Clinical trial NCT00559949: Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine
Official title: Phase 2 Study of Selumetinib Hydrogen Sulfate in Iodine-131 Refractory Papillary Thyroid Carcinoma and Papillary Thyroid Carcinoma With Follicular Elements
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-11-19
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Median Progression-Free Survival (PFS)
timeFrame: Up to 2 years
measure: Occurrence of Treatment Related Adverse Events
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: David Neil Hayes
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hayes DN, Lucas AS, Tanvetyanon T, Krzyzanowska MK, Chung CH, Murphy BA, Gilbert J, Mehra R, Moore DT, Sheikh A, Hoskins J, Hayward MC, Zhao N, O'Connor W, Weck KE, Cohen RB, Cohen EE. Phase II efficacy and pharmacogenomic study of Selumetinib (AZD6244; ARRY-142886) in iodine-131 refractory papillary thyroid carcinoma with or without follicular elements. Clin Cancer Res. 2012 Apr 1;18(7):2056-65. doi: 10.1158/1078-0432.CCR-11-0563. Epub 2012 Jan 12.