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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief Summary: This randomized phase II trial studies how well iodine I-131works 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. Because of 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 Summary:

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
Sponsor: Academic and Community Cancer Research United

Current Primary Outcome: Response rate [ Time Frame: 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). 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 6-month progression free survival (PFS) [ Time Frame: Time from study entry to the first of either disease progression or death from any cause, assessed at 6 months ]
    PFS will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.
  • Best overall response [ Time Frame: Up to 2 years ]
    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.
  • Changes in serum thyroglobulin levels [ Time Frame: Baseline to up to 2 years ]
    Baseline serum thyroglobulin levels will be compared between the 2 treatment arms using the Wilcoxon Rank-Sum test.
  • Incidence of adverse events [ Time Frame: Up to 2 years ]
    The maximum grade for each type of adverse event will be summarized using 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.


Original Secondary Outcome:

  • Best overall response [ Time Frame: Up to 2 years ]
    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.
  • 6-month progression free survival (PFS) [ Time Frame: Time from study entry to the first of either disease progression or death from any cause, assessed at 6 months ]
    PFS will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.
  • Changes in serum thyroglobulin levels [ Time Frame: Baseline to up to 2 years ]
    Baseline serum thyroglobulin levels will be compared between the 2 treatment arms using the Wilcoxon Rank-Sum test.
  • Adverse event rate [ Time Frame: Up to 2 years ]
    The maximum grade for each type of adverse event will be summarized using 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.


Information By: Academic and Community Cancer Research United

Dates:
Date Received: March 16, 2015
Date Started: May 2015
Date Completion: August 2020
Last Updated: March 15, 2017
Last Verified: March 2017