Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Pheochromocytoma/Paraganglioma

NCT03839498 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AAAR5314
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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.
• 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.

Conditions

Pheochromocytoma; Paraganglioma

Keywords

Axitinib

Outcome Measures

Primary Outcomes (1)

• Response Rate (RR)

  This study is designed to determine the percentage of patients whose cancer shrinks or disappears after treatment.

  Up to 16 weeks

Secondary Outcomes (1)

• Progression-free survival

  Duration of time from start of treatment to time of progression or death, whichever occurs first; an average of up to 12 months

Study Arms (1)

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.

Drug: Axitinib

Interventions

Axitinib DRUG

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.

Also known as: AG-013736

Axitinib (AG-013736)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Columbia University: lead
• Pfizer: collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10031, United States

Location

MeSH Terms

Conditions

Pheochromocytoma; Paraganglioma

Interventions

Axitinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Antonio Fojo, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine at the Columbia University Medical Center, Dept of Med Hematology & Onc

Study Record Dates

• First Submitted: January 31, 2019
• First Posted: February 15, 2019
• Study Start: January 22, 2019
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)