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Extra-Adrenal ParagangliomaPhase 2NCT01340794

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

A Phase 2 study testing Laboratory Biomarker Analysis and Pazopanib Hydrochloride in people with Extra-Adrenal Paraganglioma and Metastatic Adrenal Gland Pheochromocytoma, run by National Cancer Institute (NCI) at 11 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis and Pazopanib Hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
11 sitesin 3 countries
Study dates
May 2011to Nov 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
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  • 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
  • History of new abdominal fistula, gastrointestinal perforation or intra-abdominal abscess =< 84 days prior to registration; 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 =< 185 days prior to registration:
  • Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
  • Cardiac arrhythmia
  • Admission for unstable angina
  • 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 < 42 days
  • Arterial thrombosis
  • Symptomatic peripheral vascular disease
  • Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
  • Hemoptysis in excess of 2.5 mL (1/2 teaspoon) =< 60 days prior to registration
  • Any of the following:
  • Known active and/or untreated brain metastases
  • Brain metastases requiring ongoing therapy (e.g. corticosteroids)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy
  • Require heparin other than low-molecular weight heparin
  • Prior use of pazopanib (GW786034)

Trial locations and contacts

11 sites in 3 countries.

11 sites in 3 countries

United States9 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Metro-Minnesota NCI Community Oncology Research Program

    Saint Louis Park, Minnesota, 55416

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

Hong Kong1 site

  • Chinese University of Hong Kong-Prince of Wales Hospital

    Shatin, OX1 3UJ

Other trials in Hong Kong

Singapore1 site

  • National University Hospital Singapore

    Singapore, 119074

Other trials in Singapore

About this study

Official title: A Phase 2 Study of Pazopanib (GW786034) in Patients With Advanced and Progressive Malignant Pheochromocytoma or Paraganglioma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the anti-tumor activity (in terms of the tumor response rate using the Response Evaluation Criteria in Solid Tumors [RECIST] criteria) of pazopanib (pazopanib hydrochloride) (GW786034) in patients with advanced malignant pheochromocytomas and paragangliomas.

SECONDARY OBJEC TIVES:

  1. To assess safety profile of pazopanib. II. To assess duration of tumor response. III. To assess time to treatment failure. IV. To assess progression-free survival time. V. To assess overall survival time.

TERTIARY OBJECTIVES:

  1. For patients with secretory tumors, to examine changes in urinary catecholamine and/or metanephrine levels.

II. For patients with secretory tumors, to examine whether pazopanib-induced changes in urinary catecholamine and/or metanephrine levels during the first cycle of treatment may be associated with objective tumor response.

III. To examine associations between tumor response and somatic mutational status in archived tumors, or germline mutational status in patient's peripheral blood mononuclear cells, (presence of succinate dehydrogenase complex subunit D [SDHD], succinate dehydrogenase complex subunit B [SDHB], ret proto-oncogene [RET], von Hippel-Lindau tumor suppressor [VHL], neurofibromatosis type-1).

IV. To examine associations between tumor response and tumor expression levels of angiogenic and vascular markers including hypoxia inducible factor 1, alpha (HIF-1a), vascular endothelial growth factor receptor (VEGF-R) (total and phospho-) and microvessel density in archival tumor tissue.

IV. To examine whether the extent of tumor response/regression may be correlated with plasma pazopanib (GW786034) concentration achieved after the third cycle (first cycle after run-in cycles) of pazopanib (GW786034) therapy.

OUTLINE:

Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28 (days 1-14 of courses 1 and 2). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo urine and blood sample collection at baseline and periodically during study for correlative studies.

After completion of study therapy, patients are followed up every 3-6 months for up to 5 years.

Being tested
Laboratory Biomarker Analysis, Pazopanib Hydrochloride
Medical subject headings
Paraganglioma, Extra-Adrenal, Pheochromocytoma, Paraganglioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pazopanib HydrochlorideDrug

    Also called GW786034B, Votrient

    Given PO

Study groups in NCT01340794
Study groupRoleWhat they receive
Treatment (pazopanib hydrochloride)ExperimentalPatients receive pazopanib hydrochloride PO QD on days 1-28 (days 1-14 of courses 1 and 2). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Drug: Pazopanib Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Response Rate (RR) (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.1

    Response and progression are evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1) Ninety-five percent confidence intervals for the true response proportion was calculated using the exact binomial test.

    Complete Response (CR): All of the following must be true:

    1. Disappearance of all target and non-target lesions.
    2. Each lymph node must have reduction in short axis to <1.0 cm.

    Partial Response (PR):

    At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking baseline measures as reference.

    Overall Response (OR) was calculated by summing the number of patients with a CR or PR.

    Measured: Up to 5 years

Secondary outcomes (4)

  1. Duration of Tumor Response

    Defined for all patients whose tumor met the criteria of CR or PR (using the RECIST criteria) as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented.

    Measured: Up to 5 years

  2. Overall Survival Time

    Overall survival time is defined as the time from registration to death due to any cause and will be estimated using the Kaplan-Meier method.

    Measured: The time from registration to death due to any cause, assessed up to 5 years

  3. Progression-free Survival Time

    Progression-free survival is defined as the time from registration to documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. Progression-free survival time will be estimated using the Kaplan-Meier method.

    Measured: The time from registration to documentation of disease progression or death, whichever occurs first, assessed up to 5 years

  4. Time to Treatment Failure

    The time from the date of registration to the date at which the patient is removed from treatment due to progression, toxicity, or refusal, assessed up to 5 years.

    Measured: Up to 5 years from registration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2011 (estimated)
  2. Study startMay 2011
  3. Primary completionNov 2014
  4. Study completionNov 2014

Why it stopped: Slow Accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01340794
Sponsor's protocol ID
NCI-2011-02588
Other IDs
NCI-2011-02588, CDR0000699430, MAYO-MC107B, MC107B, 8783, N01CM00039, N01CM00099, N01CM62205
Status last verified
Sep 2017
First submitted
21 Apr 2011
Last updated
21 Sep 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis and Pazopanib Hydrochloride in people with Extra-Adrenal Paraganglioma and Metastatic Adrenal Gland Pheochromocytoma, run by National Cancer Institute (NCI) at 11 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 46 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Hong Kong, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response Rate (RR) (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.1 (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01340794.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2017; AzTrials last refreshed its copy on 7 Nov 2026.

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