Cediranib Maleate With or Without Lenalidomide for the Treatment of Thyroid Cancer

NCT ID: NCT01208051

Last Updated: 2021-07-15

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

127 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-09-09

Study Completion Date

2020-02-01

Brief Summary

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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 Description

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PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of cediranib maleate (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)

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. Cycles 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. Cycles 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. NOTE: As of April 10, 2015, patients assigned to this arm are to discontinue lenalidomide and may continue on cediranib alone.

After completion of study treatment, patients are followed up periodically.

Conditions

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Refractory Differentiated Thyroid Gland Carcinoma Refractory Thyroid Gland Follicular Carcinoma Refractory Thyroid Gland Hurthle Cell Carcinoma Refractory Thyroid Gland Papillary Carcinoma Unresectable Thyroid Gland Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Phase 1 was dose finding. Phase 2 parallel group comparison.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A (cediranib maleate)

Patients receive cediranib maleate 30 mg PO QD on days 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Cediranib

Intervention Type DRUG

Given PO

Cediranib Maleate

Intervention Type DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Arm B (cediranib maleate plus lenalidomide thru April 10, 2015)

Patients receive cediranib maleate 30 mg PO and lenalidomide 15 mg PO on days 1-21. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: As of April 10, 2015, patients assigned to this arm are discontinued lenalidomide and continued on cediranib alone.

Group Type EXPERIMENTAL

Cediranib

Intervention Type DRUG

Given PO

Cediranib Maleate

Intervention Type DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Lenalidomide

Intervention Type DRUG

Given PO

Interventions

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Cediranib

Given PO

Intervention Type DRUG

Cediranib Maleate

Given PO

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Lenalidomide

Given PO

Intervention Type DRUG

Other Intervention Names

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AZD2171 AZD2171 AZD2171 Maleate Recentin CC-5013 CC5013 CDC 501 Revlimid

Eligibility Criteria

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Inclusion Criteria

* Patients must have histologically or cytologically confirmed papillary, follicular, papillary/follicular variant or Hurthle 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 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 x institutional upper limit of normal
* Creatinine below or equal to upper limit of institutional limits 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 radiation 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 because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; Note well (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, 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 1+ or greater proteinuria 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 (epoetin alfa) 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 of treatment
* 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 because cediranib and lenalidomide are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cediranib or lenalidomide, 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 because of the potential for pharmacokinetic interactions with cediranib or cediranib with lenalidomide; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Chih-Yi Liao

Role: PRINCIPAL_INVESTIGATOR

University of Chicago Comprehensive Cancer Center

Locations

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City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

University of California Davis Comprehensive Cancer Center P2C

Sacramento, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

City of Hope South Pasadena

South Pasadena, California, United States

Site Status

University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Decatur Memorial Hospital

Decatur, Illinois, United States

Site Status

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States

Site Status

Ingalls Memorial Hospital

Harvey, Illinois, United States

Site Status

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, United States

Site Status

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Site Status

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, United States

Site Status

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Minnesota Oncology Hematology PA-Minneapolis

Minneapolis, Minnesota, United States

Site Status

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Site Status

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Penn State Children's Hospital

Hershey, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Site Status

London Regional Cancer Program

London, Ontario, Canada

Site Status

University Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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NCI-2011-02530

Identifier Type: REGISTRY

Identifier Source: secondary_id

10-182-B

Identifier Type: -

Identifier Source: secondary_id

CDR0000685236

Identifier Type: -

Identifier Source: secondary_id

10-182

Identifier Type: -

Identifier Source: secondary_id

P8317_A23PAMDREVW02

Identifier Type: -

Identifier Source: secondary_id

UCCRC-10-182-B

Identifier Type: -

Identifier Source: secondary_id

8317

Identifier Type: OTHER

Identifier Source: secondary_id

8317

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM00032

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00038

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00071

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00099

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00100

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62201

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA014599

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02530

Identifier Type: -

Identifier Source: org_study_id

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