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

Recurrent Thyroid Gland Carcinoma Clinical Trial

Official title:

Phase 2 Study of AZD6244 Hydrogen Sulfate in Iodine-131 Refractory Papillary Thyroid Carcinoma and Papillary Thyroid Carcinoma With Follicular Elements

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00559949
• Other study ID #: NCI-2009-01056
• Secondary ID: NCI-2009-01056LO
• Status: Completed
• Phase: Phase 2
• First received: November 16, 2007
• Last updated: September 2, 2016
• Start date: December 2007
• Est. completion date: August 2016

Study information

• Verified date: September 2016
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00589940

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• 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
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Pharmacological Study

Drug:
• Selumetinib
Given orally

Locations

Country	Name	City	State
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (complete response and partial response)		Up to 2 years	No
Secondary	Overall survival	Will be reported using the Kaplan- Meier method with associated confidence intervals.	Up to 2 years	No
Secondary	Progression-free survival	Will be reported using the Kaplan-Meier method stratified by quartiles of pERK.	From start of treatment to time of progression or death, assessed up to 2 years	No
Secondary	Toxicity assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0	Toxicities will be reported as proportions with associated confidence intervals.	Up to 2 years	Yes