Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00625846
Recruitment Status : Active, not recruiting
First Posted : February 28, 2008
Last Update Posted : March 5, 2018
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial studies the side effects and how well pazopanib hydrochloride works in treating patients with advanced thyroid cancer. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by stopping blood flow to the tumor.

Condition or disease Intervention/treatment Phase
Recurrent Thyroid Gland Carcinoma Stage III Differentiated Thyroid Gland Carcinoma AJCC v7 Stage III Thyroid Gland Medullary Carcinoma AJCC v7 Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v7 Stage IVA Thyroid Gland Medullary Carcinoma AJCC v7 Stage IVA Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7 Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7 Stage IVB Thyroid Gland Medullary Carcinoma AJCC v7 Stage IVB Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7 Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7 Stage IVC Thyroid Gland Medullary Carcinoma AJCC v7 Stage IVC Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7 Thyroid Gland Undifferentiated (Anaplastic) Carcinoma Other: Laboratory Biomarker Analysis Drug: Pazopanib Hydrochloride Phase 2

Detailed Description:


I. To establish the safety and efficacy of GW786034 (pazopanib hydrochloride) as a therapeutic in patients afflicted with differentiated, medullary and anaplastic thyroid cancers.


I. Assessment of the impact of therapy with GW786034 on serum/plasma vascular endothelial growth factor (VEGF) levels.

II. To explore the potential relationship between changes in thyroglobulin levels and tumor response in patients with advanced differentiated thyroid cancer known to be thyroglobulin antibody negative.


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

After completion of study treatment, patients are followed up for 6 months or until 3 years after registration.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 188 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of GW 786034 (Pazopanib) in Advanced Thyroid Cancer
Actual Study Start Date : February 22, 2008
Estimated Primary Completion Date : January 17, 2019

Arm Intervention/treatment
Experimental: Treatment (pazopanib hydrochloride)
Patients receive pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Pazopanib Hydrochloride
Given PO
Other Names:
  • GW786034B
  • Votrient

Primary Outcome Measures :
  1. Proportion of patients who have achieved an objective response to the study agent [ Time Frame: Up to 3 years ]
    Objective response as assessed by Response Evaluation Criteria in Solid Tumors criteria.

  2. Confirmed tumor response (differentiated thyroid cancer expanded cohort) [ Time Frame: Up to 3 years ]
    Tumor response (complete or partial response) as assessed by Response Evaluation Criteria in Solid Tumors criteria noted as objective status on 2 consecutive evaluations at least 8 weeks apart for patients with differentiated thyroid cancer who are thyroglobulin antibody negative.

Secondary Outcome Measures :
  1. Proportion of patients with differentiated thyroid cancer and medullary thyroid cancer who have not failed treatment at 6 months (3 months for anaplastic thyroid cancer) [ Time Frame: Up to 6 months ]
    The proportion of patients who have not failed treatment due to disease progression, adverse reactions, refusal for further participation, or who went on to alternate therapy at 6 months (3 months for anaplastic thyroid cancer patients) will be calculated and summarized independently within each of the patient groups. Assuming that the incidence of response is binomially distributed, 90% binomial confidence intervals will also be calculated.

  2. Proportion of patients in which the radioactive iodine scan have changed from "no uptake" to "any uptake" [ Time Frame: At 6 months (at 3 months for patients with anaplastic thyroid cancer) ]
    The proportion of patients will be calculated.

  3. Proportion of patients achieving a biochemical response in appropriate tumor markers [ Time Frame: Up to 3 years ]
    Levels of free VEGF and PDGF will be explored in a graphical manner in pre-treatment and multiple on-treatment samples.

  4. Incidence of toxicity [ Time Frame: Up to 3 years ]
    Toxicity will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

  5. Overall survival [ Time Frame: Time from registration to date of last follow-up or death due to any cause, assessed up to 3 years ]
    Estimated using the method of Kaplan-Meier.

  6. Times to progression [ Time Frame: Time from registration to the date of progression or last follow-up, whichever comes first, assessed up to 3 years ]
    Time to progression will be estimated using the method of Kaplan-Meier. In addition, the 6-month progression-free rate will be evaluated using the 6-month rates and associated confidence intervals. Competing risk analyses may be done to evaluate time to progression, allowing for going on to alternate treatment or death prior to progression as competing risks.

  7. Time to treatment failure [ Time Frame: Time from registration to the date the patient discontinues treatment, assessed up to 3 years ]
    Estimated using the method of Kaplan-Meier.

  8. Time to subsequent therapy [ Time Frame: Up to 3 years ]
    Estimated using the method of Kaplan-Meier.

  9. Duration of response [ Time Frame: From the date of documentation of partial or complete response until the date of progression or last follow-up (whichever comes first) in the subset of patients with confirmed response, assessed up to 3 years ]
    Duration of response will be assessed.

  10. Biomarker-based response [ Time Frame: Up to 3 years ]
    Rates will be summarized assuming they are binomially distributed, and the biomarker levels themselves will be explored both quantitatively and graphically before and after treatment

Other Outcome Measures:
  1. Change in blood markers for angiogenesis [ Time Frame: Baseline to up to 3 years ]
    Blood markers for angiogenesis including levels of free VEGF, free GW786034, and GW786034/VEGF complexes will be evaluated before and during therapy. Changes in these levels will largely be explored in a graphical manner as well as exploring any potential relationships between these levels and clinical outcome such as response or progression-free rate and toxicity incidence.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically or cytologically confirmed differentiated, medullary or anaplastic thyroid cancer that is now advanced or metastatic; NOTE: patients with thyroid lymphomas or sarcomas are specifically excluded, as are patients with metastatic disease from other sites of origin to thyroid
  • Patients with confirmed differentiated thyroid cancer to be enrolled in the expanded/additional differentiated thyroid cancer (DTC) cohort must be thyroglobulin antibody negative
  • Zero, one or two prior therapeutic regimens (this includes cytotoxic plus non-cytotoxic therapeutic regimens)
  • Absence of sensitivity to therapeutic radioiodine (differentiated only)
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan; NOTE: disease that is measurable by physical examination only is not eligible
  • Life expectancy > 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 (Karnofsky >= 60%)
  • Leukocytes > 3,000/mcL
  • Absolute neutrophil count > 1,500/mcL
  • Platelets > 100,000/mcL
  • Total bilirubin =< 1.5 X institutional upper limit of normal (ULN) (if there is reason to believe that the patient has Gilbert's syndrome, the bilirubin can be fractionated; if the fractionated bilirubin is consistent with Gilbert's syndrome and there is no other possible explanation for the elevated indirect bilirubin, the patient may be eligible for the study if and only if the direct bilirubin is =< 1.5 X institutional ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) < 2.5 X institutional ULN
  • Creatinine =< 1.5 X ULN
  • Proteinuria =< + on urinalysis (may re-check)
  • International normalized ratio (INR) =< 1.2 X the ULN
  • 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
  • Objective evidence of tumor progression in the 6 month period prior to GW786034 initiation as assessed by:

    • Unequivocal progression of objectively measured disease on successive appropriate imaging (e.g. CT scan); in cases of uncertainty of tumor progression, the Principal Investigator of the study will be available to assist in decisions
  • Women of child-bearing potential must have a negative serum pregnancy test =< 7 days prior to registration; NOTE: women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; effective contraception is required for all fertile participants in the trial
  • Ability to understand and the willingness to sign a written informed consent document
  • Willingness to comply with the requirement of the study
  • Willingness to donate blood for correlative marker studies; (only applicable to sites within the United States)

Exclusion Criteria:

  • Anaplastic, differentiated, medullary: a total of > 2 prior therapeutic regimens (this total includes cytotoxic plus non-cytotoxic regimens); Note: enrollment of anaplastic, differentiated, and medullary patients who have had zero, one or two prior therapeutic regimens (cytotoxic plus non-cytotoxic regimens) is allowed - provided therapy ceased > 21 days prior to registration;

    • NOTE: the principal investigator of the study should be contacted in the event of uncertainty related patient eligibility based upon prior therapies
  • Disease that is measurable by physical examination only
  • Any of the following:

    • Radiotherapy =< 4 weeks prior to registration
    • Major surgery =< 4 weeks prior to registration
    • Radiotherapy to >= 25% of bone marrow
    • Concurrent therapy with octreotide unless tumor progression on this therapy has been demonstrated
  • Any other ongoing investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW786034 (pazopanib) or other agents used in the study
  • > +1 proteinuria (< 30 mg/dL) on two consecutive dipstick or other urine assessments taken at least 1 week apart; NOTE: (in cases where questions arise related to disparate proteinuria measurements, the study principal investivator [PI] should be consulted for assistance in determining patient study eligibility)
  • Corrected QT interval (QTc) prolongation (defined as a QTc interval >= 480 msecs) or other significant electrocardiogram (ECG) abnormalities (e.g. frequent ventricular ectopy, evidence of ongoing myocardial ischemia); NOTE: the principal investigator of the study should be contacted in the event of uncertainty related patient eligibility based upon ECG changes
  • Receiving cytochrome P450 (CYP) interactive concomitant medications; certain medications that act through the CYP450 system are specifically prohibited in patients receiving GW786034 (pazopanib) because in vitro data indicate that the agent has the potential to interact with the cytochrome P450 isoenzymes cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) and cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); certain other agents should be used with caution
  • Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain GSK786034 (pazopanib)
  • Any of the following conditions:

    • Serious or non-healing wound, ulcer, or bone fracture
    • History of abdominal fistula, gastrointestinal perforation, active diverticulitis, intra-abdominal abscess or gastrointestinal tract bleeding =< 28 days of registration
    • Any history of cerebrovascular accident (CVA) =< 6 months
    • Current use of therapeutic warfarin; Note: low molecular weight heparin and prophylactic low-dose warfarin (INR < 1.2 X ULN) are permitted; prothrombin time (PT)/partial thromboplastin time (PTT) must meet the inclusion criteria
    • History of myocardial infarction, cardiac arrhythmia, admission for unstable angina, cardiac angioplasty or stenting within the last 12 weeks
    • History of venous thrombosis in last 12 weeks
    • Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; NOTE: a patient who has a history of class II heart failure and is asymptomatic on treatment may be considered eligible
    • History of bleeding disorder, including patients afflicted with hemophilia, disseminated intravascular coagulation, or any other abnormality of coagulation potentially predisposing patients to bleeding
    • Poorly controlled depression or anxiety disorder, or recent (=< 6 months) suicidal ideation
  • Known active and/or untreated brain metastases and/or brain metastases requiring ongoing therapy (e.g. corticosteroids); NOTE: (because of the poor prognosis often associated with brain metastases and because of the potential risk of bleeding in active brain metastases associated with multi-targeted tyrosine kinase inhibitor therapy, patients with active and/or untreated brain metastases and/or those with brain metastases requiring ongoing therapy - e.g. corticosteroids - are excluded from trial enrollment; enrollment will, however, be permitted in cases of patients with longstanding treated and inactive brain metastases not requiring ongoing therapy, providing that stability of brain metastases has been demonstrated for a period of 3 months or greater as assessed by intracranial imaging - and providing that there is no indication of increased vascularity of the treated metastases by magnetic resonance imaging (MRI) imaging conducted =< 14 days prior to registration; when questions arise related to these criteria, the PI of the trial, Dr. Keith Bible, should be contacted for assistance on eligibility)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would or might reasonably be expected to limit compliance with study requirements
  • Pregnant women; NOTE: (breastfeeding should be discontinued if the mother is treated with GW786034/pazopanib)
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy; NOTE: (appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated)
  • Receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of GW786034 (pazopanib); NOTE: the eligibility of patients will be determined following review of their case by the Principal Investigator; efforts should be made to switch patients who are taking enzyme-inducing anticonvulsant agents to other medications
  • Receiving any concomitant medications that are associated with a risk of QTc prolongation and/or Torsades de Pointes; NOTE: these medications should be discontinued or replaced with drugs that do not carry these risks, if possible

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00625846

United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Iowa
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
United States, Michigan
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
Fairview Ridges Hospital
Burnsville, Minnesota, United States, 55337
Fairview-Southdale Hospital
Edina, Minnesota, United States, 55435
Unity Hospital
Fridley, Minnesota, United States, 55432
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, United States, 55109
Abbott-Northwestern Hospital
Minneapolis, Minnesota, United States, 55407
Mayo Clinic
Rochester, Minnesota, United States, 55905
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, United States, 55416
United Hospital
Saint Paul, Minnesota, United States, 55102
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Australia, Western Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia, 6009
China, Hong Kong
Chinese University of Hong Kong-Prince of Wales Hospital
Shatin, Hong Kong, China
National University Hospital Singapore
Singapore, Singapore, 119074
National Cancer Centre
Singapore, Singapore, 169610
Johns Hopkins Singapore
Singapore, Singapore, 308433
National Taiwan University Hospital
Taipei, Taiwan, 100
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Keith Bible Mayo Clinic

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI) Identifier: NCT00625846     History of Changes
Obsolete Identifiers: NCT01648387, NCT02653053
Other Study ID Numbers: NCI-2009-00198
NCI-2009-00198 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
7627 ( Other Identifier: Mayo Clinic )
7627 ( Other Identifier: CTEP )
N01CM00099 ( U.S. NIH Grant/Contract )
N01CM62205 ( U.S. NIH Grant/Contract )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: February 28, 2008    Key Record Dates
Last Update Posted: March 5, 2018
Last Verified: January 2018

Additional relevant MeSH terms:
Thyroid Diseases
Thyroid Neoplasms
Carcinoma, Medullary
Carcinoma, Neuroendocrine
Thyroid Carcinoma, Anaplastic
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Ductal, Lobular, and Medullary
Neoplasms, Nerve Tissue