Cediranib Maleate With or Without Lenalidomide in Treating Patients With Thyroid Cancer
This partially randomized phase I/II trial is studying 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.
Recurrent Thyroid Cancer
Stage I Follicular Thyroid Cancer
Stage I Papillary Thyroid Cancer
Stage II Follicular Thyroid Cancer
Stage II Papillary Thyroid Cancer
Stage III Follicular Thyroid Cancer
Stage III Papillary Thyroid Cancer
Stage IVA Follicular Thyroid Cancer
Stage IVA Papillary Thyroid Cancer
Stage IVB Follicular Thyroid Cancer
Stage IVB Papillary Thyroid Cancer
Stage IVC Follicular Thyroid Cancer
Stage IVC Papillary Thyroid Cancer
Drug: cediranib maleate
Other: laboratory biomarker analysis
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Trial of Cediranib Alone or Cediranib and Lenalidomide in Iodine 131-Refractory Differentiated Thyroid Cancer|
- 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 ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: No ]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.
- Objective response rate (Phase I) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Overall survival (OS) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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.
- Adverse events as assessed by NCI CTCAE version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]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.
- Serial measurements of TSH and thyroglobulin [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Repeated measures analysis of variance (RM ANOVA) will be performed to determine the effect of the treatments on serial measurements of TSH and thyroglobulin.
- Presence or absence of B-RAF and RAS mutations [ Time Frame: At baseline ] [ Designated as safety issue: No ]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.
|Study Start Date:||September 2010|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Arm A (cediranib maleate)
Patients receive cediranib maleate PO QD on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Drug: cediranib maleate
Other Names:Other: laboratory biomarker analysis
Experimental: Arm B (cediranib maleate, lenalidomide)
Patients receive cediranib maleate PO QD on days 1-28 and lenalidomide PO QD on days 1-21 or 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Drug: cediranib maleate
Other Names:Drug: lenalidomide
Other Names:Other: laboratory biomarker analysis
I. Determine the maximum tolerated dose (MTD) of cediranib 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)
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: Patients receive cediranib maleate orally (PO) once daily (QD) on days 1-28 and lenalidomide PO QD on days 1-21 or 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Phase II: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive cediranib maleate PO QD on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive cediranib maleate PO and lenalidomide PO as in phase I.
After completion of study treatment, patients are followed up periodically.
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center||Recruiting|
|Chicago, Illinois, United States, 60637-1470|
|Contact: Jonas De Souza 317-948-7576 firstname.lastname@example.org|
|Principal Investigator: Jonas De Souza|
|Chicago, Illinois, United States, 60611|
|Contact: Mark Agulnik 312-695-1222 email@example.com|
|Principal Investigator: Mark Agulnik|
|Decatur Memorial Hospital||Recruiting|
|Decatur, Illinois, United States, 62526|
|Contact: James L. Wade 217-876-6600 JLWADE3@sbcgloab.net|
|Principal Investigator: James L. Wade|
|Ingalls Memorial Hospital||Recruiting|
|Harvey, Illinois, United States, 60426|
|Contact: Mark F. Kozloff 708-339-4800 firstname.lastname@example.org|
|Principal Investigator: Mark F. Kozloff|
|Peoria, Illinois, United States, 61615|
|Contact: Sachdev P. Thomas 309-243-1000 email@example.com|
|Principal Investigator: Sachdev P. Thomas|
|Central Illinois Hematology Oncology Center||Recruiting|
|Springfield, Illinois, United States, 60702|
|Contact: Edem S. Agamah 217-525-2500 firstname.lastname@example.org|
|Principal Investigator: Edem S. Agamah|
|United States, Indiana|
|Fort Wayne Medical Oncology and Hematology Inc - State Boulevard||Recruiting|
|Fort Wayne, Indiana, United States, 46845|
|Contact: Sreenivasa R. Nattam 260-484-8830 email@example.com|
|Principal Investigator: Sreenivasa R. Nattam|
|Indiana University Medical Center||Recruiting|
|Indianapolis, Indiana, United States, 46202|
|Contact: Romnee S. Clark 317-948-7576 firstname.lastname@example.org|
|Principal Investigator: Romnee S. Clark|
|United States, Maryland|
|University of Maryland Greenebaum Cancer Center||Recruiting|
|Baltimore, Maryland, United States, 21201-1595|
|Contact: Martin J. Edelman 410-328-2703 email@example.com|
|Principal Investigator: Martin J. Edelman|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center||Recruiting|
|Ann Arbor, Michigan, United States, 48109-0944|
|Contact: Francis P. Worden 734-936-0453 firstname.lastname@example.org|
|Principal Investigator: Francis P. Worden|
|United States, New Jersey|
|Cancer Institute of New Jersey||Recruiting|
|New Brunswick, New Jersey, United States, 08903|
|Contact: Joseph Aisner 732-235-7464 email@example.com|
|Principal Investigator: Joseph Aisner|
|United States, Tennessee|
|Vanderbilt University||Not yet recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: Jill Gilbert 615-343-4677 firstname.lastname@example.org|
|Principal Investigator: Jill Gilbert|
|United States, Virginia|
|Virginia Commonwealth University||Not yet recruiting|
|Richmond, Virginia, United States, 23298|
|Contact: John D. Roberts 804-628-1940 email@example.com|
|Principal Investigator: John D. Roberts|
|London Regional Cancer Program||Recruiting|
|London, Ontario, Canada, N6A 4L6|
|Contact: Eric W. Winquist 519-685-8500ext58640|
|Principal Investigator: Eric W. Winquist|
|University Health Network-Princess Margaret Hospital||Recruiting|
|Toronto, Ontario, Canada, M5G 2M9|
|Contact: Amit M. Oza 416-946-2818|
|Principal Investigator: Amit M. Oza|
|Principal Investigator:||Jonas De Souza||University of Chicago Comprehensive Cancer Center|