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

NCT01208051 | Completed Phase 1 Results DMC FDA Drug

• 15 other identifiers: NCI-2011-0253010-182-BCDR000068523610-182P8317_A23PAMDREVW02UCCRC-10-182-B8317N01CM00032N01CM00038N01CM00071N01CM00099N01CM00100N01CM62201P30CA014599U10CA180821
• Study Type: interventional
• Target: 127
• Locations: 2 countries
• Sites: 33

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Dose Limiting Toxicity

  Dose limiting toxicity was defined as any of the following occurring during the first cycle (28 days) of therapy: Hematological toxicities: * Any grade 4 neutropenia (ANC \< 500) lasting more than 5 days * Any grade 4 neutropenia with concomitant fever (temperature \> 38.5) * Any grade 4 neutropenia and sepsis or other severe infection * Any grade 4 thrombocytopenia Any other grade 3-4 non-hematological adverse drug reactions, except untreated nausea/vomiting, or hypersensitivity reactions. Grade 4 hypertension Grade 4 proteinuria Delay in the administration of a subsequent dose of cediranib and lenalidomide exceeding 2 weeks, due to an adverse drug reaction

  28 days

• Progression-free Survival (Phase II Futility Analysis)

  Time from enrollment on study to disease progression or death from any cause. Surviving patients without progression are censored as of the date of the last negative examination. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. This analysis corresponds to the planned futility analysis after 40 events.

  Assessed up to 3 years

• Progression-free Survival (Final Results After Crossover)

  Time from study enrollment until disease progression or death from any cause. Surviving patients without progression are censored as of the date of the last negative examination. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  Assessed up to 3 years

Secondary Outcomes (5)

• Objective Response Rate

  Assessed up to 3 years

• Overall Survival (Final Results After Crossover)

  24 months

• Percent Change in Tumor Size (Phase II)

  From baseline to 2 months

• Serial Measurements of Thyroid Stimulating Hormone and Thyroglobulin

  Up to 3 years

• Presence or Absence of B-RAF and RAS Mutations and Outcomes

  Up to 3 years

Study Arms (2)

Arm A (cediranib maleate)

EXPERIMENTAL

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.

Drug: Cediranib; Drug: Cediranib Maleate; Other: Laboratory Biomarker Analysis

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

EXPERIMENTAL

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.

Drug: Cediranib; Drug: Cediranib Maleate; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide

Interventions

Cediranib DRUG

Given PO

Also known as: AZD2171

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

Cediranib Maleate DRUG

Given PO

Also known as: AZD2171, AZD2171 Maleate, Recentin

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

Laboratory Biomarker Analysis OTHER

Correlative studies

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

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (33)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center P2C

Sacramento, California, 95817, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, 60451, United States

Location

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

Location

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, 46845, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Minnesota Oncology Hematology PA-Minneapolis

Minneapolis, Minnesota, 55407, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Penn State Children's Hospital

Hershey, Pennsylvania, 17033, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Adenocarcinoma, Follicular; Thyroid cancer, Hurthle cell; Thyroid Cancer, Papillary

Interventions

cediranib; Lenalidomide

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma, Papillary; Thyroid Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Chih-Yi Liao, MD
• Organization: University of Chicago

andyliao@medicine.bsd.uchicago.edu

(773) 702-6241

Study Officials

• Chih-Yi Liao

  University of Chicago Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Phase 1 was dose finding. Phase 2 parallel group comparison.

Study Record Dates

• First Submitted: September 22, 2010
• First Posted: September 23, 2010
• Study Start: September 9, 2010
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2020
• Last Updated: July 15, 2021
• Results First Posted: July 15, 2021

Record last verified: 2021-06

Locations

CA (3); US (30)