Lenvatinib in Treating Patients With Metastatic or Advanced Pheochromocytoma or Paraganglioma That Cannot Be Removed by Surgery
Condition: Malignant Adrenal Gland Pheochromocytoma; Malignant Paraganglioma; Metastatic Adrenal Gland Pheochromocytoma
MeSH terms: Pheochromocytoma; Paraganglioma
Intervention: Laboratory Biomarker Analysis; Lenvatinib; Quality-of-Life Assessment
Intervention description: Correlative studies; Given PO; Ancillary studies
Intervention MeSH terms: Lenvatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well lenvatinib works in treating patients with
      pheochromocytoma or paraganglioma that has spread to other places in the body or cannot be
      removed by surgery. Lenvatinib may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed malignant secretory or non-secretory
             pheochromocytoma or paraganglioma that is unresectable and deemed inappropriate for
             alternative local regional therapeutic approaches

          -  Measurable disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

          -  Life expectancy > 24 weeks

          -  Absolute neutrophil count (ANC) >= 1500/mm^3

          -  White blood cell (WBC) count >= 3,000/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Hemoglobin >= 9.0 g/dL (5.6 mmol/L); NOTE: transfusions are not allowed =< 7 days
             prior to registration

          -  Total bilirubin =< 1.5 X upper limit of normal (ULN) (or total bilirubin =< 3.0 X ULN
             with direct bilirubin =< 1.5 X ULN in patients with well-documented Gilbert's
             Syndrome)

          -  Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X
             ULN

          -  Creatinine =< 1.5 x ULN

          -  Urine protein/creatinine ratio =< 1 OR 24-hour urine protein < 1.5 gram

          -  Negative pregnancy test done =< 7 days prior to registration, for women of
             childbearing potential only

          -  Blood pressure (BP) < 150 mmHg (systolic) and < 90 mmHg (diastolic); initiation or
             adjustment of BP medication is permitted prior to registration provided that the
             average of three BP readings at a visit prior to registration is < 150/90 mmHg; NOTE:
             all patients with secretory pheochromocytoma or paraganglioma are REQUIRED to: 1) be
             evaluated in consultation by a hypertension specialist with specific experience in the
             management of hypertension in the setting of catecholamine-secreting tumors (usually
             an endocrinologist, nephrologist, or a cardiologist), and in the setting of
             hormone-associated hypertension) receive alpha- and beta-adrenergic blockade for at
             least 7-14 days prior to initiation of lenvatinib; the hypertension specialist of
             record for each patient should be committed to closely following the patient during
             the clinical study with evaluation by said specialist required at cycle 1 and 2 and
             thereafter on an as needed basis

          -  Provide written informed consent

          -  Willing to return to enrolling institution for follow-up (during the active monitoring
             phase of the study)

          -  Ability to complete questionnaire(s) by themselves or with assistance

        Exclusion Criteria:

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Chemotherapy/systemic therapy, radiotherapy, immunotherapy or surgery =< 21 days prior
             to registration or kinase inhibitor therapy =< 14 days prior to registration or
             failure to recover from toxicities (to grade 1 or below) from treatment; NOTE:
             concurrent therapy with octreotide is allowed providing that tumor progression on this
             therapy has been demonstrated; concurrent therapy with bisphosphonates (e.g.
             zoledronic acid) or denosumab is also allowed; NOTE: an unlimited number of prior
             chemotherapeutic or biologic therapies for malignant pheochromocytoma or paraganglioma
             is permitted; this includes prior anti-angiogenesis therapies such as tyrosine kinase
             inhibitors

          -  Active or uncontrolled intercurrent illness including, but not limited to, ongoing or
             active infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia, or psychiatric illness/social situations that would limit
             compliance with study requirements

          -  Receiving any other investigational agent

          -  Current use of warfarin for any reason; NOTE: if patient can be safely transitioned to
             another anticoagulant, they may be eligible provided other criteria are satisfied

          -  Any of the following:

               -  Correct QT (QTc) prolongation (defined as a QTc interval >= 500 msecs)

               -  Left ventricular ejection fraction (LVEF) < institutional lower limits of normal
                  (LLN)

               -  Frequent ventricular ectopy

               -  Evidence of ongoing myocardial ischemia

          -  Receiving any medications or substances with risk of torsades de pointes; NOTE:
             medications or substances with known risk of torsades de pointes are prohibited;
             consult pharmacist for review if needed

          -  Known active and/or untreated brain metastases

          -  Known severe allergic or other prohibitive reactions to other tyrosine kinase
             inhibitors (TKI)

          -  Prior treatment with lenvatinib

          -  Any of the following conditions:

               -  Active peptic ulcer disease

               -  Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other
                  gastrointestinal conditions which increase the risk of perforation

               -  History of new abdominal fistula, gastrointestinal perforation or intra-abdominal
                  abscess =< 84 days prior to registration; NOTE: enrollment of patients with
                  chronic/canalized fistulous tracts (present for > 84 days) is allowed

               -  Serious or non-healing wound, ulcer, or bone fracture

               -  History of familial QTc prolongation syndrome

          -  Any of the following conditions =< 6 months prior to registration:

               -  Cerebrovascular accident (CVA) or transient ischemic attack (TIA)

               -  Serious or unstable cardiac arrhythmia

               -  Admission for unstable angina or myocardial infarction

               -  Cardiac angioplasty or stenting

               -  Coronary artery bypass graft surgery

               -  Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which has been
                  treated with therapeutic anticoagulation =< 30 days

               -  Arterial thrombosis

               -  Symptomatic peripheral vascular disease

          -  Other active malignancy =< 2 years prior to registration; EXCEPTIONS: non-melanotic
             skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior
             malignancy, they must not be receiving other specific treatment for their cancer;
             NOTE: adjuvant anti-estrogen/hormonal therapy for breast cancer is allowed