Cediranib Maleate With or Without Lenalidomide in Treating Patients With Thyroid Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01208051
First received: September 22, 2010
Last updated: September 16, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
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
Drug: lenalidomide
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • Objective response rate (Phase I) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: Up to 4 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 4 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 4 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.


Estimated Enrollment: 128
Study Start Date: September 2010
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Given PO
Other Names:
  • AZD2171
  • Recentin
Other: laboratory biomarker analysis
Correlative studies
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
Given PO
Other Names:
  • AZD2171
  • Recentin
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed papillary, follicular, papillary/follicular variant or Hürthle cell carcinoma; patients must be felt to be poor candidates for or refractory to further surgery or radioactive I-131 therapy; I-131 therapy must have been completed at least 4 weeks prior to enrollment; all patients are expected to be on thyroxine suppression therapy
  • Patients must have radiographically measurable disease; radiographically measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan; lesions in previously irradiated anatomic areas (external beam radiation) cannot be considered target lesions unless there has been documented growth of those lesions after radiotherapy
  • Patients must have evidence of disease progression (20% objective growth of existing tumors by Response Evaluation Criteria In Solid Tumors [RECIST] criteria) within the last 12 months
  • In the Phase I portion, there is no limit on prior systemic therapies (cytotoxic or targeted therapies); however, patients who have discontinued previous vascular endothelial growth factor (VEGF) inhibitors secondary to adverse events are not eligible; in the Phase 2 portion, patients cannot have received more than 1 prior chemotherapy (cytotoxic or targeted) regimen; prior VEGF-pathway inhibitors or B-RAF inhibitors are permissible
  • Life expectancy of greater than 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 (Karnofsky > 60%)
  • Leukocytes > 3,000/mcL
  • Absolute neutrophil count (ANC) > 1,500/mcL
  • Platelets > 100,000/mcL
  • Hemoglobin > 9 g/dL
  • Serum calcium < 12.0 mg/dL
  • Total serum bilirubin below or equal to upper limit of institutional normal

    • Patients with hyperbilirubinemia due to Gilbert's syndrome may enroll in the trial
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times upper limit of normal
  • Creatinine below or equal to upper limit of institutional normal OR creatinine clearance > 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Patients must have corrected QT interval (QTc) < 480 msec
  • The following groups of patients are eligible provided that they have New York Heart Association (NYHA) class II cardiac function on baseline echocardiogram (ECHO)/multi-gated acquisition scan (MUGA):

    • Those with a history of class II heart failure who are asymptomatic on treatment
    • Those with prior anthracycline exposure
    • Those who have received central thoracic radiotherapy that included the heart in the radiotherapy port
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure

    • A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Females of childbearing potential (FCBP) who receive cediranib alone must also have a negative initial and ongoing pregnancy tests as described above; FCBP who receive cediranib alone must also commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking cediranib; men on cediranib alone must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; all patients receiving cediranib alone must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; at least 4 weeks must have elapsed since any major surgery; patients with prior use of thalidomide or lenalidomide are excluded
  • Patients may not be receiving any other investigational agents
  • Patients with known brain metastases should be excluded; N.B: patients with brain metastases with stable neurologic status following local therapy (surgery or radiation) for at least 8 weeks from definitive therapy and without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events are eligible for participation
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cediranib maleate, lenalidomide, or other agents used in this study
  • Patients with poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher) are ineligible
  • Patients with proteinuria 1+ or greater on urinalysis should collect a 24 hour urine collection; patients with greater than 1.5 gram protein/24 hours are excluded
  • Because lenalidomide may increase the risk of deep vein thrombosis (DVT) or pulmonary embolism (PE), patients must stop Epogen at least 4 weeks prior to enrollment
  • Patients with any condition (e.g., gastrointestinal tract disease resulting in malabsorption, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to absorb cediranib tablets or lenalidomide capsules are excluded; however, for patients who are unable to swallow cediranib tablets, cediranib tablets may be administered as a dispersion in water (ie, either drinking water, sterile water [for injection] or purified water); cediranib can be administered via nasogastric tube or gastrostomy tube; for patients unable to swallow lenalidomide whole, lenalidomide can be administered via gastrostomy feeding tube
  • Patients with any of the following conditions are excluded:

    • Serious or non-healing wound, ulcer, or bone fracture
    • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
    • Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry
    • History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry
    • History of pulmonary embolism within the past 12 months
    • Class III or IV heart failure as defined by the NYHA functional classification system
  • Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infections or psychiatric illnesses/social situations that would limit compliance with study requirements are ineligible
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with cediranib with or without lenalidomide
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01208051

  Show 32 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Jonas De Souza University of Chicago
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01208051     History of Changes
Other Study ID Numbers: NCI-2011-02530, NCI-2011-02530, UCCRC-10-182-B, CDR0000685236, 10-182-B, 8317, N01CM00038, N01CM00071, P30CA014599, N01CM62201, N01CM00032
Study First Received: September 22, 2010
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Thyroid Neoplasms
Thyroid Diseases
Carcinoma
Adenocarcinoma, Follicular
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Lenalidomide
Thalidomide
Cediranib
Maleic acid
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014