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

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT01208051
Collaborator
(none)
127
Enrollment
33
Locations
2
Arms
112.8
Actual Duration (Months)
3.8
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. 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
    1. 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:
  1. 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
127 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Phase 1 was dose finding. Phase 2 parallel group comparison.Phase 1 was dose finding. Phase 2 parallel group comparison.
Masking:
None (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
Actual Study Start Date :
Sep 9, 2010
Actual Primary Completion Date :
Feb 1, 2020
Actual Study Completion Date :
Feb 1, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Cediranib
Given PO
Other Names:
  • AZD2171

    • Drug: Cediranib Maleate
    Given PO
    Other Names:
  • AZD2171
  • AZD2171 Maleate
  • Recentin

    • Other: Laboratory Biomarker Analysis
    Correlative studies
    Experimental: 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.

    Drug: Cediranib
    Given PO
    Other Names:
  • AZD2171

    • Drug: Cediranib Maleate
    Given PO
    Other Names:
  • AZD2171
  • AZD2171 Maleate
  • Recentin

    • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Lenalidomide
    Given PO
    Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Dose Limiting Toxicity [28 days]

      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

    2. Progression-free Survival (Phase II Futility Analysis) [Assessed up to 3 years]

      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.

    3. Progression-free Survival (Final Results After Crossover) [Assessed up to 3 years]

      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.

    Secondary Outcome Measures

    1. Objective Response Rate [Assessed up to 3 years]

      Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    2. Overall Survival (Final Results After Crossover) [24 months]

      Time from randomization to death from any cause. Patients who have not died are censored as of the date last known alive.

    3. Percent Change in Tumor Size (Phase II) [From baseline to 2 months]

      The percent change in tumor size from baseline to the end of cycle 2 (two months). The post-treatment total sum of lengths for a patient with a new lesion at cycle 2 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 Response Evaluation Criteria in Solid Tumors criteria. In the event of any early deaths prior to cycle 2, a nonparametric rank sum test will be used with deaths ranked at the extreme end of the distribution.

    4. Serial Measurements of Thyroid Stimulating Hormone and Thyroglobulin [Up to 3 years]

      Thyroid stimulating hormone and thyroglobulin levels

    5. Presence or Absence of B-RAF and RAS Mutations and Outcomes [Up to 3 years]

      Presence or absence of B-RAF and RAS mutations at baseline--to be correlated with response rates, progression-free survival, and overall survival.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    2 USC / Norris Comprehensive Cancer Center Los Angeles California United States 90033
    3 University of California Davis Comprehensive Cancer Center P2C Sacramento California United States 95817
    4 University of California Davis Comprehensive Cancer Center Sacramento California United States 95817
    5 City of Hope South Pasadena South Pasadena California United States 91030
    6 University of Colorado Hospital Aurora Colorado United States 80045
    7 Moffitt Cancer Center Tampa Florida United States 33612
    8 Northwestern University Chicago Illinois United States 60611
    9 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
    10 Decatur Memorial Hospital Decatur Illinois United States 62526
    11 NorthShore University HealthSystem-Evanston Hospital Evanston Illinois United States 60201
    12 Ingalls Memorial Hospital Harvey Illinois United States 60426
    13 UC Comprehensive Cancer Center at Silver Cross New Lenox Illinois United States 60451
    14 Illinois CancerCare-Peoria Peoria Illinois United States 61615
    15 Fort Wayne Medical Oncology and Hematology Inc-Parkview Fort Wayne Indiana United States 46845
    16 Indiana University/Melvin and Bren Simon Cancer Center Indianapolis Indiana United States 46202
    17 University of Maryland/Greenebaum Cancer Center Baltimore Maryland United States 21201
    18 University of Michigan Comprehensive Cancer Center Ann Arbor Michigan United States 48109
    19 Wayne State University/Karmanos Cancer Institute Detroit Michigan United States 48201
    20 Minnesota Oncology Hematology PA-Minneapolis Minneapolis Minnesota United States 55407
    21 Metro Minnesota Community Oncology Research Consortium Saint Louis Park Minnesota United States 55416
    22 Washington University School of Medicine Saint Louis Missouri United States 63110
    23 Mercy Hospital Saint Louis Saint Louis Missouri United States 63141
    24 Rutgers Cancer Institute of New Jersey New Brunswick New Jersey United States 08903
    25 UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina United States 27599
    26 Penn State Children's Hospital Hershey Pennsylvania United States 17033
    27 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
    28 Vanderbilt University/Ingram Cancer Center Nashville Tennessee United States 37232
    29 M D Anderson Cancer Center Houston Texas United States 77030
    30 University of Wisconsin Hospital and Clinics Madison Wisconsin United States 53792
    31 Tom Baker Cancer Centre Calgary Alberta Canada T2N 4N2
    32 London Regional Cancer Program London Ontario Canada N6A 4L6
    33 University Health Network-Princess Margaret Hospital Toronto Ontario Canada M5G 2M9

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Chih-Yi Liao, University of Chicago Comprehensive Cancer Center

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01208051
    Other Study ID Numbers:
    • NCI-2011-02530
    • NCI-2011-02530
    • 10-182-B
    • CDR0000685236
    • 10-182
    • P8317_A23PAMDREVW02
    • UCCRC-10-182-B
    • 8317
    • 8317
    • N01CM00032
    • N01CM00038
    • N01CM00071
    • N01CM00099
    • N01CM00100
    • N01CM62201
    • P30CA014599
    • U10CA180821
    First Posted:
    Sep 23, 2010
    Last Update Posted:
    Jul 15, 2021
    Last Verified:
    Jun 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Carcinoma
    Thyroid Neoplasms
    Carcinoma, Papillary
    Thyroid Cancer, Papillary
    Adenocarcinoma, Follicular
    Thyroid Diseases
    Lenalidomide
    Cediranib
    Maleic acid

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Phase I Dose Level 0 Phase I Dose Level +1 Phase I Dose Level +2 Phase II Arm A (Cediranib Maleate) Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
    Arm/Group Description Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
    Period Title: Total Enrollment
    STARTED 4 7 6 39 71
    COMPLETED 4 6 5 39 69
    NOT COMPLETED 0 1 1 0 2
    Period Title: Total Enrollment
    STARTED 0 0 0 39 68
    COMPLETED 0 0 0 39 68
    NOT COMPLETED 0 0 0 0 0
    Period Title: Total Enrollment
    STARTED 0 0 0 39 69
    COMPLETED 0 0 0 39 69
    NOT COMPLETED 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Phase I Dose Level 0 Phase I Dose Level +1 Phase I Dose Level +2 Phase II Arm A (Cediranib Maleate) Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015) Total
    Arm/Group Description Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO Total of all reporting groups
    Overall Participants 4 6 5 39 69 123
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    72.2
    64.5
    67.2
    61.9
    63.8
    63.1
    Sex: Female, Male (Count of Participants)
    Female
    4
    100%
    4
    66.7%
    3
    60%
    24
    61.5%
    40
    58%
    75
    61%
    Male
    0
    0%
    2
    33.3%
    2
    40%
    15
    38.5%
    29
    42%
    48
    39%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    1
    2.6%
    0
    0%
    1
    0.8%
    Asian
    0
    0%
    0
    0%
    1
    20%
    3
    7.7%
    4
    5.8%
    8
    6.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    5
    12.8%
    2
    2.9%
    7
    5.7%
    White
    4
    100%
    6
    100%
    4
    80%
    30
    76.9%
    59
    85.5%
    103
    83.7%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.4%
    1
    0.8%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    4.3%
    3
    2.4%
    Region of Enrollment (participants) [Number]
    Canada
    0
    0%
    0
    0%
    0
    0%
    5
    12.8%
    7
    10.1%
    12
    9.8%
    United States
    4
    100%
    6
    100%
    5
    100%
    34
    87.2%
    62
    89.9%
    111
    90.2%

    Outcome Measures

    1. Primary Outcome
    Title Dose Limiting Toxicity
    Description 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
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    Dose limiting toxicity was no an endpoint for the phase II study.
    Arm/Group Title Phase I Dose Level 0 Phase I Dose Level +1 Phase I Dose Level +2 Phase II Arm A (Cediranib Maleate) Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
    Arm/Group Description Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
    Measure Participants 4 6 5 0 0
    Count of Participants [Participants]
    0
    0%
    1
    16.7%
    2
    40%
    2. Primary Outcome
    Title Progression-free Survival (Phase II Futility Analysis)
    Description 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.
    Time Frame Assessed up to 3 years

    Outcome Measure Data

    Analysis Population Description
    Phase I study did not have a futility analysis. For phase II, one patient in Arm B was enrolled while the futility analysis was ongoing.
    Arm/Group Title Phase I Dose Level 0 Phase I Dose Level +1 Phase I Dose Level +2 Phase II Arm A (Cediranib Maleate) Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
    Arm/Group Description Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
    Measure Participants 0 0 0 39 68
    Median (95% Confidence Interval) [months]
    20.9
    10.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Phase II Arm A (Cediranib Maleate), Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.26
    Comments p-value is stratified by randomization factors.
    Method Log Rank
    Comments The conditional power was 7.8%, reaching the futility boundary of <15%. Patients on the combination arm were then crossed over to cediranib alone.
    3. Primary Outcome
    Title Progression-free Survival (Final Results After Crossover)
    Description 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.
    Time Frame Assessed up to 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Level 0 Dose Level +1 Dose Level +2 Phase II Arm A (Cediranib Maleate) Phase II Arm B (Cediranib Maleate Plus Lenalidomide)
    Arm/Group Description Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
    Measure Participants 4 6 5 39 69
    Median (95% Confidence Interval) [months]
    NA
    14.8
    23.6
    14.8
    11.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Phase II Arm A (Cediranib Maleate), Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.36
    Comments
    Method Log Rank
    Comments
    4. Secondary Outcome
    Title Objective Response Rate
    Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
    Time Frame Assessed up to 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Level 0 Dose Level +1 Dose Level +2 Phase II Arm A (Cediranib Maleate) Phase II Arm B (Cediranib Maleate Plus Lenalidomide)
    Arm/Group Description Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
    Measure Participants 4 6 5 39 69
    Count of Participants [Participants]
    0
    0%
    2
    33.3%
    4
    80%
    17
    43.6%
    30
    43.5%
    5. Secondary Outcome
    Title Overall Survival (Final Results After Crossover)
    Description Time from randomization to death from any cause. Patients who have not died are censored as of the date last known alive.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Level 0 Dose Level +1 Dose Level +2 Phase II Arm A (Cediranib Maleate) Phase II Arm B (Cediranib Maleate Plus Lenalidomide)
    Arm/Group Description Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
    Measure Participants 4 6 5 39 69
    Number (95% Confidence Interval) [percentage of participants]
    NA
    NaN
    60.0
    1000%
    100
    2000%
    64.8
    166.2%
    75.3
    109.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Phase II Arm A (Cediranib Maleate), Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.80
    Comments
    Method Log Rank
    Comments
    6. Secondary Outcome
    Title Percent Change in Tumor Size (Phase II)
    Description The percent change in tumor size from baseline to the end of cycle 2 (two months). The post-treatment total sum of lengths for a patient with a new lesion at cycle 2 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 Response Evaluation Criteria in Solid Tumors criteria. In the event of any early deaths prior to cycle 2, a nonparametric rank sum test will be used with deaths ranked at the extreme end of the distribution.
    Time Frame From baseline to 2 months

    Outcome Measure Data

    Analysis Population Description
    Percent change in tumor size was not an endpoint for the phase I study.
    Arm/Group Title Phase I Dose Level 0 Dose Level +1 Dose Level +2 Phase II Arm A (Cediranib Maleate) Phase II Arm B (Cediranib Maleate Plus Lenalidomide)
    Arm/Group Description Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
    Measure Participants 0 0 0 38 63
    Median (Inter-Quartile Range) [percent change]
    -12.5
    -4.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Phase II Arm A (Cediranib Maleate), Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.83
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    7. Secondary Outcome
    Title Serial Measurements of Thyroid Stimulating Hormone and Thyroglobulin
    Description Thyroid stimulating hormone and thyroglobulin levels
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    These outcomes were not assessed in the Phase I study. These data were not collected and analyzed for the phase II study because combination treatment was stopped due to reaching futility criteria at interim analysis.
    Arm/Group Title Phase I Dose Level 0 Phase I Dose Level +1 Phase I Dose Level +2 Phase II Arm A (Cediranib Maleate) Phase II Arm B (Cediranib Maleate Plus Lenalidomide)
    Arm/Group Description Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
    Measure Participants 0 0 0 0 0
    8. Secondary Outcome
    Title Presence or Absence of B-RAF and RAS Mutations and Outcomes
    Description Presence or absence of B-RAF and RAS mutations at baseline--to be correlated with response rates, progression-free survival, and overall survival.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    Mutations were not endpoints for the phase I study. These data were not collected and analyzed in the phase II study because combination treatment was stopped due to reaching futility criteria at interim analysis.
    Arm/Group Title Dose Level 0 Dose Level +1 Dose Level +2 Phase II Arm A (Cediranib Maleate) Phase II Arm B (Cediranib Maleate Plus Lenalidomide)
    Arm/Group Description Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
    Measure Participants 0 0 0 0 0

    Adverse Events

    Time Frame Up to 3 years
    Adverse Event Reporting Description
    Arm/Group Title Phase I Dose Level 0 Phase I Dose Level +1 Phase I Dose Level +2 Phase II Arm A (Cediranib Maleate) Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
    Arm/Group Description Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle) Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies 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. Cediranib: Given PO Cediranib Maleate: Given PO Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
    All Cause Mortality
    Phase I Dose Level 0 Phase I Dose Level +1 Phase I Dose Level +2 Phase II Arm A (Cediranib Maleate) Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/6 (0%) 0/5 (0%) 8/39 (20.5%) 13/69 (18.8%)
    Serious Adverse Events
    Phase I Dose Level 0 Phase I Dose Level +1 Phase I Dose Level +2 Phase II Arm A (Cediranib Maleate) Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/4 (50%) 3/6 (50%) 5/5 (100%) 16/39 (41%) 32/69 (46.4%)
    Blood and lymphatic system disorders
    Anemia 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 2/69 (2.9%)
    Febrile neutropenia 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Cardiac disorders
    Chest pain - cardiac 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Ejection fraction decreased 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Sinus bradycardia 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 2/69 (2.9%)
    Endocrine disorders
    Endocrine disorders - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Hypothyroidism 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Eye disorders
    Eye disorders - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Gastrointestinal disorders
    Abdominal pain 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 1/69 (1.4%)
    Colitis 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Constipation 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Diarrhea 0/4 (0%) 0/6 (0%) 1/5 (20%) 2/39 (5.1%) 4/69 (5.8%)
    Duodenal ulcer 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Dysphagia, esophagitis, odynophagia 1/4 (25%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 1/69 (1.4%)
    Vomiting 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Mucositis oral 0/4 (0%) 0/6 (0%) 1/5 (20%) 0/39 (0%) 0/69 (0%)
    General disorders
    Death NOS 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 1/69 (1.4%)
    Fatigue 0/4 (0%) 0/6 (0%) 1/5 (20%) 0/39 (0%) 1/69 (1.4%)
    Flu like symptoms 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 0/69 (0%)
    General disorders and administration site conditions - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Pain 0/4 (0%) 1/6 (16.7%) 0/5 (0%) 1/39 (2.6%) 0/69 (0%)
    Sudden death NOS 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 0/69 (0%)
    Non-cardiac chest pain 0/4 (0%) 0/6 (0%) 1/5 (20%) 0/39 (0%) 0/69 (0%)
    Fever 0/4 (0%) 1/6 (16.7%) 0/5 (0%) 0/39 (0%) 0/69 (0%)
    Hepatobiliary disorders
    Gallbladder perforation 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Hepatobiliary disorders - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Infections and infestations
    Bronchial infection 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Lung infection 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 2/69 (2.9%)
    Prostate infection 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Skin infection 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Infections and infestations - Other 0/4 (0%) 1/6 (16.7%) 0/5 (0%) 0/39 (0%) 0/69 (0%)
    Kidney infection 0/4 (0%) 1/6 (16.7%) 0/5 (0%) 0/39 (0%) 0/69 (0%)
    Sepsis 0/4 (0%) 1/6 (16.7%) 0/5 (0%) 0/39 (0%) 0/69 (0%)
    Urinary tract infection 0/4 (0%) 1/6 (16.7%) 0/5 (0%) 0/39 (0%) 0/69 (0%)
    Injury, poisoning and procedural complications
    Fall 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Fracture 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Investigations
    Blood bilirubin increase 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 2/69 (2.9%)
    Creatinine increased 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 2/69 (2.9%)
    Neutrophil count decreased 0/4 (0%) 0/6 (0%) 1/5 (20%) 0/39 (0%) 2/69 (2.9%)
    Platelet count decreased 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 0/69 (0%)
    Weight loss 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 0/69 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 3/69 (4.3%)
    Hypercalcemia 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 2/69 (2.9%)
    Hypoalbuminemia 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Hypocalcemia 0/4 (0%) 1/6 (16.7%) 0/5 (0%) 0/39 (0%) 2/69 (2.9%)
    Hypokalemia 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 2/69 (2.9%)
    Hyponatremia 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 2/69 (2.9%)
    Anorexia 0/4 (0%) 0/6 (0%) 1/5 (20%) 0/39 (0%) 0/69 (0%)
    Musculoskeletal and connective tissue disorders
    Generalized muscle weakness 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 2/69 (2.9%)
    Pain in extremity 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 2/69 (2.9%)
    Soft tissue necrosis lower limb 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Bone pain 0/4 (0%) 1/6 (16.7%) 0/5 (0%) 0/39 (0%) 0/69 (0%)
    Muscle weakness lower limb 0/4 (0%) 1/6 (16.7%) 0/5 (0%) 0/39 (0%) 0/69 (0%)
    Back pain 0/4 (0%) 0/6 (0%) 1/5 (20%) 0/39 (0%) 0/69 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benihn, malignant and unspecified - Other 0/4 (0%) 0/6 (0%) 2/5 (40%) 0/39 (0%) 1/69 (1.4%)
    Nervous system disorders
    Cognitive disturbance 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Headache 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 1/69 (1.4%)
    Stroke 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 1/69 (1.4%)
    Syncope 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 1/69 (1.4%)
    Neuralgia 0/4 (0%) 1/6 (16.7%) 0/5 (0%) 0/39 (0%) 0/69 (0%)
    Seizure 0/4 (0%) 0/6 (0%) 1/5 (20%) 0/39 (0%) 0/69 (0%)
    Psychiatric disorders
    Confusion 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 2/69 (2.9%)
    Delirium 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Renal and urinary disorders
    Proteinuria 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 2/69 (2.9%)
    Respiratory, thoracic and mediastinal disorders
    Bronchopulmonary hemorrhage 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 2/69 (2.9%)
    Cough 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 0/69 (0%)
    Dyspnea 0/4 (0%) 1/6 (16.7%) 1/5 (20%) 0/39 (0%) 5/69 (7.2%)
    Pleural effusion 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 2/69 (2.9%)
    Pleuritic pain 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 0/69 (0%)
    Pneumonitis 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 0/69 (0%)
    Pneumothorax 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Hypoxia 0/4 (0%) 1/6 (16.7%) 0/5 (0%) 0/39 (0%) 0/69 (0%)
    Aspiration 0/4 (0%) 0/6 (0%) 1/5 (20%) 0/39 (0%) 0/69 (0%)
    Skin and subcutaneous tissue disorders
    Palmar-plantar erythrodysesthesia syndrome 1/4 (25%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 2/69 (2.9%)
    Rash maculo-papular 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Social circumstances
    Social circumstances - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 0/69 (0%)
    Surgical and medical procedures
    Surgical and medical procedures - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Vascular disorders
    Hematoma 0/4 (0%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 1/69 (1.4%)
    Thromboembolic event 1/4 (25%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 1/69 (1.4%)
    Other (Not Including Serious) Adverse Events
    Phase I Dose Level 0 Phase I Dose Level +1 Phase I Dose Level +2 Phase II Arm A (Cediranib Maleate) Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/4 (100%) 6/6 (100%) 5/5 (100%) 38/39 (97.4%) 66/69 (95.7%)
    Blood and lymphatic system disorders
    Anemia 1/4 (25%) 3/6 (50%) 2/5 (40%) 10/39 (25.6%) 18/69 (26.1%)
    Cardiac disorders
    Sinus tachycardia 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 0/69 (0%)
    Ear and labyrinth disorders
    Ear and labyrinth disorders - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 0/69 (0%)
    Ear pain 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 1/69 (1.4%)
    Endocrine disorders
    Hyperthyroidism 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 3/69 (4.3%)
    Hypothyroidism 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 2/69 (2.9%)
    Eye disorders
    Blurred visioin 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 4/69 (5.8%)
    Eye disorders - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 3/69 (4.3%)
    Gastrointestinal disorders
    Abdominal pain 1/4 (25%) 1/6 (16.7%) 0/5 (0%) 6/39 (15.4%) 10/69 (14.5%)
    Constipation 1/4 (25%) 1/6 (16.7%) 2/5 (40%) 12/39 (30.8%) 24/69 (34.8%)
    Diarrhea 4/4 (100%) 5/6 (83.3%) 5/5 (100%) 32/39 (82.1%) 57/69 (82.6%)
    Dry mouth 0/4 (0%) 0/6 (0%) 0/5 (0%) 9/39 (23.1%) 8/69 (11.6%)
    Dyspepsia 1/4 (25%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 4/69 (5.8%)
    Dysphagia 0/4 (0%) 0/6 (0%) 0/5 (0%) 3/39 (7.7%) 12/69 (17.4%)
    Gastroesophageal reflux disease 0/4 (0%) 0/6 (0%) 0/5 (0%) 3/39 (7.7%) 0/69 (0%)
    Gastrointestinal disorders - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 4/39 (10.3%) 6/69 (8.7%)
    Mucositis oral 4/4 (100%) 6/6 (100%) 4/5 (80%) 11/39 (28.2%) 28/69 (40.6%)
    Nausea 1/4 (25%) 1/6 (16.7%) 2/5 (40%) 17/39 (43.6%) 30/69 (43.5%)
    Oral dysesthesia 0/4 (0%) 0/6 (0%) 0/5 (0%) 4/39 (10.3%) 3/69 (4.3%)
    Oral pain 0/4 (0%) 0/6 (0%) 0/5 (0%) 3/39 (7.7%) 7/69 (10.1%)
    Vomiting 0/4 (0%) 1/6 (16.7%) 1/5 (20%) 14/39 (35.9%) 14/69 (20.3%)
    General disorders
    Edema limbs 0/4 (0%) 0/6 (0%) 0/5 (0%) 3/39 (7.7%) 10/69 (14.5%)
    Fatigue 4/4 (100%) 6/6 (100%) 5/5 (100%) 31/39 (79.5%) 57/69 (82.6%)
    Fever 0/4 (0%) 0/6 (0%) 0/5 (0%) 4/39 (10.3%) 2/69 (2.9%)
    General disorders and administration site conditions - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 4/69 (5.8%)
    Malaise 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 2/69 (2.9%)
    Non-cardiac chest pain 0/4 (0%) 1/6 (16.7%) 1/5 (20%) 4/39 (10.3%) 4/69 (5.8%)
    Pain 1/4 (25%) 1/6 (16.7%) 1/5 (20%) 11/39 (28.2%) 12/69 (17.4%)
    Flu like symptoms 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 1/69 (1.4%)
    Multi-organ failure 0/4 (0%) 1/6 (16.7%) 0/5 (0%) 0/39 (0%) 0/69 (0%)
    Salivary duct inflammation 0/4 (0%) 1/6 (16.7%) 0/5 (0%) 0/39 (0%) 0/69 (0%)
    Infections and infestations
    Infections and infestations - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 6/69 (8.7%)
    Urinary tract infection 0/4 (0%) 1/6 (16.7%) 0/5 (0%) 4/39 (10.3%) 2/69 (2.9%)
    Papulopustular rash 0/4 (0%) 0/6 (0%) 1/5 (20%) 0/39 (0%) 0/69 (0%)
    Injury, poisoning and procedural complications
    Fall 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 1/69 (1.4%)
    Investigations
    Alanine aminotransferase increased 2/4 (50%) 5/6 (83.3%) 3/5 (60%) 12/39 (30.8%) 31/69 (44.9%)
    Alkaline phosphatase increased 2/4 (50%) 2/6 (33.3%) 1/5 (20%) 6/39 (15.4%) 15/69 (21.7%)
    Aspartate aminotransferase increased 2/4 (50%) 5/6 (83.3%) 2/5 (40%) 12/39 (30.8%) 26/69 (37.7%)
    Blood bilirubin increased 1/4 (25%) 4/6 (66.7%) 0/5 (0%) 4/39 (10.3%) 9/69 (13%)
    Creatinine increase 0/4 (0%) 0/6 (0%) 1/5 (20%) 5/39 (12.8%) 15/69 (21.7%)
    Investigations - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 4/39 (10.3%) 3/69 (4.3%)
    Lymphocyte count decreased 2/4 (50%) 0/6 (0%) 3/5 (60%) 7/39 (17.9%) 12/69 (17.4%)
    Neutrophil count decreased 1/4 (25%) 1/6 (16.7%) 3/5 (60%) 3/39 (7.7%) 30/69 (43.5%)
    Platelet count decreased 2/4 (50%) 3/6 (50%) 3/5 (60%) 6/39 (15.4%) 25/69 (36.2%)
    Weight loss 0/4 (0%) 0/6 (0%) 1/5 (20%) 16/39 (41%) 20/69 (29%)
    White blood cell decreased 2/4 (50%) 2/6 (33.3%) 3/5 (60%) 3/39 (7.7%) 28/69 (40.6%)
    CD4 lymphocytes decreased 1/4 (25%) 1/6 (16.7%) 0/5 (0%) 0/39 (0%) 0/69 (0%)
    Lymphocyte count increased 1/4 (25%) 0/6 (0%) 1/5 (20%) 0/39 (0%) 0/69 (0%)
    Ejection fraction decreased 1/4 (25%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 0/69 (0%)
    Metabolism and nutrition disorders
    Anorexia 4/4 (100%) 4/6 (66.7%) 5/5 (100%) 22/39 (56.4%) 31/69 (44.9%)
    Dehydration 0/4 (0%) 0/6 (0%) 0/5 (0%) 5/39 (12.8%) 5/69 (7.2%)
    Glucose intolerance 0/4 (0%) 0/6 (0%) 0/5 (0%) 3/39 (7.7%) 2/69 (2.9%)
    Hypercalcemia 1/4 (25%) 0/6 (0%) 0/5 (0%) 3/39 (7.7%) 3/69 (4.3%)
    Hyperglycemia 1/4 (25%) 5/6 (83.3%) 4/5 (80%) 6/39 (15.4%) 13/69 (18.8%)
    Hyperkalemia 1/4 (25%) 0/6 (0%) 0/5 (0%) 6/39 (15.4%) 2/69 (2.9%)
    Hyperuricemia 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 0/69 (0%)
    Hypoalbuminemia 0/4 (0%) 1/6 (16.7%) 3/5 (60%) 8/39 (20.5%) 17/69 (24.6%)
    Hypocalcemia 3/4 (75%) 2/6 (33.3%) 2/5 (40%) 11/39 (28.2%) 17/69 (24.6%)
    Hypokalemia 1/4 (25%) 2/6 (33.3%) 3/5 (60%) 11/39 (28.2%) 20/69 (29%)
    Hypomagnesemia 0/4 (0%) 1/6 (16.7%) 1/5 (20%) 4/39 (10.3%) 6/69 (8.7%)
    Hyponatremia 0/4 (0%) 2/6 (33.3%) 1/5 (20%) 8/39 (20.5%) 13/69 (18.8%)
    Hypophosphatemia 0/4 (0%) 4/6 (66.7%) 0/5 (0%) 2/39 (5.1%) 9/69 (13%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/4 (0%) 1/6 (16.7%) 1/5 (20%) 6/39 (15.4%) 8/69 (11.6%)
    Back pain 0/4 (0%) 0/6 (0%) 0/5 (0%) 10/39 (25.6%) 8/69 (11.6%)
    Generalized muscle weakness 0/4 (0%) 0/6 (0%) 0/5 (0%) 5/39 (12.8%) 8/69 (11.6%)
    Musculoskeletal and connective tissue disorder - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 6/69 (8.7%)
    Myalgia 0/4 (0%) 2/6 (33.3%) 1/5 (20%) 6/39 (15.4%) 7/69 (10.1%)
    Neck pain 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 7/69 (10.1%)
    Pain in extremity 0/4 (0%) 1/6 (16.7%) 1/5 (20%) 5/39 (12.8%) 7/69 (10.1%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified - Other 0/4 (0%) 0/6 (0%) 1/5 (20%) 0/39 (0%) 0/69 (0%)
    Nervous system disorders
    Dizziness 0/4 (0%) 0/6 (0%) 0/5 (0%) 6/39 (15.4%) 10/69 (14.5%)
    Dysgeusia 0/4 (0%) 0/6 (0%) 1/5 (20%) 8/39 (20.5%) 17/69 (24.6%)
    Headache 0/4 (0%) 0/6 (0%) 1/5 (20%) 11/39 (28.2%) 20/69 (29%)
    Nervous system disorders - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 4/39 (10.3%) 1/69 (1.4%)
    Neuropathy-sensory 0/4 (0%) 0/6 (0%) 0/5 (0%) 4/39 (10.3%) 6/69 (8.7%)
    Paresthesia 0/4 (0%) 0/6 (0%) 0/5 (0%) 5/39 (12.8%) 1/69 (1.4%)
    Syncope 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 2/69 (2.9%)
    Tremor 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 2/69 (2.9%)
    Transient ischemic attacks 1/4 (25%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 0/69 (0%)
    Psychiatric disorders
    Anxiety 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 7/69 (10.1%)
    Confusion 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 2/69 (2.9%)
    Insomnia 0/4 (0%) 0/6 (0%) 0/5 (0%) 4/39 (10.3%) 6/69 (8.7%)
    Mood alteration-depression 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 2/69 (2.9%)
    Renal and urinary disorders
    Chronic kidney disease 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 2/69 (2.9%)
    Hematuria 0/4 (0%) 3/6 (50%) 2/5 (40%) 5/39 (12.8%) 3/69 (4.3%)
    Proteinuria 2/4 (50%) 5/6 (83.3%) 2/5 (40%) 18/39 (46.2%) 24/69 (34.8%)
    Renal and urinary disorders - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 2/69 (2.9%)
    Renal calculi 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 0/69 (0%)
    Reproductive system and breast disorders
    Vaginal hemorrhage 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 1/69 (1.4%)
    Respiratory, thoracic and mediastinal disorders
    Cough 0/4 (0%) 0/6 (0%) 0/5 (0%) 8/39 (20.5%) 16/69 (23.2%)
    Dyspnea 2/4 (50%) 0/6 (0%) 0/5 (0%) 6/39 (15.4%) 18/69 (26.1%)
    Hoarseness 0/4 (0%) 0/6 (0%) 1/5 (20%) 8/39 (20.5%) 11/69 (15.9%)
    Nasal congestion 0/4 (0%) 0/6 (0%) 0/5 (0%) 3/39 (7.7%) 4/69 (5.8%)
    Sore throat 0/4 (0%) 0/6 (0%) 0/5 (0%) 8/39 (20.5%) 3/69 (4.3%)
    Voice alteration 0/4 (0%) 0/6 (0%) 0/5 (0%) 2/39 (5.1%) 1/69 (1.4%)
    Skin and subcutaneous tissue disorders
    Alopecia 1/4 (25%) 1/6 (16.7%) 0/5 (0%) 3/39 (7.7%) 6/69 (8.7%)
    Dry skin 0/4 (0%) 0/6 (0%) 1/5 (20%) 1/39 (2.6%) 5/69 (7.2%)
    Palmar-plantar erythrodysesthesia syndrome 0/4 (0%) 1/6 (16.7%) 3/5 (60%) 15/39 (38.5%) 17/69 (24.6%)
    Pruritus 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 4/69 (5.8%)
    Rash maculo-papular 0/4 (0%) 0/6 (0%) 2/5 (40%) 3/39 (7.7%) 11/69 (15.9%)
    Rash acneiform 0/4 (0%) 0/6 (0%) 0/5 (0%) 1/39 (2.6%) 7/69 (10.1%)
    Skin and subcutaneous tissue disorders - Other 0/4 (0%) 0/6 (0%) 0/5 (0%) 6/39 (15.4%) 8/69 (11.6%)
    Vascular disorders
    Hypertension 1/4 (25%) 3/6 (50%) 0/5 (0%) 27/39 (69.2%) 44/69 (63.8%)
    Thromboembolic event 1/4 (25%) 0/6 (0%) 0/5 (0%) 0/39 (0%) 4/69 (5.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chih-Yi Liao, MD
    Organization University of Chicago
    Phone (773) 702-6241
    Email andyliao@medicine.bsd.uchicago.edu
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01208051
    Other Study ID Numbers:
    • NCI-2011-02530
    • NCI-2011-02530
    • 10-182-B
    • CDR0000685236
    • 10-182
    • P8317_A23PAMDREVW02
    • UCCRC-10-182-B
    • 8317
    • 8317
    • N01CM00032
    • N01CM00038
    • N01CM00071
    • N01CM00099
    • N01CM00100
    • N01CM62201
    • P30CA014599
    • U10CA180821
    First Posted:
    Sep 23, 2010
    Last Update Posted:
    Jul 15, 2021
    Last Verified:
    Jun 1, 2021