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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01340794
• Date of registration: 21/04/2011
• Prospective Registration: Yes
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Pazopanib Hydrochloride in Treating Patients With Advanced or Progressive Malignant Pheochromocytoma or Paraganglioma
• Scientific title: A Phase 2 Study of Pazopanib (GW786034) in Patients With Advanced and Progressive Malignant Pheochromocytoma or Paraganglioma
• Date of first enrolment: May 2011
• Target sample size: 7
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01340794
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

China, Hong Kong, Singapore, United States

Contacts

• Name: Keith Bible
• Affiliation: Mayo Clinic Cancer Center P2C

Key inclusion & exclusion 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

- 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

Exclusion Criteria:

- 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 monitor


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Metastatic Adrenal Gland Pheochromocytoma

Paraganglioma

Extra-Adrenal Paraganglioma

Recurrent Adrenal Gland Pheochromocytoma

Intervention(s)

Drug: Pazopanib Hydrochloride

Other: Laboratory Biomarker Analysis

Primary Outcome(s)

Response Rate (RR) (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.1 [Time Frame: Up to 5 years]

Secondary Outcome(s)

Overall Survival Time [Time Frame: The time from registration to death due to any cause, assessed up to 5 years]

Duration of Tumor Response [Time Frame: Up to 5 years]

Progression-free Survival Time [Time Frame: The time from registration to documentation of disease progression or death, whichever occurs first, assessed up to 5 years]

Time to Treatment Failure [Time Frame: Up to 5 years from registration]

Secondary ID(s)

8783

N01CM62205

MAYO-MC107B

N01CM00039

NCI-2011-02588

CDR0000699430

MC107B

N01CM00099

P30CA015083

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 21/07/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01340794