PheochromocytomaPhase 2NCT03839498
Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Pheochromocytoma/Paraganglioma
A Phase 2 study testing Axitinib in people with Pheochromocytoma and Paraganglioma, run by Columbia University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pheochromocytoma, Paraganglioma
- What is being tested?
- Axitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jan 2019to Feb 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults with a confirmed pathologic diagnosis of pheochromocytoma/paraganglioma by a CUMC/NYPH laboratory when such tissue is available to confirm.
- In the event that outside tissue is not available:
- An outside pathology report confirms the diagnosis of Pheo/PGL, AND the patient has nuclear medicine imaging studies that would only be positive in an adult patient with a diagnosis of Pheo/PGL (F-DOPA, Dotatate, F-Dopamine or MIBG)
- Imaging confirmation of metastatic disease
- Measurable disease at the time of enrollment as per RECIST 1.1.
- A life expectancy of at least 3 months and ECOG performance status ≤ 2
Show all 23Show fewer
- Age ≥ 18 years
- Information available or pending regarding possible genetic alterations that can explain the patient's pheochromocytoma/paraganglioma (mutations in SDHB, SDHV or VHL genes)
- 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. Last surgery more than 4 weeks prior to enrollment, to allow for wound healing. Core biopsies or FNA will not require any waiting period
- Last radiotherapy treatment ≥ 4 weeks prior to starting treatment with this protocol and there must be sites of measurable disease that did not receive radiation
- Prior therapeutic MIBG is allowed
- Organ and marrow function as defined below:
- Total bilirubin ≤ 1.5 x ULN (upper limit of normal), unless the patient meets the criteria for Gilbert's Syndrome. The upper limit value for bilirubin for subjects with Gilbert's Syndrome is less than 3 mg/dl.
- o Note: A diagnosis of Gilbert's disease will be made in the presence of (1) unconjugated hyperbilirubinemia noted on several occasions; (2) normal results from CBC count, reticulocyte count, and blood smear; (3) normal liver function test results; and (4) an absence of other disease processes that can explain the unconjugated hyperbilirubinemia.
- AST ≤ 2.5 x ULN, ALT ≤ 2.5 x ULN
- Amylase and lipase equal to, or less than, the institutional ULN.
- Creatinine clearance ≥ 40 ml/min (estimated or measured creatinine clearance) or serum creatinine ≤ 1.6 mg/dl
- o Random urine protein < 20 mg/dL. If ≥ 20 mg/dL then a 24-hour urine protein collection will be performed to accurately demonstrate that the 24-hour total is <1000 mg, the level acceptable for enrollment on study
- Absolute neutrophil count ≥ 500/mm3
- Platelet count ≥ 50,000/ mm3
- Ability to understand and sign an informed consent document.
- Ability and willingness to follow the guidelines of the clinical protocol.
- Because the effects of chemotherapy on the developing human fetus are potentially harmful, women of childbearing potential and men who participate in the study must agree to use adequate contraception (hormonal or barrier methods) before, during the study and for a period of 3 months after the last dose of chemotherapy.
Who cannot join
- Patients with pheochromocytoma/paraganglioma tumors potentially curable by surgical excision alone as determined by the Principal Investigator in discussions with the surgical consultants
- Patients who have large abdominal masses impinging on bowel or pulmonary masses with encroached vessels and a potential to bleed will be considered on case by case basis after careful consultation with multiple disciplines such as radiologists and surgeons with main intent being patient safety.
- Unstable hypertension defined as a systolic blood pressure >150 mm Hg or diastolic pressure > 90 mmHg despite optimal medical management.
- Untreated brain metastases (or local treatment of brain metastases within the last 3 months) due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic adverse events.
- Pregnancy, due to the possible adverse effects on the developing fetus.
- Lactating women who are breast-feeding due to the possibility of transmitting axitinib to the child.
Show all 22Show fewer
- The presence of a second malignancy, other than squamous cell carcinoma of the skin or in situ cervical cancer because it will complicate the primary objective of the study. Cancer survivors who have been free of disease for at least one year can be enrolled in this study.
- Patients with evidence of a bleeding diathesis
- Patients must not have received prior therapy with a TKI. Prior TKI usage in pheochromocytoma affects the same pathway as axitinib.
- Gastrointestinal abnormalities including:
- Inability to take oral medications
- Requirement for intravenous alimentation
- Prior surgical procedure affecting absorption including total gastric resection
- Treatment for active peptic ulcer disease in the past 6 months
- Active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy.
- Malabsorption syndrome
- Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, and delavirdine).
- Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (i.e., carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John's wort).
- Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose anticoagulants for maintenance of patency of central venous access devices or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed.
- Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
- Any of the following within 12 months prior to study drug administration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and within 6 months before study drug administration for deep vein thrombosis or pulmonary embolism.
- Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Irving Medical Center
New York, New York, 10031
About this study
Official title: Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Metastatic, Recurrent or Primary Unresectable Pheochromocytoma/Paraganglioma
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.
Read the detailed description
The long-term survival for malignant pheochromocytoma/paraganglioma (PHEO/PGL) may be limited because of its hormonal effects as well as its aggressive behavior and dissemination, particularly in some hereditary PHEO/PGL. Although several therapeutic modalities have been used to palliate malignant PHEO/PGL, a continued search for new agents to address the malignancy is needed to improve outcomes. One approach is to utilize drugs that target signaling pathways leading to decreased proliferation and survival of cancer cells. Some data in the literature suggests that in malignant PHEO/PGL, VEGF seems to play a role in the biology of the cancer and thus, its inhibition could reduce tumor growth. Sunitinib and imatinib has been used in a limited number of malignant pheochromocytomas with varying responses. Axitinib was designed to inhibit VEGFR that participates in tumor angiogenesis. In order to determine the activity of axitinib in tumor and hormonal responses in malignant PHEO/PGL, it will be used as a single agent in this study. The combination of cyclophosphamide; vincristine and dacarbazine have been shown to produce partial responses in malignant PHEO/PGL. The majority of the patients may have already received this combination or will receive this combination chemotherapy in the future. The goal is to develop multiple lines of effective treatments for this disease.
- Conditions
- Pheochromocytoma, Paraganglioma
- Being tested
- Axitinib
- Keywords
- Axitinib
- Medical subject headings
- Pheochromocytoma, Paraganglioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AxitinibDrug
Also called AG-013736
Axitinib (AG-013736) is an oral, potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3.
Starting dose level 1: 5 mg every morning; 5 mg every evening. Dose level 2: 7 mg every morning; 7 mg every evening. Dose level 3: 10 mg every morning; 10 mg every evening. Dose level -1: 3 mg every morning; 3 every evening. Dose level -2: 2 mg every morning; 2 mg every evening.
Axitinib is supplied as 1 and 5-mg tablets and is administered orally twice a day with or without food, each morning and evening (i.e., every 12 hours). Axitinib will be given as self-administered.
| Study group | Role | What they receive |
|---|---|---|
| Axitinib (AG-013736) | Experimental | 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. Receives: Drug: Axitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate (RR)
This study is designed to determine the percentage of patients whose cancer shrinks or disappears after treatment.
Measured: Up to 16 weeks
Secondary outcomes (1)
Progression-free survival
The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse.
Measured: Duration of time from start of treatment to time of progression or death, whichever occurs first; an average of up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2019
- Study start22 Jan 2019
- Primary completionJan 2027 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PheochromocytomaStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, Antonio Fojo, Columbia University
- Investigators
- Antonio Fojo, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03839498
- Sponsor's protocol ID
- AAAR5314
- Status last verified
- Feb 2026
- First submitted
- 31 Jan 2019
- Last updated
- 2 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Metastatic, Recurrent or Primary Unresectable Pheochromocytoma/Paraganglioma
- ClinicalTrials.gov ID
- NCT03839498
- Acronym / sponsor ID
- AAAR5314
- Conditions
- Pheochromocytoma, Paraganglioma
- Keywords
- Axitinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 22 Jan 2019 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 15 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The long-term survival for malignant pheochromocytoma/paraganglioma (PHEO/PGL) may be limited because of its hormonal effects as well as its aggressive behavior and dissemination, particularly in some hereditary PHEO/PGL. Although several therapeutic modalities have been used to palliate malignant PHEO/PGL, a continued search for new agents to address the malignancy is needed to improve outcomes. One approach is to utilize drugs that target signaling pathways leading to decreased proliferation and survival of cancer cells. Some data in the literature suggests that in malignant PHEO/PGL, VEGF seems to play a role in the biology of the cancer and thus, its inhibition could reduce tumor growth. Sunitinib and imatinib has been used in a limited number of malignant pheochromocytomas with varying responses. Axitinib was designed to inhibit VEGFR that participates in tumor angiogenesis. In order to determine the activity of axitinib in tumor and hormonal responses in malignant PHEO/PGL, it will be used as a single agent in this study. The combination of cyclophosphamide; vincristine and dacarbazine have been shown to produce partial responses in malignant PHEO/PGL. The majority of the patients may have already received this combination or will receive this combination chemotherapy in the future. The goal is to develop multiple lines of effective treatments for this disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Axitinib (AG-013736) | Experimental | Drug: AxitinibSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Adults with a confirmed pathologic diagnosis of pheochromocytoma/paraganglioma by a CUMC/NYPH laboratory when such tissue is available to confirm.
- An outside pathology report confirms the diagnosis of Pheo/PGL, AND the patient has nuclear medicine imaging studies that would only be positive in an adult patient with a diagnosis of Pheo/PGL (F-DOPA, Dotatate, F-Dopamine or MIBG)
- Imaging confirmation of metastatic disease
- Measurable disease at the time of enrollment as per RECIST 1.1.
- A life expectancy of at least 3 months and ECOG performance status ≤ 2
Key exclusion criteria (22 listed)
- Patients with pheochromocytoma/paraganglioma tumors potentially curable by surgical excision alone as determined by the Principal Investigator in discussions with the surgical consultants
- Patients who have large abdominal masses impinging on bowel or pulmonary masses with encroached vessels and a potential to bleed will be considered on case by case basis after careful consultation with multiple disciplines such as radiologists and surgeons with main intent being patient safety.
- Unstable hypertension defined as a systolic blood pressure >150 mm Hg or diastolic pressure > 90 mmHg despite optimal medical management.
- Untreated brain metastases (or local treatment of brain metastases within the last 3 months) due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic adverse events.
- Pregnancy, due to the possible adverse effects on the developing fetus.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AxitinibAlso: AG-013736Axitinib (AG-013736) is an oral, potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. Starting dose level 1: 5 mg every morning; 5 mg every evening. Dose level 2: 7 mg every morning; 7 mg every evening. Dose level 3: 10 mg every morning; 10 mg every evening. Dose level -1: 3 mg every morning; 3 every evening. Dose level -2: 2 mg every morning; 2 mg every evening. Axitinib is supplied as 1 and 5-mg tablets and is administered orally twice a day with or without food, each morning and evening (i.e., every 12 hours). Axitinib will be given as self-administered. | Drug | Axitinib (AG-013736) |
Primary outcome
Response Rate (RR)
Time frame: Up to 16 weeks
This study is designed to determine the percentage of patients whose cancer shrinks or disappears after treatment.
1 secondary outcome
Progression-free survival
Time frame: Duration of time from start of treatment to time of progression or death, whichever occurs first; an average of up to 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2026.
- Individual participant dataSharing planned: No
Related trials for Pheochromocytoma
RecruitingObservational study
Adrenal Diseases in the Population of Modena: A Clinical-Epidemiological Database of Patients Referred to the Adrenal Disorders Outpatient Clinic of the Clinical Unit of Endocrinology at the Modena University Hospital (AOU Modena)
Cushing s Syndrome, Cushing Disease
Active, not recruitingObservational study
Natural History Study of Children and Adults With Medullary Thyroid Cancer
Medullary Thyroid Cancer
RecruitingObservational study
Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
Pheochromocytoma, Paraganglioma
RecruitingObservational study
Von Hippel-Lindau (VHL): Clinical Manifestations, Diagnosis, Management and Molecular Bases of Inherited Renal and Other Urologic Malignant Disorders
Kidney Cancer, Urologic Malignant Disorders
RecruitingPhase 2
Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015)
Pheochromocytoma/Paraganglioma, Pancreatic Neuroendocrine Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Fojo, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Axitinib in people with Pheochromocytoma and Paraganglioma, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response Rate (RR) (time frame: Up to 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2026.