Clinical Trial: Cediranib Maleate With or Without Lenalidomide in Treating Patients With Thyroid Cancer

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase I/II Trial of Cediranib Alone or Cediranib and Lenalidomide in Iodine 131-Refractory Differentiated Thyroid Cancer

Brief Summary: This partially randomized phase I/II trial studies the side effects and best dose of cediranib maleate when given together with or without lenalidomide and to see how well they work in treating patients with thyroid cancer. Cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of thyroid cancer by blocking blood flow to the tumor. It is not yet known whether cediranib maleate is more effective when given together with lenalidomide in treating thyroid cancer.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of cediranib (cediranib maleate) plus lenalidomide. (Phase I) II. Determine the progression-free survival rates of single agent cediranib in patients with iodine refractory, unresectable differentiated thyroid cancer (DTC) who have evidence of disease progression within 12 months of study enrollment. (Phase II) III. Determine the progression-free survival rates of cediranib in combination with lenalidomide in patients with iodine refractory, unresectable DTC who have evidence of disease progression within 12 months of study enrollment. (Phase II) IV. Compare the progression-free survival curves of single agent cediranib to combination therapy with cediranib with lenalidomide. (Phase II)

SECONDARY OBJECTIVES:

I. Determine the response rate of cediranib in combination with lenalidomide in patients with iodine refractory, unresectable DTC who have evidence of disease progression within 12 months of study enrollment. (Phase I) II. Determine the toxicity, duration of response, progression free survival, and overall survival in patients with DTC treated with cediranib plus lenalidomide. (Phase I) III. Determine response rates and duration of response, early tumor size changes, the toxicity, and overall survival in patients with DTC treated with cediranib or cediranib plus lenalidomide. (Phase II) IV. Determine whether the presence of v-raf murine sarcoma viral oncogene homolog B1 (B-RAF) or V-Ki-ras2 Kirsten rat sarcoma (K-RAS) mutations in patients with DTC predict response to cediranib or cediranib plus lenalidomide. (Phase II)

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Phase I:
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

• Maximum-tolerated dose defined as the highest dose level such that < 2 of 6 patients experience dose-limiting toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I) [ Time Frame: 28 days ]
• Progression-free survival (PFS) (Phase II) [ Time Frame: From start of treatment to time of progression or death of any cause, assessed up to 3 years ]
  Kaplan-Meier curves will be generated for each treatment arm and the median PFS times estimated using the Brookmeyer and Crowley method. In addition to the logrank test, PFS in the two groups will be analyzed by fitting a Cox proportional hazards regression model, adjusting for prior VEGF inhibitor use, performance status, and other baseline risk factors. The goodness of fit of the Cox model and the appropriate functional form for continuous covariates will be assessed using graphical techniques, including inspection of martingale residual plots.

Original Primary Outcome:

• Maximum-tolerated dose (Phase I)
• Response rate (Phase II)

Current Secondary Outcome:

• Adverse events as assessed by NCI CTCAE version 4.0 [ Time Frame: Up to 5 years ]
  Adverse events will be summarized by type and grade. Adverse event rates will be compared between the two treatment groups using a chi square test for common toxicities and Fisher's exact test for less frequent events.
• Objective response rate (Phase I) [ Time Frame: 6 months ]
• Overall survival (OS) [ Time Frame: Up to 5 years ]
  Estimated using the Kaplan-Meier method and compared between groups using the logrank test.
• Percent change in tumor size (Phase II) [ Time Frame: From baseline to 2 months ]
  The percent change in tumor size from baseline to the end of cycle 2 (two months) will be compared between the two groups using a two-sample t test. The post-treatment total sum of lengths for a patient with a new lesion will be scored as 1.2*max(pre-sum, post-sum) to ensure that the appearance of new lesions corresponds to a disease progression per RECIST criteria. In the event of any early deaths prior to two months, a nonparametric rank sum test will be used in place of the t test, with deaths ranked at the extreme end of the distribution.
• Presence or absence of B-RAF and RAS mutations [ Time Frame: Baseline ]
  Present or absent, of B-RAF and RAS mutations will be correlated with response rates using Fisher's exact test, and with PFS and OS by fitting a Cox proportional hazards regression model.
• Response rate (Phase II) [ Time Frame: Up to 5 years ]
  Response rates will be compared using a chi-square test followed by logistic regression analysis to adjust for covariates.
• Serial measurements of TSH and thyroglobulin [ Time Frame: Up to 5 years ]
  Repeated measures analysis of variance (RM ANOVA) will be performed to determine the effect of the treatments on serial measurements of TSH and thyroglobulin.

Original Secondary Outcome:

• Objective response rate, duration of response, progression-free survival, and overall survival (Phase I)
• Toxicity (Phase I)
• Progression-free survival and overall survival (Phase II)

Dates:
Date Received: September 22, 2010
Date Started: September 2010
Date Completion:
Last Updated: May 23, 2017
Last Verified: May 2017