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Recurrent Thyroid Gland CarcinomaPhase 2NCT00625846

Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer

A Phase 2 study testing Laboratory Biomarker Analysis and Pazopanib Hydrochloride in people with Recurrent Thyroid Gland Carcinoma and Stage III Differentiated Thyroid Gland Carcinoma AJCC v7, run by National Cancer Institute (NCI) at 22 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 19 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
152 participants
Where
22 sitesin 5 countries
Study dates
22 Feb 2008to 13 Aug 2019
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 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 22Show fewer
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 (Karnofsky >= 60%)
  • Leukocytes > 3,000/mcL obtained =< 7 days prior to registration
  • Absolute neutrophil count > 1,500/mcL obtained =< 7 days prior to registration
  • Platelets > 100,000/mcL obtained =< 7 days prior to registration
  • Total bilirubin =< 1.5 X institutional upper limit of normal (ULN) obtained =< 7 days prior to registration (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 obtained =< 7 days prior to registration
  • Creatinine =< 1.5 X ULN obtained =< 7 days prior to registration
  • Proteinuria =< + on urinalysis (may re-check) obtained =< 7 days prior to registration
  • International normalized ratio (INR) =< 1.2 X the ULN obtained =< 7 days prior to registration
  • 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)

Who cannot join

  • 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
Show all 30Show fewer
  • 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 investigator [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

Trial locations and contacts

22 sites in 5 countries.

22 sites in 5 countries

United States16 sites

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Fairview-Southdale Hospital

    Edina, Minnesota, 55435

  • Unity Hospital

    Fridley, Minnesota, 55432

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Minnesota Oncology Hematology PA-Maplewood

    Maplewood, Minnesota, 55109

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

Singapore3 sites

  • National University Hospital Singapore

    Singapore, 119074

  • National Cancer Centre

    Singapore, 169610

  • Johns Hopkins Singapore

    Singapore, 308433

Other trials in Singapore

Australia1 site

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

Other trials in Australia

China1 site

  • Chinese University of Hong Kong-Prince of Wales Hospital

    Shatin, Hong Kong

Other trials in China

Taiwan1 site

  • National Taiwan University Hospital

    Taipei, 100

Other trials in Taiwan

About this study

Official title: A Phase II Study of GW 786034 (Pazopanib) in Advanced Thyroid Cancer

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.

Read the detailed description

PRIMARY OBJECTIVE:

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

CORRELATIVE OBJECTIVES:

  1. 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.

OUTLINE:

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

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

Being tested
Laboratory Biomarker Analysis, Pazopanib Hydrochloride
Medical subject headings
Thyroid Neoplasms, Carcinoma, Medullary, Thyroid Carcinoma, Anaplastic

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 NCT00625846
Study groupRoleWhat they receive
Cohort 1 (DTC)ExperimentalPatients with differentiated thyroid cancer (DTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Drug: Pazopanib Hydrochloride
Cohort 2 (MTC)ExperimentalPatients with medullary thyroid cancer (MTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Pazopanib Hydrochloride
Cohort 3 (ATC)ExperimentalPatients with anaplastic thyroid cancer (ATC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis
Expansion Cohort (DTC)ExperimentalPatients with confirmed, differentiated thyroid cancer (DTC) who are thyroglobulin antibody negative receive 800 mg pazopanib hydrochloride PO QD on days 1-28. 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. Overall Response Rate (in Cohorts 1-3)

    The tumor response rate is defined as the percentage of eligible patients who fulfill RECIST 1.0 for a complete or partial response at two consecutive assessments at least 8 weeks apart for patients in Cohorts 1-3. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Up to 3 years

  2. Confirmed Tumor Response (in the Differentiated Thyroid Cancer Expansion Cohort)

    The confirmed tumor response rate is defined as the percentage of eligible patients who fulfill RECIST 1.0 for a complete or partial response at two consecutive assessments at least 8 weeks apart for patients with differentiated thyroid cancer who are thyroglobulin antibody negative. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Up to 3 years

Secondary outcomes (3)

  1. Toxicity as Measured by the Percentage of Patients Reporting a Grade 3+ Adverse Event Deemed Possibly, Probably, or Definitely Related to Treatment

    Toxicity (defined as grade 3+ adverse events deemed possibly, probably, or definitely related to treatment) will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. The percentage of patients with grade 3+ adverse events deemed possibly, probably, or definitely related to treatment are reported for patients in Cohorts 1-3.

    Measured: Up to 3 years

  2. Progression-Free Survival at 6 Months (Cohorts 1 and 2 Only)

    Progression free survival at 6 months (PFS6) is defined as the proportion of patients alive and without progression at 6 months. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.

    Measured: Time from registration to the date of progression or last follow-up, whichever comes first, assessed up to 6 months

  3. Progression-Free Survival at 3 Months (Cohort 3 Only)

    Progression free survival at 3 months (PFS6) is defined as the proportion of patients alive and without progression at 3 months. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.

    Measured: Time from registration to the date of progression or last follow-up, whichever comes first, assessed up to 3 months

Timeline

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

  1. First posted28 Feb 2008 (estimated)
  2. Study start22 Feb 2008
  3. Primary completion21 Dec 2018
  4. Study completion13 Aug 2019

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
152 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00625846
Sponsor's protocol ID
NCI-2009-00198
Other IDs
NCI-2009-00198, MC057H, CDR0000588044, 7627, 7627, N01CM00099, N01CM62205, P30CA015083
Status last verified
Feb 2020
First submitted
27 Feb 2008
Last updated
26 Feb 2020
Data monitoring committee
No

Publications

  • Bible KC, Menefee ME, Lin CJ, Millward MJ, Maples WJ, Goh BC, Karlin NJ, Kane MA, Adkins DR, Molina JR, Donehower RC, Lim WT, Flynn PJ, Richardson RL, Traynor AM, Rubin J, LoRusso PM, Smallridge RC, Burton JK, Suman VJ, Kumar A, Voss JS, Rumilla KM, Kipp BR, Chintakuntlawar AV, Harris P, Erlichman C. An International Phase 2 Study of Pazopanib in Progressive and Metastatic Thyroglobulin Antibody Negative Radioactive Iodine Refractory Differentiated Thyroid Cancer. Thyroid. 2020 Sep;30(9):1254-1262. doi: 10.1089/thy.2019.0269. Epub 2020 Jul 29.

    PubMed 32538690

  • Bible KC, Suman VJ, Molina JR, Smallridge RC, Maples WJ, Menefee ME, Rubin J, Sideras K, Morris JC 3rd, McIver B, Burton JK, Webster KP, Bieber C, Traynor AM, Flynn PJ, Goh BC, Tang H, Ivy SP, Erlichman C; Endocrine Malignancies Disease Oriented Group; Mayo Clinic Cancer Center; Mayo Phase 2 Consortium. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol. 2010 Oct;11(10):962-72. doi: 10.1016/S1470-2045(10)70203-5. Epub 2010 Sep 17.

    PubMed 20851682

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis and Pazopanib Hydrochloride in people with Recurrent Thyroid Gland Carcinoma and Stage III Differentiated Thyroid Gland Carcinoma AJCC v7, run by National Cancer Institute (NCI) at 22 sites in 5 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 22 inclusion and 30 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: finished, as of the sponsor's last update on 26 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States, Singapore, Australia, China, Taiwan. 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 26 Feb 2020). 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?

Overall Response Rate (in Cohorts 1-3) (time frame: Up to 3 years). The study lists 2 primary outcomes in all. 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 NCT00625846, which also lists 2 linked publications.

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 26 Feb 2020.

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