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

NCT02393690 | Completed Phase 2 Results DMC

• 4 other identifiers: RU241306INCI-2015-0027714-008494P30CA015083
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 11

Brief 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. 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.

Conditions

Metastatic Thyroid Gland Carcinoma; Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7

Outcome Measures

Primary Outcomes (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.

  At 6 months

Secondary Outcomes (4)

• Overall Response Rate

  2 years

• Progression Free Survival (PFS)

  2 years

• Changes in Serum Thyroglobulin Levels

  6 months

• Incidence of Adverse Events

  2 years

Other Outcomes (1)

• Genomic and Transcriptomic Landscape of Radioactive Iodine-avid (RAIA) Tumors

  Baseline

Study Arms (2)

Arm I (selumetinib, iodine I-131)

EXPERIMENTAL

Patients 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.

Radiation: Iodine I-131; Drug: Selumetinib

Arm II (placebo, iodine I-131)

ACTIVE COMPARATOR

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.

Radiation: Iodine I-131; Other: Placebo Administration

Interventions

Iodine I-131 RADIATION

Given PO

Also known as: 131-Iodine, Bound Iodide I-131, I 131, I-131, Iodide I-131, Iodide, I-131, Iodine 131, Iodotope, Iodotrope

Arm I (selumetinib, iodine I-131); Arm II (placebo, iodine I-131)

Placebo Administration OTHER

Given PO

Arm II (placebo, iodine I-131)

Selumetinib DRUG

Given PO

Also known as: ARRY-142886, AZD6244, MEK Inhibitor AZD6244

Arm I (selumetinib, iodine I-131)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• I 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

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (11)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Hoag Memorial Hospital

Newport Beach, California, 92663, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Thyroid Neoplasms; Adenocarcinoma, Follicular; Thyroid Cancer, Papillary

Interventions

Iodine-131; AZD 6244

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Adenocarcinoma, Papillary

Results Point of Contact

• Title: Alan Ho, M.D.
• Organization: Academic and Community Cancer Research United (ACCRU)

hoa@mskcc.org

212-639-7202

Study Officials

• Alan L Ho

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2015
• First Posted: March 19, 2015
• Study Start: May 4, 2015
• Primary Completion: July 17, 2020
• Study Completion: December 31, 2023
• Last Updated: July 26, 2024
• Results First Posted: August 3, 2021

Record last verified: 2024-06

Locations

US (11)