Pazopanib Hydrochloride in Treating Patients With Advanced or Progressive Malignant Pheochromocytoma or Paraganglioma

Stopped early · Phase 2

Conditions studied: Extra-Adrenal Paraganglioma, Metastatic Adrenal Gland Pheochromocytoma, Paraganglioma, Recurrent Adrenal Gland Pheochromocytoma

In brief

This phase II trial studies how well pazopanib hydrochloride works in treating patients with advanced or progressive malignant pheochromocytoma or paraganglioma. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Key facts

Study ID

NCT01340794

Run by

National Cancer Institute (NCI)

People needed

7

Starts

2011-05-01

Expected to finish

2014-11-01

Last updated by the study team

2017-09-21

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically or cytologically confirmed malignant secretory or non-secretory pheochromocytoma or paraganglioma that is unresectable and deemed inappropriate for alternative local regional therapeutic approaches
• Objective evidence of tumor progression =< 185 days prior to registration as assessed by:
• Unequivocal progression of objectively measured disease on successive appropriate imaging (e.g. computed tomography [CT] scan); in cases of uncertainty of tumor progression, the principal investigator of the study will be available to assist in decisions
• Measurable disease defined as:
• At least one non-nodal lesion whose longest diameter can be accurately measured as >= 2.0 cm with chest x-ray, or as >= 1.0 cm with CT scan, CT component of a positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI); and/or
• A lymph node whose short axis must be > 1.5 cm when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm)
• Note: Tumor lesions in a previously irradiated area are not considered measurable disease
• Life expectancy > 24 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Leukocytes >= 3,000/uL
• Absolute neutrophil count >= 1,500/uL
• Platelets >= 100,000/uL
• Hemoglobin >= 9 g/dL (5.6 mmol/L); transfusions not permitted =< 7 days of registration
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (except in cases of Gilbert's syndrome, where indirect bilirubin may be elevated, but the direct bilirubin remains within 1.5 x ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
• NOTE: Subjects who have both bilirubin > ULN and AST/ALT > ULN are not eligible
• Alkaline phosphatase =< 2.5 x ULN
• Creatinine =< 1.5 mg/dL (133 umol/L) or within normal institutional limits OR creatinine clearance >= 50 mL/min/1.73m\^2 for subjects with creatinine levels about institutional normal
• Urine protein/creatinine ratio =< 1 OR 24-hour urine < 1 gram
• Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) =< 1.2 x ULN unless a subject is receiving Coumadin and has stable INR which is in range for the desired level of anticoagulation
• Blood pressure (BP) < 140 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 < 140/90 mmHg
• NOTE: All patients with secretory pheochromocytomas or paragangliomas are required to: 1) be evaluated in consultation by a hypertension specialist (at the registering institution) with 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 2) receive alpha- and beta-adrenergic blockade for at least 7 days prior to initiation of pazopanib (GW786034); the hypertension specialist of record for each patient should be committed to following the patient during the clinical study with evaluation by said specialist required at all run-in cycle evaluations (cycles 1 and 2) and also after the first continuous dosing cycle (cycle 3) and thereafter on an as needed basis
• Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
• Ability to understand and the willingness to sign a written informed consent document
• Willingness to donate blood and tissue for correlative marker studies

You may not qualify if…

• Any of the following:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception NOTE: breastfeeding should be discontinued if the mother is treated with pazopanib (GW786034)
• Any of the following:
• Chemotherapy/systemic therapy =< 4 weeks prior to registration
• Radiotherapy =< 4 weeks prior to registration
• Surgery =< 4 weeks prior to registration
• Nitrosoureas or mitomycin C =< 6 weeks prior to registration
• Those who have not recovered from adverse events due to agents administered more than 4 weeks earlier 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
• Any other ongoing investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib (GW786034) or other agents used in the study
• Any of the following:
• Corrected QT (QTc) prolongation (defined as a QTc interval >= 500 msecs)
• Left ventricular ejection fraction (LVEF) < institutional lower limit of normal (LLN)
• Frequent ventricular ectopy
• Evidence of ongoing myocardial ischemia
• Receiving prohibited cytochrome P450 (CYP) interactive concomitant medications within 7 days prior to registration
• Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain pazopanib (GW786034)
• Receiving any medications or substances with risk of torsades de pointes; note: medications or substances with risk of torsades de pointes are prohibited; medications or substances with possible or conditional risk of torsades de pointes may be used while on study with extreme caution and careful monitoring; patients receiving these later cautionary agents must be monitored serially with electrocardiogram (ECG) weekly during the run-in and first cycle of therapy and at each evaluation thereafter NOTE: These medications should be discontinued or replaced with drugs that do not carry these risks, if possible
• Any of the following conditions:
• Active peptic ulcer disease
• Known intraluminal bowel metastatic lesions
• Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation

Where it is running

• Mayo Clinic in Arizona — Scottsdale, Arizona, United States
• Mayo Clinic in Florida — Jacksonville, Florida, United States
• Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore, Maryland, United States
• University of Michigan Comprehensive Cancer Center — Ann Arbor, Michigan, United States
• Mayo Clinic — Rochester, Minnesota, United States
• Metro-Minnesota NCI Community Oncology Research Program — Saint Louis Park, Minnesota, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• M D Anderson Cancer Center — Houston, Texas, United States
• University of Wisconsin Hospital and Clinics — Madison, Wisconsin, United States
• Chinese University of Hong Kong-Prince of Wales Hospital — Shatin, Hong Kong
• National University Hospital Singapore — Singapore, Singapore

Full record on ClinicalTrials.gov

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