AZD6244 in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine

This study has been completed.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: November 16, 2007
Last updated: September 2, 2016
Last verified: September 2016
This phase II trial is studying how well AZD6244 works in treating patients with papillary thyroid cancer that did not respond to radioactive iodine. AZD6244 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition Intervention Phase
Recurrent Thyroid Gland Carcinoma
Stage I Thyroid Gland Papillary Carcinoma
Stage II Thyroid Gland Papillary Carcinoma
Stage III Thyroid Gland Papillary Carcinoma
Stage IV Thyroid Gland Papillary Carcinoma
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Drug: Selumetinib
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of AZD6244 Hydrogen Sulfate in Iodine-131 Refractory Papillary Thyroid Carcinoma and Papillary Thyroid Carcinoma With Follicular Elements

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Objective response rate (complete response and partial response) [ Time Frame: Up to 2 years ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 2 years ]
    Will be reported using the Kaplan- Meier method with associated confidence intervals.

  • Progression-free survival [ Time Frame: From start of treatment to time of progression or death, assessed up to 2 years ]
    Will be reported using the Kaplan-Meier method stratified by quartiles of pERK.

  • Toxicity assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 2 years ]
    Toxicities will be reported as proportions with associated confidence intervals.

Enrollment: 39
Study Start Date: December 2007
Study Completion Date: August 2016
Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral AZD6244 twice daily on days 1-28. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study Drug: Selumetinib
Given orally
Other Names:
  • ARRY-142886
  • AZD6244
  • MEK Inhibitor AZD6244

Detailed Description:


I. Ascertain the objective response rate (complete response and partial response) in patients with iodine I 131-refractory papillary thyroid cancer treated with AZD6244.


I. Determine the toxicity of this treatment in these patients. II. Determine the pharmacokinetic profile of this treatment in these patients. III. Determine the progression-free and overall survival of these patients. IV. Assess proxy measures of treatment response (thyroglobulin and PET scan) in patients treated with AZD6244.

IV. Compare relevant laboratory correlates between responders and non-responders.

OUTLINE: This is a multicenter study.

Patients receive oral AZD6244 twice daily on days 1-28. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression.

Archived tissue is examined for gene mutations, including RET, BRAF, NTRK, and RAS, by fluorescence in situ hybridization and/or polymerase chain reaction and fluorescence melting curve analysis. Protein expression of ERK and phosphorylated ERK is assessed by immunohistochemical staining.

Blood samples are collected periodically for pharmacokinetic analysis and biomarker assessment (thyroglobulin and antithyroglobulin autoantibodies).

After completion of study therapy, patients are followed periodically for up to 2 years.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically or cytologically confirmed papillary thyroid cancer or papillary thyroid cancer with follicular elements
  • No longer amenable to radioactive iodine therapy or curative surgical resection

    • Tumor is no longer iodine avid
    • Tumor did not respond to the most recent radioactive iodine treatment
    • Patient is ineligible for further radioactive iodine therapy due to medical contraindications (e.g., lung toxicity)
  • 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 CT scan
  • Evidence of disease progression (objective growth of existing tumors)

    • New or enlarging measurable lesions within the past 12 months
    • If the most recent imaging study is older than 12 months, patients will still be eligible if objectively measurable disease progression is associated with clinical symptoms
  • Archival tumor tissue available for mutational analysis
  • No known brain metastases
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 12 weeks
  • WBC ≥ 3,000/µL
  • ANC ≥ 1,500/µL
  • Platelet count ≥ 100,000/µL
  • Total bilirubin normal
  • AST and ALT < 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to, during, and for 4 weeks after completion of study treatment
  • Able to understand and willing to sign a written informed consent document
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244 or its excipient Captisol®
  • QTc interval > 450 msec or other factors that increase the risk of QT prolongation
  • Arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome), including heart failure that meets NYHA class III and IV definition
  • Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
  • Concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
  • At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • Prior treatment with tyrosine kinase inhibitors that target RET or RAF
  • Prior treatment with MEK inhibitors
  • Concurrent combination antiretroviral therapy for HIV-positive patients
  • Concurrent medication that can prolong the QT interval
  • Other concurrent investigational agents
  Contacts and Locations
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Please refer to this study by its identifier: NCT00559949

United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
United States, North Carolina
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27599
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Tennessee
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Canada, Ontario
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: David Hayes Moffitt Cancer Center
  More Information

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00559949     History of Changes
Obsolete Identifiers: NCT00589940
Other Study ID Numbers: NCI-2009-01056  NCI-2009-01056  LOI 7918  CDR0000574262  LOI 7918  7918  N01CM62201  N01CM62203  N01CM62208  P30CA076292 
Study First Received: November 16, 2007
Last Updated: September 2, 2016

Additional relevant MeSH terms:
Thyroid Diseases
Carcinoma, Papillary
Thyroid Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Endocrine System Diseases
Neoplasms, Squamous Cell
Endocrine Gland Neoplasms
Neoplasms by Site
Head and Neck Neoplasms processed this record on January 19, 2017