Clinical Trial: Iodine I 131 and Pazopanib Hydrochloride in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer Previously Treated With Iodine I 131 That Cannot Be Removed By Surgery

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I Clinical Trial of Pazopanib in Combination With Escalating Doses of Radioactive 131I in Patients With Well-Differentiated Thyroid Carcinoma Refractory to Radioiodine, Despite Having Some Upt

Brief Summary: This phase I trial is studying the side effects and best dose of iodine I 131 when given together with pazopanib hydrochloride in treating patients with recurrent and/or metastatic thyroid cancer previously treated with iodine I 131 that cannot be removed by surgery. Radioactive drugs, such as iodine I 131, may carry radiation directly to cancer cells and not harm normal cells. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving iodine I 131 together with pazopanib hydrochloride may be an effective treatment for thyroid cancer.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the safety, tolerability and feasibility of administrating escalating doses of 131I (iodine I 131) in combination with concurrent pazopanib (pazopanib hydrochloride) therapy in order to define the maximum tolerated dose (MTD)/recommended phase II dose (RP2D) in patients with radioiodine (RAI)-refractory disease with minor RAI-uptake.

SECONDARY OBJECTIVES:

I. To determine the effects of pazopanib in combination with 131I on RAI-avidity, uptake and tumor response rate (Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1).

II. To determine the time to tumor progression (TTP) or recurrence (progression will be determined by RECIST criteria and by increases in suppressed thyroglobulin levels > 50% as compared to tumor imaging and suppressed thyroglobulin levels performed within 1 week of the last dose of pazopanib).

OUTLINE: This is a dose-escalation study of iodine I 131.

Patients receive iodine I 131 intramuscularly (IM) once daily (QD) 5 days a week in weeks 5-6. Patients also receive pazopanib hydrochloride orally (PO) QD beginning in week 1 and continuing for 8 weeks post-radioactive iodine therapy.

After completion of study treatment, patients are followed up at 28 days.


Sponsor: University of Washington

Current Primary Outcome: Toxicity and the occurrence of dose limiting toxicity (DLT) when pazopanib is given in conjunction with radioiodine to establish the MTD and RP2D in combination [ Time Frame: 8 weeks post radioactive iodine administration ]

Assessment of adverse events will include type, incidence, severity (graded by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], Version 4.03), timing, seriousness, and relatedness; and laboratory abnormalities. Descriptive statistics will be calculated for all variables and responses; continuous data will be expressed as their mean +/- standard deviation, median and range, and categorical data will be listed by frequency of occurrence and proportion of total (with 95% confidence intervals) for all enrolled patients and by dose cohort.


Original Primary Outcome: Toxicity and the occurrence of dose limiting toxicity (DLT) when pazopanib is given in conjunction with radioiodine to establish the MTD and RP2D in combination [ Time Frame: 8 weeks post radioactive iodine administration ]

Toxicities will be classified by NCI common toxicity criteria. Descriptive statistics will be calculated for all variables and responses; continuous data will be expressed as their mean ± standard deviation, median and range, and categorical data will be listed by frequency of occurrence and proportion of total (with 95% confidence intervals) for all enrolled patients and by dose cohort.


Current Secondary Outcome:

  • Tumor response [ Time Frame: At week 14 ]
    Assessed using RECIST criteria. Tumor response will be compared to responses and duration of TTP after last prior historical RAI treatment.
  • TTP [ Time Frame: At week 14 ]
    TTP will be compared to responses and duration of TTP after last prior historical RAI treatment.


Original Secondary Outcome:

  • Tumor response [ Time Frame: At week 14+ ]
  • TTP [ Time Frame: At week 14+ ]
  • Radioiodine uptake by thyroid tissue as assessed by whole body imaging and dosimetric calculations using a low dose of 2 to 5 mCi 131I [ Time Frame: Baseline and 28 days post treatment ]
  • Tumor perfusion, flow dynamics, and response as assessed by dynamic fluorodeoxyglucose positron emission tomography (FDG-PET) [ Time Frame: Baseline and days 22-28 ]


Information By: University of Washington

Dates:
Date Received: July 20, 2011
Date Started: December 2011
Date Completion:
Last Updated: November 4, 2015
Last Verified: November 2015