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Metastatic Thyroid Gland CarcinomaPhase 2NCT02393690

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

A Phase 2 study testing Iodine I-131 and Selumetinib in people with Metastatic Thyroid Gland Carcinoma and Poorly Differentiated Thyroid Gland Carcinoma, run by Academic and Community Cancer Research United at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial studies how well iodine I-131 works with or without selumetinib in treating patients with thyroid cancer that has returned (recurrent) or has spread from where it started to other places in the body (metastatic). Many thyroid cancers absorb iodine. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Iodine I-131 and Selumetinib
Type of treatment
Surgery or procedure
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
11 sitesUnited States
Study dates
4 May 2015to 31 Dec 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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,
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  • 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
  • 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 (obtained =< 28 days prior to randomization)
  • 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

Who cannot join

  • 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
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  • 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. (NOTE: Performance of investigational 124I PET/CT scans is allowed prior to and during conduct of this study)
  • 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

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Hoag Memorial Hospital

    Newport Beach, California, 92663

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

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

This phase II trial studies how well iodine I-131 works with or without selumetinib in treating patients with thyroid cancer that has returned (recurrent) or has spread from where it started to other places in the body (metastatic). 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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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.

CORRELATIVE OBJECTIVE:

  1. 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.

Being tested
Iodine I-131, Placebo Administration, Selumetinib
Medical subject headings
Thyroid Neoplasms, Adenocarcinoma, Follicular, Thyroid Cancer, Papillary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Iodine I-131Radiation

    Also called 131-Iodine, Bound Iodide I-131, I 131, I-131

    Given PO

  • Placebo AdministrationOther

    Given PO

  • SelumetinibDrug

    Also called ARRY-142886, AZD6244, MEK Inhibitor AZD6244

    Given PO

Study groups in NCT02393690
Study groupRoleWhat they receive
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.
Receives: Radiation: Iodine I-131; Drug: 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.
Receives: Radiation: Iodine I-131; Other: Placebo Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Response at 6 Months

    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). A Complete Response (CR) is defined as the disappearance of all target lesions and thyroglobulin measured to be less than 0.2 ng/ml. A Partial Response (PR) is defined as at least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the long or short axis of all the target lymph nodes (depending on which axis is being used for assessments) at current evaluation) taking as reference the baseline sum of dimensions (BSD).

    >

    > A patient will be classified as a responder if they have a partial or complete response at the 6-month time point. The proportion of patients with a response will be calculated and compared between the 2 Arms using a Fisher's Exact test.

    Measured: At 6 months

Secondary outcomes (4)

  1. Overall Response Rate

    The best overall response rate will be compared between the two arms. This comparison will be done using a Fisher exact 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.

    Measured: 2 years

  2. Progression Free Survival (PFS)

    PFS will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.

    Measured: 2 years

  3. Changes in Serum Thyroglobulin Levels

    Changes in serum thyroglobulin levels will be compared between the 2 treatment arms by 6 month response using the Wilcoxon Rank-Sum test.

    Measured: 6 months

  4. Incidence of Adverse Events

    The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The number and percentage of patients experiencing grade 3+ adverse events will be compared between the 2 treatment arms.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Mar 2015 (estimated)
  2. Study start4 May 2015
  3. Primary completion17 Jul 2020
  4. Study completion31 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02393690
Sponsor's protocol ID
RU241306I
Other IDs
NCI-2015-00277, 14-008494, RU241306I, P30CA015083
Status last verified
Jun 2024
First submitted
16 Mar 2015
Last updated
26 Jul 2024
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Iodine I-131 and Selumetinib in people with Metastatic Thyroid Gland Carcinoma and Poorly Differentiated Thyroid Gland Carcinoma, run by Academic and Community Cancer Research United at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response at 6 Months (time frame: At 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02393690.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2024.

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