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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00559949
First received: November 16, 2007
Last updated: December 2, 2016
Last verified: December 2016
  Purpose
This phase II trial is studying how well selumetinib works in treating patients with papillary thyroid cancer that did not respond to radioactive iodine. Selumetinib 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
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 Selumetinib 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 (ORR) [ Time Frame: Up to 2 years ]
    ORR: Complete Response (CR) and Partial Response (PR) evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. A conservative estimate of the response rate of the best-studied agent in this disease, doxorubicin, is approximately 5%. Therefore, investigators will assume that selumetinib (AZD6244, NSC 741078) would be worth further pursuit if the response rate (CR+PR) were at least 20%.


Secondary Outcome Measures:
  • Median Progression-Free Survival (PFS) [ Time Frame: Up to 2 years ]
    PFS is defined as the duration of time from start of treatment to time of progression or death. Progression evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive Disease (PD): 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm. Secondary end points include toxicity, progression free survival, and overall survival. Due to the small sample size and absence of high quality historic data for this disease, these analyses were planned to be mostly exploratory and descriptive in nature.

  • Occurrence of Treatment Related Adverse Events [ Time Frame: Up to 2 years ]
    Number of participants with related adverse events, per category and Grade category. Toxicity assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  • Overall Survival (OS) [ Time Frame: Up to 2 years ]
    Overall Survival using the Kaplan-Meier method with associated confidence intervals. OS analysis was intended to be mostly exploratory and descriptive in nature.


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 selumetinib 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
Drug: Selumetinib
Selumetinib was administered orally as a free base suspension at a dose of 100 mg twice daily for 28-day cycles. Those participants experiencing Common Terminology Criteria for Adverse Events (CTCAE) v3.0 grade 3 toxicity or worse had their dose reduced to 50 mg twice daily and then to 50 mg once daily, if necessary.
Other Names:
  • ARRY-142886
  • AZD6244
  • MEK Inhibitor AZD6244

Detailed Description:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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 selumetinib.

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

OUTLINE: This is a multicenter study.

Patients receive oral selumetinib 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.

  Eligibility

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

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 selumetinib (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 ClinicalTrials.gov identifier: NCT00559949

Locations
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)
Investigators
Principal Investigator: David Neil Hayes UNC Lineberger Comprehensive Cancer Center
  More Information

Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00559949     History of Changes
Obsolete Identifiers: NCT00589940
Other Study ID Numbers: NCI-2009-01056
NCI-2009-01056 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
LOI 7918
CDR0000574262
LOI 7918 ( Other Identifier: Moffitt Cancer Center )
7918 ( Other Identifier: CTEP )
N01CM62201 ( US NIH Grant/Contract Award Number )
N01CM62203 ( US NIH Grant/Contract Award Number )
N01CM62208 ( US NIH Grant/Contract Award Number )
P30CA076292 ( US NIH Grant/Contract Award Number )
Study First Received: November 16, 2007
Results First Received: December 2, 2016
Last Updated: December 2, 2016

Additional relevant MeSH terms:
Carcinoma
Thyroid Diseases
Thyroid Neoplasms
Carcinoma, Papillary
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Neoplasms, Squamous Cell

ClinicalTrials.gov processed this record on April 28, 2017