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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00559949
First received: November 16, 2007
Last updated: August 19, 2014
Last verified: March 2014
  Purpose

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 Cancer
Stage I Papillary Thyroid Cancer
Stage II Papillary Thyroid Cancer
Stage III Papillary Thyroid Cancer
Stage IV Papillary Thyroid Cancer
Drug: selumetinib
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
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 ] [ Designated as safety issue: No ]

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

  • Progression-free survival [ Time Frame: From start of treatment to time of progression or death, assessed up to 2 years ] [ Designated as safety issue: No ]
    Will be reported using the Kaplan-Meier method stratified by quartiles of pERK.

  • Overall survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Will be reported using the Kaplan- Meier method with associated confidence intervals.


Estimated Enrollment: 32
Study Start Date: December 2007
Estimated Primary Completion Date: April 2018 (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.
Drug: selumetinib
Given orally
Other Names:
  • ARRY-142886
  • AZD6244
Other: pharmacological study
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

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 AZD6244.

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 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.

  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 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
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: NCT00559949

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Canada, Ontario
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Investigators
Principal Investigator: David Hayes H. Lee Moffitt Cancer Center and Research Institute
  More Information

No publications provided

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, CDR0000574262, LOI 7918, 7918, N01CM62203, P30CA076292, N01CM62201, N01CM62208
Study First Received: November 16, 2007
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 21, 2014