Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine
Condition: 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
MeSH terms: Carcinoma; Thyroid Neoplasms; Carcinoma, Papillary; Thyroid Cancer, Papillary; Thyroid Diseases
Intervention: Laboratory Biomarker Analysis; Selumetinib
Intervention description: Correlative studies; 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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