Axitinib in Treating Patients with Metastatic, Recurrent, or Primary Unresectable Pheochromocytoma or Paraganglioma

Status: Active


This phase II trial studies how well axitinib works in treating patients with pheochromocytoma or paraganglioma that has spread to other parts of the body (metastatic), has come back (recurrent), or cannot be removed by surgery (refractory). Axitinib may stop the growth or shrink tumor cells by blocking some of the enzymes needed for cell growth.

Eligibility Criteria

Inclusion Criteria

  • Adults with a confirmed pathologic diagnosis of pheochromocytoma/paraganglioma by a Columbia University Medical Center (CUMC)/New York-Presbyterian Hospital (NYPH) laboratory when such tissue is available to confirm or in the event that outside tissue is not available: * An outside pathology report confirms the diagnosis of pheochromocytoma/paraganglioma (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 (fluorodopa [F-DOPA], dotatate, F-dopamine or metaiodobenzylguanidine [MIBG]).
  • Imaging confirmation of metastatic disease.
  • Measurable disease at the time of enrollment as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • A life expectancy of at least 3 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2.
  • 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 investigational new drug (IND)” trial. Last surgery more than 4 weeks prior to enrollment, to allow for wound healing. Core biopsies or fine-needle aspiration (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.
  • 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. * 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 blood cell count (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.
  • Aspartate aminotransferase (AST) =< 2.5 x ULN, alanine aminotransferase (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.
  • 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/mm^3.
  • Platelet count >= 50,000/mm^3.
  • 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.

Exclusion Criteria

  • 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 mmHg 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 tyrosine kinase inhibitor (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.

Locations & Contacts

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Contact: Antonio Tito Fojo
Phone: 212-305-9422

Trial Objectives and Outline


I. To determine the response rate (RR) of metastatic or locally advanced pheochromocytoma/paraganglioma to axitinib administered daily.


I. Determine the progression-free survival.

II. 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.

III. Perform pharmacogenomics analyses of drug metabolism and transport proteins through germline deoxyribonucleic acid (DNA) examination.

OUTLINE: This is a dose-escalation study.

Patients receive axitinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for at least 1 month.

Trial Phase & Type

Trial Phase

Phase II

Trial Type


Lead Organization

Lead Organization
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center

Principal Investigator
Antonio Tito Fojo

Trial IDs

Primary ID AAAR5314
Secondary IDs NCI-2019-01821 ID NCT03839498