sunitinib, pazopanib, bevacizumab, temsirolimus, axitinib, everolimus, and sorafenib) revealed that all these medications are associated with adverse events, highlighting the importance of monitoring patients closely.

Effective management strategies for these side effects can prevent them from becoming severe, which is crucial to maintaining the full efficacy of the treatments and avoiding unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A contemporary update on rates and management of toxicities of targeted therapies for metastatic renal cell carcinoma. Alasker, A., Meskawi, M., Sun, M., et al.[2022]

Axitinib is an effective second-line treatment for advanced renal cell carcinoma (RCC), showing significantly prolonged median progression-free survival compared to sorafenib in the phase III AXIS trial.

The tolerability profile of axitinib is manageable, with common side effects including diarrhea, hypertension, and fatigue, making it a viable option for patients who have already received other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib: a review in advanced renal cell carcinoma. Keating, GM.[2018]

Citations

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

Axitinib for the treatment of metastatic renal cell carcinoma: recommendations for therapy management to optimize outcomes. [2018]

2. England pubmed.ncbi.nlm.nih.gov

A phase II study of axitinib in advanced neuroendocrine tumors. [2023]

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

Multicenter, phase II study of axitinib, a selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, in patients with metastatic melanoma. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

A contemporary update on rates and management of toxicities of targeted therapies for metastatic renal cell carcinoma. [2022]

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

Axitinib: a review in advanced renal cell carcinoma. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Personalized drug testing in human pheochromocytoma/paraganglioma primary cultures. [2022]

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

Synergistic Highly Potent Targeted Drug Combinations in Different Pheochromocytoma Models Including Human Tumor Cultures. [2021]

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

Targeted Therapies in Pheochromocytoma and Paraganglioma. [2023]

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

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Genotype-phenotype correlations in pheochromocytoma and paraganglioma: a systematic review and individual patient meta-analysis. [2021]