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Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00625846
First received: February 27, 2008
Last updated: August 31, 2016
Last verified: August 2016

February 27, 2008
August 31, 2016
February 2008
June 2017   (final data collection date for primary outcome measure)
  • Confirmed tumor response (DTC expanded cohort) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Tumor response (complete or partial response) as assessed by RECIST criteria noted as objective status on 2 consecutive evaluations at least 8 weeks apart for patients with DTC who are thyroglobulin antibody negative.
  • Proportion of patients who have achieved an objective response to the study agent [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Objective response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Proportion of patients who have achieved an objective response to the study agent as assessed by RECIST criteria [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00625846 on ClinicalTrials.gov Archive Site
  • Biomarker-based response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    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
  • Duration of response [ Time Frame: From the date of documentation of response (PR or CR) 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 ] [ Designated as safety issue: No ]
  • Incidence of toxicity [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Toxicity will be assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 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.
  • Overall survival [ Time Frame: Time from registration to date of last follow-up or death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier.
  • Proportion of patients achieving a biochemical response in appropriate tumor markers [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Levels of free VEGF and PDGF will be explored in a graphical manner in pre-treatment and multiple on-treatment samples.
  • 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 ATC) ] [ Designated as safety issue: No ]
  • Proportion of patients with differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC) who have not failed treatment at 6 months (3 months for anaplastic thyroid cancer [ATC]) [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    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 ATC 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.
  • Time to subsequent therapy [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier.
  • Time to treatment failure [ Time Frame: Time from registration to the date the patient discontinues treatment, assessed up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier.
  • 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 ] [ Designated as safety issue: No ]
    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.
  • Proportion of patients who have not failed treatment at 6 months (3 months for anaplastic thyroid cancer) [ Designated as safety issue: No ]
  • Proportion of patients in which the radioactive iodine scan have changed from "no uptake" to "any uptake" [ Designated as safety issue: No ]
  • Proportion of patients achieving a biochemical response in appropriate tumor markers [ Designated as safety issue: No ]
  • Clinical and biologic responses as well as tolerability simultaneously and independently in each patient cohort (differentiated, medullary, and anaplastic thyroid cancer cohorts) [ Designated as safety issue: Yes ]
  • Toxicity [ Designated as safety issue: Yes ]
Change in blood markers for angiogenesis [ Time Frame: Baseline to up to 3 years ] [ Designated as safety issue: No ]
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.
Not Provided
 
Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer
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.

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Thyroid Gland Carcinoma
  • Stage III Differentiated Thyroid Gland Carcinoma
  • Stage III Thyroid Gland Medullary Carcinoma
  • Stage IVA Differentiated Thyroid Gland Carcinoma
  • Stage IVA Thyroid Gland Medullary Carcinoma
  • Stage IVA Thyroid Gland Undifferentiated (Anaplastic) Carcinoma
  • Stage IVB Differentiated Thyroid Gland Carcinoma
  • Stage IVB Thyroid Gland Medullary Carcinoma
  • Stage IVB Thyroid Gland Undifferentiated (Anaplastic) Carcinoma
  • Stage IVC Differentiated Thyroid Gland Carcinoma
  • Stage IVC Thyroid Gland Medullary Carcinoma
  • Stage IVC Thyroid Gland Undifferentiated (Anaplastic) Carcinoma
  • Thyroid Gland Undifferentiated (Anaplastic) Carcinoma
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Pazopanib Hydrochloride
    Given PO
    Other Names:
    • GW786034B
    • Votrient
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.
Interventions:
  • Other: Laboratory Biomarker Analysis
  • Drug: Pazopanib Hydrochloride
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
188
Not Provided
June 2017   (final data collection date for primary outcome measure)

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 =< 1+ 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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   China,   Singapore,   Taiwan
Korea, Republic of
 
NCT00625846
NCI-2009-00198, NCI-2009-00198, MC057H, CDR0000588044, MC057H, 7627, N01CM00099, N01CM62205, P30CA015083
Yes
Not Provided
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Keith Bible Mayo Clinic
National Cancer Institute (NCI)
August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP