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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00625846




Registration number
NCT00625846
Ethics application status
Date submitted
27/02/2008
Date registered
28/02/2008
Date last updated
26/02/2020

Titles & IDs
Public title
Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer
Scientific title
A Phase II Study of GW 786034 (Pazopanib) in Advanced Thyroid Cancer
Secondary ID [1] 0 0
NCI-2009-00198
Secondary ID [2] 0 0
NCI-2009-00198
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent Thyroid Gland Carcinoma 0 0
Stage III Differentiated Thyroid Gland Carcinoma AJCC v7 0 0
Stage III Thyroid Gland Medullary Carcinoma AJCC v7 0 0
Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v7 0 0
Stage IVA Thyroid Gland Anaplastic Carcinoma AJCC v7 0 0
Stage IVA Thyroid Gland Medullary Carcinoma AJCC v7 0 0
Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7 0 0
Stage IVB Thyroid Gland Anaplastic Carcinoma AJCC v7 0 0
Stage IVB Thyroid Gland Medullary Carcinoma AJCC v7 0 0
Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7 0 0
Stage IVC Thyroid Gland Anaplastic Carcinoma AJCC v7 0 0
Stage IVC Thyroid Gland Medullary Carcinoma AJCC v7 0 0
Thyroid Gland Anaplastic Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Thyroid
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Pazopanib Hydrochloride

Experimental: Cohort 1 (DTC) - Patients 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.

Experimental: Cohort 2 (MTC) - Patients 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.

Experimental: Cohort 3 (ATC) - Patients 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.

Experimental: Expansion Cohort (DTC) - Patients 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.


Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Pazopanib Hydrochloride
Given PO
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (in Cohorts 1-3)
Timepoint [1] 0 0
Up to 3 years
Primary outcome [2] 0 0
Confirmed Tumor Response (in the Differentiated Thyroid Cancer Expansion Cohort)
Timepoint [2] 0 0
Up to 3 years
Secondary outcome [1] 0 0
Toxicity as Measured by the Percentage of Patients Reporting a Grade 3+ Adverse Event Deemed Possibly, Probably, or Definitely Related to Treatment
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
Progression-Free Survival at 6 Months (Cohorts 1 and 2 Only)
Timepoint [2] 0 0
Time from registration to the date of progression or last follow-up, whichever comes first, assessed up to 6 months
Secondary outcome [3] 0 0
Progression-Free Survival at 3 Months (Cohort 3 Only)
Timepoint [3] 0 0
Time from registration to the date of progression or last follow-up, whichever comes first, assessed up to 3 months

Eligibility
Key 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 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)
Minimum age
19 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/02/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/08/2019
Sample size
Target
Accrual to date
Final
152
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
Wisconsin
Country [10] 0 0
China
State/province [10] 0 0
Hong Kong
Country [11] 0 0
Singapore
State/province [11] 0 0
Singapore
Country [12] 0 0
Taiwan
State/province [12] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Keith C Bible
Address 0 0
Mayo Clinic
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00625846