Axitinib for Pheochromocytoma/Paraganglioma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests axitinib, a medication, to determine its effectiveness for people with pheochromocytoma or paraganglioma, rare tumors that can develop in various body parts. Researchers aim to discover if axitinib can slow or halt the spread of these tumors and assess how long patients remain free from disease progression. This study suits adults diagnosed with these tumors who show signs of spreading. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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 there any evidence suggesting that axitinib is likely to be safe for humans?

Research has shown that axitinib has been studied for its safety in individuals with conditions like pheochromocytoma and paraganglioma. In one study involving 37 patients, all experienced some side effects. High blood pressure was the most common, affecting about 67% of participants.

This treatment has not been tested in individuals under 18 due to insufficient information on its effects in children. While axitinib can cause side effects, it has shown promise in shrinking tumors for this patient group.

Prospective trial participants should discuss these findings with their doctor to understand their implications. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Axitinib is unique because it targets the vascular endothelial growth factor (VEGF) receptors, which play a vital role in tumor blood vessel growth. Unlike standard treatments for pheochromocytoma and paraganglioma, which primarily focus on managing hormone secretion and tumor growth through surgery or medications like alpha-blockers, axitinib specifically inhibits pathways that fuel tumor blood supply. This targeted approach could offer a new way to control tumors that are recurrent or cannot be surgically removed, potentially slowing or stopping their growth more effectively. Researchers are excited about axitinib because it offers a novel mechanism of action that could improve outcomes for patients with these challenging conditions.

What evidence suggests that axitinib might be an effective treatment for pheochromocytoma/paraganglioma?

Research has shown that axitinib, the treatment under study in this trial, might help shrink tumors in people with malignant pheochromocytoma and paraganglioma. Studies have found that axitinib blocks the blood vessels tumors need to grow, potentially slowing or reversing tumor growth. Early results indicate that some patients have experienced tumor shrinkage while taking axitinib. This treatment targets a specific process in the body called VEGF, crucial for the tumor's blood supply. Overall, axitinib appears to be a promising treatment option for these conditions. ^{1 2 3 4 6}

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

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]

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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT01967576?term=Inlyta&rank=9

Phase II Study of Axitinib (AG-013736) With Evaluation ... Pre-clinical data suggests that the anti-tumor activity of axitinib may result from its anti-angiogenic activity and that this is reversible when treatment is ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.4602

Single agent axitinib in the management of patients with ... Axitinib, two VEGF tyrosine kinase inhibitors with similar characteristics, in the management of malignant pheochromocytoma and paragangliomas.

3. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=14-C-0001&&query=Malignant%20Germ

NIH Clinical Center: Search the Studies Pre-clinical data suggests that the anti-tumor activity of axitinib may result from its anti-angiogenic activity and that this is reversible when treatment is ...

4. ascopubs.org ascopubs.org/doi/10.1200/jco.2015.33.7_suppl.457

Phase II clinical trial of axitinib in metastatic ... Preliminary data shows axitinib can result in tumor shrinkage in patients with a diagnosis of malignant P/PG.

5. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT01967576/

Clinical Trial: NCT01967576 Phase II study of Axitinib (AG-013736) with evaluation of the VEGF-pathway in metastatic, recurrent or primary unresectable pheochromocytoma/paraganglioma.

6. academic.oup.com academic.oup.com/jes/article/8/7/bvae092/7665818

A Targetable Receptor Tyrosine Kinase in Metastatic ... Progression-free survival was 12.3 months. Importantly, adverse reactions were reported from all 37 patients, the most common of which were hypertension (67%), ...