Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer

NCT ID: NCT00625846

Last Updated: 2020-02-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 152 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-22
• Study Completion Date: 2019-08-13

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.

Detailed Description

PRIMARY OBJECTIVE:

I. 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:

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. 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.

Conditions

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 Anaplastic Carcinoma AJCC v7; Stage IVA Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVB Thyroid Gland Anaplastic Carcinoma AJCC v7; Stage IVB Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVC Thyroid Gland Anaplastic Carcinoma AJCC v7; Stage IVC Thyroid Gland Medullary Carcinoma AJCC v7; Thyroid Gland Anaplastic Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Pazopanib Hydrochloride

Intervention Type: DRUG

Given PO

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.

Group Type: EXPERIMENTAL

Pazopanib Hydrochloride

Intervention Type: DRUG

Given PO

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.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

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.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Pazopanib Hydrochloride

Intervention Type: DRUG

Given PO

Interventions

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Pazopanib Hydrochloride

Given PO

Intervention Type: DRUG

Other Intervention Names

GW786034B; Votrient

Eligibility Criteria

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)

• 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

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

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Keith C Bible

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

University of Colorado Hospital

Aurora, Colorado, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Fairview Ridges Hospital

Burnsville, Minnesota, United States

Fairview-Southdale Hospital

Edina, Minnesota, United States

Unity Hospital

Fridley, Minnesota, United States

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota, United States

Abbott-Northwestern Hospital

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, United States

United Hospital

Saint Paul, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Chinese University of Hong Kong-Prince of Wales Hospital

Shatin, Hong Kong, China

National University Hospital Singapore

Singapore, , Singapore

National Cancer Centre

Singapore, , Singapore

Johns Hopkins Singapore

Singapore, , Singapore

National Taiwan University Hospital

Taipei, , Taiwan

Countries

United States; Australia; China; Singapore; Taiwan

References

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.

Reference Type: DERIVED

PMID: 32538690 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 20851682 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2009-00198

Identifier Type: REGISTRY

Identifier Source: secondary_id

MC057H

Identifier Type: -

Identifier Source: secondary_id

CDR0000588044

Identifier Type: -

Identifier Source: secondary_id

7627

Identifier Type: OTHER

Identifier Source: secondary_id

7627

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM00099

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62205

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00198

Identifier Type: -

Identifier Source: org_study_id

NCT01648387

Identifier Type: -

Identifier Source: nct_alias

NCT02653053

Identifier Type: -

Identifier Source: nct_alias