Clinical Trials /

Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer

NCT02393690

Description:

This randomized phase II trial studies how well iodine I-131 works with or without selumetinib in treating patients with thyroid cancer that has returned or has spread from where it started to other places in the body. Many thyroid cancers absorb iodine. Due to this, doctors often give radioactive iodine (iodine I-131) alone to treat thyroid cancer as part of standard practice. It is thought that the more thyroid tumors are able to absorb radioactive iodine, the more likely it is that the radioactive iodine will cause those tumors to shrink. Selumetinib may help radioactive iodine work better in patients whose tumors still absorb radioactive iodine. It is not yet known whether iodine I-131 is more effective with or without selumetinib in treating thyroid cancer.

Related Conditions:
  • Thyroid Gland Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer
  • Official Title: Randomized Double-Blind Phase II Study of Radioactive Iodine (RAI) in Combination With Placebo or Selumetinib for the Treatment of RAI-Avid Recurrent/Metastatic Thyroid Cancers

Clinical Trial IDs

  • ORG STUDY ID: RU241306I
  • SECONDARY ID: NCI-2015-00277
  • SECONDARY ID: 14-008494
  • SECONDARY ID: RU241306I
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT02393690

Conditions

  • Metastatic Thyroid Gland Carcinoma
  • Poorly Differentiated Thyroid Gland Carcinoma
  • Recurrent Thyroid Gland Carcinoma
  • Stage IV Thyroid Gland Follicular Carcinoma
  • Stage IV Thyroid Gland Papillary Carcinoma
  • Stage IVA Thyroid Gland Follicular Carcinoma
  • Stage IVA Thyroid Gland Papillary Carcinoma
  • Stage IVB Thyroid Gland Follicular Carcinoma
  • Stage IVB Thyroid Gland Papillary Carcinoma
  • Stage IVC Thyroid Gland Follicular Carcinoma
  • Stage IVC Thyroid Gland Papillary Carcinoma

Interventions

DrugSynonymsArms
SelumetinibARRY-142886, AZD6244, MEK Inhibitor AZD6244Arm I (selumetinib, iodine I-131)

Purpose

This randomized phase II trial studies how well iodine I-131 works with or without selumetinib in treating patients with thyroid cancer that has returned or has spread from where it started to other places in the body. Many thyroid cancers absorb iodine. Due to this, doctors often give radioactive iodine (iodine I-131) alone to treat thyroid cancer as part of standard practice. It is thought that the more thyroid tumors are able to absorb radioactive iodine, the more likely it is that the radioactive iodine will cause those tumors to shrink. Selumetinib may help radioactive iodine work better in patients whose tumors still absorb radioactive iodine. It is not yet known whether iodine I-131 is more effective with or without selumetinib in treating thyroid cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the response rate at 6 months following treatment with 131I (iodine I-131) in
      combination with placebo or selumetinib for radioactive iodine-avid (RAIA) recurrent and/or
      metastatic thyroid cancer.

      SECONDARY OBJECTIVES:

      I. To determine the best overall response following treatment with 131I in combination with
      placebo or selumetinib for RAIA recurrent and/or metastatic thyroid cancer.

      II. To compare the progression-free survival of patients with RAIA recurrent and/or
      metastatic thyroid cancer treated with 131I in combination with placebo or selumetinib.

      III. To compare serum thyroglobulin changes for patients with RAIA recurrent and/or
      metastatic thyroid cancer treated with 131I in combination with placebo or selumetinib.

      IV. To evaluate the safety and tolerability of 131I in combination with placebo or
      selumetinib for patients with RAI-avid recurrent and/or metastatic thyroid cancer.

      TERTIARY OBJECTIVES:

      I. To explore the genomic and transcriptomic landscape of RAIA tumors for signatures that
      correlate to therapeutic benefit achieved with 131I in combination with placebo or
      selumetinib.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive selumetinib orally (PO) twice daily (BID) starting on week 1, day 1
      and continuing through 2 days after iodine I-131 therapy has been administered. Approximately
      3 weeks after beginning treatment with selumetinib, patients receive iodine I-131 PO.

      ARM II: Patients receive placebo PO BID starting on week 1, day 1 and continuing through 2
      days after iodine I-131 therapy has been administered. Approximately 3 weeks after beginning
      treatment with placebo, patients receive iodine I-131 PO.

      After completion of study treatment, patients are followed up at 1 and 3 months, every 3
      months for 12 months, and then every 6 months for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (selumetinib, iodine I-131)ExperimentalPatients receive selumetinib PO BID starting on week 1, day 1 and continuing through 2 days after iodine I 131 therapy has been administered. Approximately 3 weeks after beginning treatment with selumetinib, patients receive iodine I-131 PO.
  • Selumetinib
Arm II (placebo, iodine I-131)Active ComparatorPatients receive placebo PO BID starting on week 1, day 1 and continuing through 2 days after iodine I-131 therapy has been administered. Approximately 3 weeks after beginning treatment with placebo, patients receive iodine I-131 PO.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Diagnosis of recurrent and/or metastatic thyroid cancer
    
              -  Histological or cytological confirmation of thyroid carcinoma of follicular origin
                 (including papillary, follicular, or poorly differentiated subtypes and their
                 respective variants); NOTE: medullary and anaplastic thyroid cancers are excluded;
                 Hurthle cell carcinomas are excluded (defined as having an invasive tumor composed of
                 > 75% oncocytic [Hurthle] cells lacking the nuclear features of papillary carcinoma,
                 tumor necrosis, and marked mitotic activity); patients with oncocytic (Hurthle cell)
                 variants of papillary thyroid carcinoma (defined as a tumor composed of a majority of
                 oncocytic [Hurthle] cells having the nuclear features of papillary carcinoma) are
                 eligible to participate
    
              -  RAI-avid lesion on a radioiodine scan (a diagnostic, post-therapy, or post-ablation
                 scans) performed =< 24 months prior to registration, which suggests that therapy with
                 131I is justifiable in the judgment of the investigator
    
              -  Clinically or radiographically evident structural disease; patients with measurable
                 disease and those with only non-measurable (?non-target?) structural disease
                 (according to modified Response Evaluation Criteria in Solid Tumors [RECIST] version
                 [v] 1.1 criteria) are eligible;
    
            NOTE 1: Modification of the RECIST v1.1 measurable disease criteria includes a change in
            the definition of what is considered a measurable malignant lymph node; a malignant lymph
            node is considered measurable if any of the following apply:
    
              -  It is noted to be RAI-avid on radioactive iodine imaging (diagnostic or post-therapy
                 whole body scans acceptable) and it measures >= 1 cm in the long axis,
    
              -  It is pathologically proven to be involved with thyroid cancer (by cytology or
                 pathology) and it measures >= 1 cm in the long axis, or
    
              -  Its short axis is >= 1.5 cm when assessed by computed tomography (CT) scan NOTE 2:
                 Patients only with biochemical evidence of disease without structural evidence of
                 cancer are not eligible for this study
    
                   -  For patients with non-measurable, structural disease the following must apply:
    
              -  Undetectable thyroglobulin antibody AND
    
              -  A serum thyroglobulin of 10 ng/ml or greater in the context of suppressed
                 thyroid-stimulating hormone (TSH) (TSH =< 0.4 mcU/ml) =< 28 days prior to study
                 registration; use of any thyroglobulin assay is allowed, though all serum
                 thyroglobulin measurements for study purposes must be conducted with the same
                 thyroglobulin assay
    
                   -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
    
                   -  Able to swallow and retain orally-administered medication with no clinically
                      significant gastrointestinal abnormalities that may alter absorption
    
                   -  Obtained =< 28 days prior to randomization:
    
            Absolute neutrophil count (ANC) >= 1500/mm^3
    
              -  Obtained =< 28 days prior to randomization:
    
            Platelet count >= 100,000/mm^3
    
              -  Obtained =< 28 days prior to randomization:
    
            Hemoglobin > 9.0 g/dL
    
              -  Obtained =< 28 days prior to randomization:
    
            Total bilirubin =< 1.5 x upper limit of normal (ULN)
    
              -  Obtained =< 28 days prior to randomization:
    
            Aspartate transaminase (AST) =< 2.5 x ULN (or =< 5 x ULN in presence of liver metastases)
    
              -  Obtained =< 28 days prior to randomization:
    
            Creatinine =< 1.5 mg/dL OR calculated creatinine clearance of >= 50 ml/min by either the
            Cockcroft-Gault formula or 24-hours urine collection analysis
    
              -  Negative pregnancy test performed =< 7 days prior to registration for women of
                 childbearing potential only
    
              -  Provide informed written consent
    
              -  Willing to return to enrolling institution for follow-up (during the Active Monitoring
                 Phase of the study)
    
                   -  Note: during the Active Monitoring Phase of a study (i.e., active treatment and
                      observation), participants must be willing to return to the consenting
                      institution for follow-up
    
              -  Willing to provide mandatory archival tumor tissue (block or minimum of 30 unstained
                 slides from a primary or recurrent/metastatic thyroid cancer) for correlative research
                 purposes; NOTE: patients with less archival tumor tissue available may still be
                 eligible for the study after discussion with Academic and Community Cancer Research
                 United (ACCRU); receipt of archival tumor tissue is not required for study
                 registration and initiation of therapy
    
              -  Willing to provide mandatory blood samples for correlative research purposes
    
            Exclusion Criteria:
    
              -  131I therapy =< 6 months prior to registration; Note: 131I administered solely for
                 diagnostic purposes is not considered 131I therapy
    
              -  External beam radiation therapy =< 28 days prior to registration; note: previous
                 treatment with radiation is allowed if the investigator judges it will not compromise
                 patient safety on the study
    
              -  Having been treated with a total cumulative (lifetime) 131I therapeutic activity > 800
                 mCi (excluding 131I activity administered for diagnostic scans)
    
              -  Treatment with chemotherapy or targeted therapy (e.g. tyrosine kinase inhibitor) =< 28
                 days prior to registration
    
              -  Prior exposure to mitogen-activated protein kinase kinase (MEK), RAS, or RAF
                 inhibitors (note: previous exposure to sorafenib is allowed) OR history of
                 hypersensitivity to selumetinib, thyrotropin alpha (Thyrogen), or any excipient agents
    
              -  Unresolved toxicity > Common Terminology Criteria for Adverse Events (CTCAE) grade 2
                 from previous anti-cancer therapy, except for alopecia
    
              -  Cardiac conditions as follows:
    
                   -  Uncontrolled hypertension (blood pressure [BP] >=150/95 mmHg despite medical
                      therapy)
    
                   -  Left ventricular ejection fraction < 55% measured by echocardiography
    
                   -  Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on
                      electrocardiogram (ECG) at rest
    
                   -  Symptomatic heart failure (New York Heart Association [NYHA] grade II-IV)
    
                   -  Prior or current cardiomyopathy
    
                   -  Severe valvular heart disease
    
                   -  Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical
                      therapy)
    
                   -  Acute coronary syndrome =< 6 months prior to registration
    
              -  Ophthalmological conditions as follows:
    
                   -  Intra-ocular pressure > 21 mmHg, or uncontrolled glaucoma (irrespective of
                      intra-ocular pressure)
    
                   -  Current or past history of central serous retinopathy or retinal vein occlusion
    
              -  Symptomatic or untreated leptomeningeal disease, brain metastasis, or spinal cord
                 compression
    
              -  Unable to follow a low iodine diet or requiring medication with high content in iodide
                 (e.g., amiodarone)
    
              -  Received iodinated intravenous contrast within =< 2 months of registration; avoidance
                 of iodinated oral contrast is also preferred but not strictly required for study
                 enrollment; NOTE: those who have had iodinated intravenous contrast within this time
                 frame may still be eligible if a urinary iodine analysis reveals that excess iodine
                 has been cleared (defined as urinary iodine documented to be < 300 mcg/day by either a
                 spot urinary iodine or 24-hour urinary iodine measurement)
    
              -  Any of the following:
    
                   -  Pregnant women
    
                   -  Nursing women
    
                   -  Men or women of childbearing potential who are unwilling to employ adequate
                      contraception
    
              -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
                 of the investigator, would make the patient inappropriate for entry into this study or
                 interfere significantly with the proper assessment of safety and toxicity of the
                 prescribed regimens
    
              -  Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
                 positive and currently receiving antiretroviral therapy; NOTE: patients known to be
                 HIV positive, but without clinical evidence of an immunocompromised state, are
                 eligible for this trial
    
              -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
                 infection, hepatitis B infection, hepatitis C infection, symptomatic congestive heart
                 failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
                 situations that would limit compliance with study requirements
    
              -  Receiving any other investigational agent which would be considered as a treatment for
                 the primary neoplasm
    
              -  Other active malignancy =< 2 years prior to registration that will interfere with
                 conduct of this trial; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of
                 the cervix; NOTE: if there is a history of prior malignancy, patients must not be
                 receiving other specific treatment (chemotherapy, hormonal therapy, radiation) for
                 their cancer
    
              -  Not willing to discontinue use of supplemental vitamin E
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Response rate
    Time Frame:At 6 months
    Safety Issue:
    Description:A patient will be classified as a responder if they have a partial or complete response at the 6-month time point when compared to the baseline, pre-study radiologic scan(s). The proportion of patients with a response will be calculated and compared between the 2 arms using a Chi-square or Fisher?s Exact test.

    Secondary Outcome Measures

    Measure:Best overall response
    Time Frame:Up to 2 years
    Safety Issue:
    Description:The best overall response will be compared between the two arms. This comparison will be done using a chi-square test. For a patient to be classified as a response, they need a partial or complete response that is confirmed at least 4 weeks later anytime during the study.
    Measure:Changes in serum thyroglobulin levels
    Time Frame:Baseline to up to 2 years
    Safety Issue:
    Description:Changes in serum thyroglobulin levels will be compared between the 2 treatment arms using the Wilcoxon Rank-Sum test.
    Measure:Incidence of adverse events
    Time Frame:Up to 2 years
    Safety Issue:
    Description:The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The frequency and percentage of grade 3+ adverse events will be compared between the 2 treatment arms. Comparisons between arms will be made by using either the Chi-square or Fisher?s Exact test.
    Measure:Progression free survival (PFS)
    Time Frame:Up to 2 years
    Safety Issue:
    Description:PFS will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Academic and Community Cancer Research United

    Last Updated

    November 8, 2017