Clinical Trial: Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer

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

Official Title: A Phase 2 Study of Trametinib in Combination With Radioiodine (RAI) for RAS Mutant or RAS/RAF Wild-Type, RAI-Refractory Recurrent, and/or Metastatic Thyroid Cancers

Brief Summary: This phase II trial studies how well trametinib works in increasing tumoral iodine incorporation in patients with thyroid cancer that has come back or spread to another place in the body. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and may help make treatment with iodine I-131 more effective.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate the effect of trametinib on enhancing radioiodine (RAI) activity by determining the proportion of patients alive at 6 months without disease progression by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1) criteria following treatment with RAI in co-administration with trametinib. (Cohort A) II. To evaluate the effect of trametinib on enhancing RAI activity by determining the objective response rate (ORR) at 6 months following treatment with radioiodine (RAI) in co-administration with trametinib. (Cohort A) III. To determine the proportion of patients following trametinib therapy with increased tumoral iodine incorporation as quantified by iodine iodine-124 (I-124) positron emission tomography (PET)/computed tomography (CT) lesional dosimetry. (Cohort B)

SECONDARY OBJECTIVES:

I. To determine the proportion of patients following trametinib therapy with increased tumoral iodine incorporation as quantified with I-124 PET/CT lesional dosimetry. (Cohort A) II. To evaluate the safety/tolerability of trametinib with or without RAI. (Cohort A) III. To evaluate changes in thyroglobulin levels in patients treated with RAI. (Cohort A) IV. To explore potential correlations between genomic alterations present in the tumor and/or tumoral pharmacodynamic changes induced by trametinib to clinical outcomes. (Cohort A) V. To evaluate the effect of trametinib on enhancing RAI activity by determining the ORR at 6 months following treatment with RAI in co-administration with trametinib. (Cohort B) VI. To evaluate the effect of trametinib on enhancing RAI activity by determining the proportion of patients alive at 6 months without disease progression by RECIST v 1.1 criteria following treatment with RAI in co-administration with trametinib
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Iodine incorporation in thyroid cancer metastases to a predicted lesional absorbed radiation dose equal to or exceeding 2,000 cGy with the administration of =< 300 mCi RAI (Cohort B) [ Time Frame: Up to 6 months ]
  • ORR (complete response or partial response) assessed by RECIST v 1.1 (Cohort A) [ Time Frame: At 6 months ]
    An exact binomial stage design will be used to discriminate between true 6-month ORR rates at 6 months of 5% and 25%.
  • Progression free survival (Cohort A) [ Time Frame: At 6 months ]
    An exact binomial stage design will be used to discriminate between true 6-month progression/death rates of 20% vs 50%.
  • Proportion of patients alive following treatment with trametinib and I-124 (Cohort A) [ Time Frame: At 6 months ]


Original Primary Outcome:

  • Proportion of patients alive following treatment with trametinib and I-124 (Cohort A) [ Time Frame: At 6 months ]
  • Progression free survival (Cohort A) [ Time Frame: At 6 months ]
    An exact binomial stage design will be used to discriminate between true 6-month progression/death rates of 20% vs 50%.
  • ORR (complete response or partial response) assessed by RECIST v 1.1 (Cohort A) [ Time Frame: At 6 months ]
    An exact binomial stage design will be used to discriminate between true 6-month ORR rates at 6 months of 5% and 25%.
  • Iodine incorporation in thyroid cancer metastases to a predicted lesional absorbed radiation dose equal to or exceeding 2,000 cGy with the administration of < 300 mCi RAI (Cohort B) [ Time Frame: Up to 6 months ]


Current Secondary Outcome:

  • Adequate increase defined as increasing iodine incorporation in thyroid cancer metastases to a predicted lesional absorbed radiation dose equal to or exceeding 2,000 cGy with the administration of =< 300 mCi RAI (Cohort A) [ Time Frame: Up to 6 months ]
    Proportion of patients with an adequate increase will be reported, along with the corresponding exact 95% confidence interval.
  • Best objective response (Cohort C) [ Time Frame: Up to 6 months ]
    Estimated using 95% confidence intervals.
  • Changes in thyroglobulin [ Time Frame: Baseline to up to 6 months ]
    Wilcoxon signed rank test will be performed for paired samples to compare the thyroglobulin level before and after RAI treatment in the subset of patients treated with RAI.
  • Incidence of toxicity assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Cohort A) [ Time Frame: Up to 30 days after completion of treatment ]
    Toxicities will be individually reported and summarized.
  • ORR per RECIST v 1.1 criteria (Cohort B) [ Time Frame: At 6 months ]
    An exact binomial stage design will be used to discriminate between true 6-month ORR rates at 6 months of 5% and 25%.
  • Proportion of patients alive without disease progression by RECIST v 1.1 criteria (Cohort C) [ Time Frame: At 6 months ]
    Estimated using 95% confidence intervals.
  • Proportion of patients alive without disease progression per RECIST v 1.1(Cohort B) [ Time Frame: At 6 months ]


Original Secondary Outcome:

  • Adequately increase defined as increasing iodine incorporation in thyroid cancer metastases to a predicted lesional absorbed radiation dose equal to or exceeding 2,000 cGy with the administration of < 300 mCi RAI (Cohort A) [ Time Frame: Up to 6 months ]
    Proportion of patients with an adequate increase will be reported, along with the corresponding exact 95% confidence interval.
  • Changes in serum thyroglobulin [ Time Frame: Baseline to up to 6 months ]
    Wilcoxon signed rank test will be performed for paired samples to compare the serum thyroglobulin level before and after RAI treatment in the subset of patients treated with RAI.
  • Incidence of toxicity assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Cohort A) [ Time Frame: Up to 30 days after completion of treatment ]
    Toxicities will be individually reported and summarized.
  • ORR per per RECIST v 1.1 criteria (Cohort B) [ Time Frame: At 6 months ]
    An exact binomial stage design will be used to discriminate between true 6-month ORR rates at 6 months of 5% and 25%.
  • Proportion of patients alive without disease progression per RECIST v 1.1(Cohort B) [ Time Frame: At 6 months ]
  • Proportion of patients alive without disease progression by RECIST v 1.1 criteria (Cohort C) [ Time Frame: At 6 months ]
    Estimated using 95% confidence intervals.
  • Best objective response (Cohort C) [ Time Frame: Up to 6 months ]
    Estimated using 95% confidence intervals.


Information By: National Cancer Institute (NCI)

Dates:
Date Received: May 29, 2014
Date Started: August 2014
Date Completion:
Last Updated: May 23, 2017
Last Verified: May 2017