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: June 30, 2014
Last verified: December 2013
  Purpose

This phase II trial is studying 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 Intervention Phase
Anaplastic Thyroid Cancer
Recurrent Thyroid Cancer
Stage III Follicular Thyroid Cancer
Stage III Papillary Thyroid Cancer
Stage IV Follicular Thyroid Cancer
Stage IVA Follicular Thyroid Cancer
Stage IVA Papillary Thyroid Cancer
Stage IVB Follicular Thyroid Cancer
Stage IVB Papillary Thyroid Cancer
Stage IVC Follicular Thyroid Cancer
Stage IVC Papillary Thyroid Cancer
Thyroid Gland Medullary Carcinoma
Drug: pazopanib hydrochloride
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of GW 786034 (Pazopanib) in Advanced Thyroid Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of patients who have achieved an objective response to the study agent [ Time Frame: Every 8 weeks and then every 4 weeks, assessed up to 3 years ] [ Designated as safety issue: No ]
    Objective response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria

  • Confirmed tumor response (DTC expanded cohort) [ Time Frame: 2 consecutive evaluations at least 8 weeks apart and then every 4 weeks, assessed 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


Secondary Outcome Measures:
  • 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: At 3 (ATC) and 6 months (DTC and MTC) ] [ 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.

  • 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 achieving a biochemical response in appropriate tumor markers [ Time Frame: At baseline, weeks 1-4 of course 1, retreatment weeks 4, 8, 12, 16, and then at the end of treatment. ] [ 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.

  • Clinical and biologic responses as well as tolerability simultaneously and independently in each patient cohort (differentiated, medullary, and anaplastic thyroid cancer cohorts) [ Time Frame: not ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: Weekly during treatment and at the end of study treatment ] [ 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.

  • Times to progression and death [ 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.

  • Time to treatment failure and time to subsequent therapy [ Time Frame: Time from registration to the date the patient discontinues treatment ] [ Designated as safety issue: No ]
    Distribution will be estimated using the method of Kaplan-Meier. In addition, the time to subsequent therapy will also be evaluated using a similar approach.

  • 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 ] [ Designated as safety issue: No ]
  • Biomarker-based response [ Time Frame: At baseline and after treatment ] [ 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


Estimated Enrollment: 188
Study Start Date: February 2008
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (tyrosine kinase inhibitor therapy)
Patients receive pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: pazopanib hydrochloride
Other Names:
  • GW786034B
  • Votrient
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To establish the safety and efficacy of pazopanib hydrochloride in patients with differentiated, medullary, or anaplastic thyroid cancer.

SECONDARY OBJECTIVES:

I. To assess the impact of pazopanib hydrochloride on serum and plasma 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed thyroid cancer that is now advanced or metastatic disease

    • One of the following subtypes:

      • Differentiated thyroid cancer
      • Absence of sensitivity to therapeutic radioiodine
      • Medullary thyroid cancer
      • Anaplastic thyroid cancer
  • Patients with confirmed differentiated thyroid cancer (DTC) must be thyroglobulin antibody negative to be enrolled in the expanded/additional DTC cohort
  • Zero, one or two prior therapeutic regimens (this includes cytotoxic plus non-cytotoxic therapeutic regimens)
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral computed tomography (CT) scan
  • Objective evidence of tumor progression within the past 6 months, as assessed by the following:

    • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 3 months
  • Leukocytes ≥ 3,000/mcL
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (direct bilirubin ≤ 1.5 times ULN if patient has Gilbert syndrome)
  • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 times ULN
  • Creatinine ≤ 1.5 times ULN
  • Proteinuria ≤ 1+ on urinalysis

    • No proteinuria > 1+ (< 30 mg/dL) on two consecutive dipstick or other urine assessments taken at least 1 week apart
  • International normalized ratio (INR) ≤ 1.2 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to and during study therapy
  • Systolic blood pressure (BP) < 140 mm Hg and diastolic BP < 90 mm Hg

    • Initiation or adjustment of BP medication is permitted prior to registration provided the average of three BP readings at a visit prior to registration is < 140/90 mm Hg
  • No sensitivity to therapeutic radioiodine (differentiated only)
  • Able to understand and willing to sign a written informed consent document
  • Willing to comply with the requirements of the study
  • Willing to donate blood for correlative marker studies (only applicable to sites within the United States)
  • No admission for unstable angina, cardiac angioplasty, or stenting within the past 12 weeks
  • At least 4 weeks since prior radiotherapy
  • At least 4 weeks since prior major surgery
  • No prior surgical procedure affecting absorption
  • No requirement for IV alimentation
  • No prior radiotherapy to ≥ 25% of bone marrow
  • No concurrent octreotide

    • Concurrent octreotide allowed provided tumor progression on this drug has been demonstrated
  • No other concurrent investigational agents
  • No cytochrome (CYP) interactive medications prior to, during, and for at least 1-2 weeks after discontinuation from the study
  • No concurrent antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients
  • No concurrent medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of pazopanib hydrochloride
  • No concurrent investigational or commercial agents or therapies other than those used for this study with the intent to treat the patient's malignancy
  • No concurrent therapeutic warfarin

    • Low molecular weigh the paring and prophylactic low-dose warfarin allowed
  • No more than 2 total prior cytotoxic or noncytotoxic therapeutic regimens

    • Up to two total prior noncytotoxic or cytotoxic therapeutic regimens are allowed provided therapy ceased > 21 days prior to registration
  • No concurrent medications that are associated with a risk of QTc prolongation and/or Torsades de Pointes

Exclusion Criteria:

  • Thyroid lymphomas, sarcomas, or metastatic disease from other sites of origin to thyroid
  • Disease that is measurable by physical examination only
  • Known active and/or untreated brain metastases and/or brain metastases requiring ongoing therapy (e.g., corticosteroids)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib hydrochloride or other agents used in the study
  • QTc prolongation (defined as a QTc interval ≥ 4800 msecs) or other significant electrocardiogram (ECG) abnormalities (e.g., frequent ventricular ectopy or 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
  • Any condition that impairs the ability to swallow and retain pazopanib hydrochloride, including any of the following:

    • Gastrointestinal tract disease resulting in an inability to take oral medication
    • Active peptic ulcer disease
  • Any of the following conditions:

    • Serious or nonhealing wound, ulcer, or bone fracture
    • History of abdominal fistula
    • Gastrointestinal perforation
    • Active diverticulitis
    • Intra-abdominal abscess or gastrointestinal tract bleeding within the past 28 days prior to registration
    • History of cerebrovascular accident (CVA) within the past 6 months
    • History of myocardial infarction, cardiac arrhythmia within the past 12 weeks
    • History of venous thrombosis within the past 12 weeks
    • NYHA class III or IV heart failure
    • History of bleeding disorder including 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00625846

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Colorado
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
University of Colorado
Denver, Colorado, United States, 80217-3364
United States, District of Columbia
Howard University Hospital
Washington, District of Columbia, United States, 20060
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Iowa
University of Iowa Hospitals and Clinics
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
Mayo Clinic
Rochester, Minnesota, United States, 55905
Metro-Minnesota CCOP
Saint Louis Park, Minnesota, United States, 55416
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
CoxHealth South Hospital
Springfield, Missouri, United States, 65807
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
China, Hong Kong
Chinese University of Hong Kong-Prince of Wales Hospital
Shatin, Hong Kong, China, OX1 3UJ
Singapore
National University Hospital
Singapore, Singapore, 119074
National Cancer Centre
Singapore, Singapore, 169610
Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 100
Sponsors and Collaborators
Investigators
Principal Investigator: Keith Bible Mayo Clinic
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00625846     History of Changes
Obsolete Identifiers: NCT01648387
Other Study ID Numbers: NCI-2009-00198, NCI-2009-00198, CDR0000588044, MC057H, 7627, P30CA015083, N01CM00099
Study First Received: February 27, 2008
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 22, 2014