Cediranib Maleate in Treating Patients With Recurrent or Persistent Endometrial Cancer

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT01132820
Collaborator
NRG Oncology (Other)
53
87
1
67
0.6
0

Study Details

Study Description

Brief Summary

This phase II trial studies the side effects and how well cediranib maleate works in treating patients with endometrial cancer that has failed to respond to initial chemotherapy or has come back after surgery, radiation therapy, or other forms of treatment. Cediranib maleate may stop the growth of tumor cells by blocking proteins made by tumors that can stimulate growth of tumor cells as well as blood vessels in and around tumors.

Condition or Disease Intervention/Treatment Phase
  • Drug: Cediranib Maleate
  • Other: Laboratory Biomarker Analysis
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To assess the activity of cediranib (cediranib maleate) in patients with either persistent or recurrent endometrial carcinoma.

  2. To determine the frequency and degree of toxicity of cediranib as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version (v.)4.0 in this cohort of patients.

SECONDARY OBJECTIVES:
  1. To determine the duration of progression-free survival and overall survival. II. To estimate the probability of response without restriction on the duration of response documentation since study enrollment.
TERTIARY OBJECTIVES:
  1. To determine if the response to cediranib correlates with high-expression of its receptor targets (e.g., vascular endothelial growth factor receptor [VEGFR] [1, 2, 3] and platelet derived growth factor receptor [PDGFR]).

  2. To determine if the response to cediranib correlates with high endogenous circulating plasma levels of VEGFA, low-levels of its endogenous inhibitor, soluble fms-related tyrosine kinase 3 (sFlt-1) (the truncated, circulating portion of VEGFR-1), or circulating tissue factor (TF) or circulating prostate apoptosis response-4 (Par-4), both potential markers of tumor progression.

  3. To determine if a high-expression of VEGFA on pre-treatment tumor specimens correlates with response to cediranib.

  4. To determine if expression of phosphorylated mitogen activated protein kinase (ERK) 1 and 2, c-Jun, signal transducer and activator of transcription 3 (Stat3), protein kinase C (PKC), and phosphorylated ribosomal protein S6 (p70S6) kinase correlates with resistance or sensitivity to cediranib.

OUTLINE:

Patients receive cediranib maleate orally (PO) daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
53 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Evaluation of Cediranib (Recentin; AZD2171, IND#72740, NSC# 732208) in the Treatment of Recurrent or Persistent Endometrial Carcinoma
Study Start Date :
Jun 1, 2010
Actual Primary Completion Date :
Jan 1, 2016
Actual Study Completion Date :
Jan 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (cediranib maleate)

Patients receive cediranib maleate PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cediranib Maleate
Given PO
Other Names:
  • AZD2171
  • AZD2171 Maleate
  • Recentin
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of Adverse Effects as Assessed by the National Cancer Institute CTCAE v. 4.0 [Up to 5 years]

      Adverse Events (Grade 3 or higher)

    2. Tumor Response [For diesease evaluated by physical examination, response was assessed prior to each cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle from enrollment until stopping study therapy. The average time on study is 3 mnths]

      Complete and Partial Tumor Response by RECIST 1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by 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.

    3. Progression-free Survival (PFS) = > 6 Months [For disease evaluated by physical examination, progression was assessed prior to each cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle. Evaluated from time of enrollment until progression or death, up to 5 years]

      Number of participants who survived for at least 6 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v.1.0) 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. Overall Survival [From study entry to death or last contact, up to 5 years.]

      The observed length of life from entry into the study to death or the date of last contact.

    2. Progression Free Survival [Disease that can be assessed by physical exam should be evaluated every cycle. disease assessed by imaging should be evaluated every other cycle. Time frame to determine the date of progression is from the date of enrollment up to 5 years after enrollment]

      Time until disease progression, death, or date of last contact.

    3. Response Without Regard to the Time of Documented Response [Tumor responses with time restriction starts at enrollment and goes to 6 months after enrollment or until pt. off study therapy,whichever occurs first. Without time restriction starts at enrollment,lasts until off study therapy, median duration = 2.63 mth]

      Complete and partial tumor response by RECIST 1.1

    Other Outcome Measures

    1. Expression of Phosphorylated ERK1 and 2, c-Jun, Stat3, PKC, and p70S6 Kinase [Baseline]

    2. Levels of Receptor Targets Such as VEGFR (1, 2, 3) and PDGFR [Baseline]

    3. Plasma Levels of Endogenous Circulating VEGFA, Levels of Its Endogenous Inhibitor, sFlt-1 (the Truncated, Circulating Portion of VEGFR-1), Circulating TF, and Circulating Par-4 [Up to 5 years]

    4. VEGFA Expression on Pre-treatment Tumor Specimens [Baseline]

      High vs low expression.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients must have recurrent or persistent endometrial carcinoma, which is refractory to curative therapy or established treatments; histologic confirmation of the original primary tumor is required

    • Patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma

    • All patients must have measurable disease; measurable disease is defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1); measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI

    • Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST version 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

    • Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population

    • Patients who have received one prior regimen must have a GOG performance status of 0, 1, or 2; patients who have received two prior regimens must have a GOG performance status of 0 or 1

    • Recovery from effects of recent surgery, radiotherapy, or chemotherapy

    • Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])

    • Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration

    • Any other prior therapy directed at the malignant tumor must be discontinued at least three weeks prior to registration

    • Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen

    • Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease according to the following definition: cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa

    • Note: Patients on this non-cytotoxic study are allowed to receive one additional cytotoxic chemotherapy regimen for management of recurrent or persistent disease, as defined above; however, due to the novel nature of biologic compounds, patients are encouraged to enroll on second-line non-cytotoxic studies prior to receiving additional cytotoxic therapy

    • Patients must have NOT received any non-cytotoxic chemotherapy for management of recurrent or persistent disease; prior hormonal therapy is allowed

    • Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl

    • Platelets greater than or equal to 100,000/mcl

    • Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN) or creatinine (Cr) clearance >= 60 ml/min

    • Bilirubin less than or equal to 1.5 x upper limit of normal (ULN)

    • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) less than or equal to 2.5 x ULN

    • Alkaline phosphatase less than or equal to 2.5 x ULN

    • Neuropathy (sensory and motor) less than or equal to grade 1

    • Urine protein creatinine (UPC) ratio must be < 1.0 gm

    • If UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended

    • Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) =< 1.5 x ULN

    • Patients must have an amylase and lipase =< ULN

    • Patients must have a thyroid stimulating hormone (TSH) level and a free thyroxine (free T4) level within the institutional normal limits

    • Patients must have signed an approved informed consent and authorization permitting release of personal health information

    • Patients must meet pre-entry requirements as specified

    • Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing an effective form of contraception

    Exclusion Criteria:
    • Patients who have had prior therapy with cediranib (AZD 2171) or other VEGF pathway-targeted therapy

    • Patient with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies as noted, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy

    • Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease

    • Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease

    • Patients with serious, non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to the first date of cediranib (AZD 2171) therapy

    • Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels

    • Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy or any brain metastases

    • Patients with clinically significant cardiovascular disease; this includes:

    • Uncontrolled hypertension defined as systolic > 150 mmHg or diastolic > 100 mmHg despite optimized antihypertensive therapy

    • Myocardial infarction or unstable angina within 6 months of the first date of cediranib (AZD 2171) therapy

    • New York Heart Association (NYHA) grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication; women who have received prior treatment with an anthracycline (including doxorubicin and/or liposomal doxorubicin) and have an ejection fraction < institutional lower limit of normal (LLN) will be excluded from the study

    • CTCAE grade 2 or greater peripheral vascular disease

    • History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of cediranib (AZD 2171) therapy

    • Mean corrected QT interval (QTc) > 500 msec or history of familial long QT syndrome

    • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies

    • Patients undergoing invasive procedures as defined below:

    • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of cediranib (AZD 2171) therapy

    • Major surgical procedure anticipated during the course of the study

    • Minor surgical procedures, fine needle aspirates, or core biopsies within 7 days prior to the first date of cediranib (AZD2171) therapy

    • Patients who are pregnant or nursing

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Providence Saint Joseph Medical Center/Disney Family Cancer Center Burbank California United States 91505
    2 Palo Alto Medical Foundation-Gynecologic Oncology Mountain View California United States 94040
    3 Hartford Hospital Hartford Connecticut United States 06102
    4 The Hospital of Central Connecticut New Britain Connecticut United States 06050
    5 Sarasota Memorial Hospital Sarasota Florida United States 34239
    6 Central Georgia Gynecologic Oncology Macon Georgia United States 31201
    7 Rush University Medical Center Chicago Illinois United States 60612
    8 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
    9 Sudarshan K Sharma MD Limted-Gynecologic Oncology Hinsdale Illinois United States 60521
    10 Saint Vincent Oncology Center Indianapolis Indiana United States 46260
    11 Medical Oncology and Hematology Associates-West Des Moines Clive Iowa United States 50325
    12 Mercy Cancer Center-West Lakes Clive Iowa United States 50325
    13 Iowa Methodist Medical Center Des Moines Iowa United States 50309
    14 Iowa-Wide Oncology Research Coalition NCORP Des Moines Iowa United States 50309
    15 Medical Oncology and Hematology Associates-Des Moines Des Moines Iowa United States 50309
    16 Medical Oncology and Hematology Associates-Laurel Des Moines Iowa United States 50314
    17 Mercy Medical Center - Des Moines Des Moines Iowa United States 50314
    18 Iowa Lutheran Hospital Des Moines Iowa United States 50316
    19 University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa United States 52242
    20 Methodist West Hospital West Des Moines Iowa United States 50266-7700
    21 Mercy Medical Center-West Lakes West Des Moines Iowa United States 50266
    22 Cancer Center of Kansas - Chanute Chanute Kansas United States 66720
    23 Cancer Center of Kansas - Dodge City Dodge City Kansas United States 67801
    24 Cancer Center of Kansas - El Dorado El Dorado Kansas United States 67042
    25 Cancer Center of Kansas - Fort Scott Fort Scott Kansas United States 66701
    26 Cancer Center of Kansas-Independence Independence Kansas United States 67301
    27 Cancer Center of Kansas-Kingman Kingman Kansas United States 67068
    28 Lawrence Memorial Hospital Lawrence Kansas United States 66044
    29 Cancer Center of Kansas-Liberal Liberal Kansas United States 67901
    30 Cancer Center of Kansas - Newton Newton Kansas United States 67114
    31 Cancer Center of Kansas - Parsons Parsons Kansas United States 67357
    32 Cancer Center of Kansas - Pratt Pratt Kansas United States 67124
    33 Cancer Center of Kansas - Salina Salina Kansas United States 67401
    34 Cancer Center of Kansas - Wellington Wellington Kansas United States 67152
    35 Associates In Womens Health Wichita Kansas United States 67208
    36 Cancer Center of Kansas-Wichita Medical Arts Tower Wichita Kansas United States 67208
    37 Cancer Center of Kansas - Main Office Wichita Kansas United States 67214
    38 Via Christi Regional Medical Center Wichita Kansas United States 67214
    39 Wichita NCI Community Oncology Research Program Wichita Kansas United States 67214
    40 Cancer Center of Kansas - Winfield Winfield Kansas United States 67156
    41 Maine Medical Center-Bramhall Campus Portland Maine United States 04102
    42 Greater Baltimore Medical Center Baltimore Maryland United States 21204
    43 MedStar Franklin Square Medical Center/Weinberg Cancer Institute Baltimore Maryland United States 21237
    44 Borgess Medical Center Kalamazoo Michigan United States 49001
    45 Bronson Methodist Hospital Kalamazoo Michigan United States 49007
    46 West Michigan Cancer Center Kalamazoo Michigan United States 49007
    47 University of Mississippi Medical Center Jackson Mississippi United States 39216
    48 University of Missouri - Ellis Fischel Columbia Missouri United States 65212
    49 Cancer Research for the Ozarks NCORP Springfield Missouri United States 65804
    50 Mercy Hospital Springfield Springfield Missouri United States 65804
    51 CoxHealth South Hospital Springfield Missouri United States 65807
    52 Nebraska Methodist Hospital Omaha Nebraska United States 68114
    53 Women's Cancer Center of Nevada Las Vegas Nevada United States 89169
    54 Cooper Hospital University Medical Center Camden New Jersey United States 08103
    55 Saint Luke's Hospital-Warren Campus Phillipsburg New Jersey United States 08865
    56 Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina United States 28203
    57 Duke University Medical Center Durham North Carolina United States 27710
    58 University of Cincinnati Cincinnati Ohio United States 45267
    59 Case Western Reserve University Cleveland Ohio United States 44106
    60 Riverside Methodist Hospital Columbus Ohio United States 43214
    61 Kettering Medical Center Kettering Ohio United States 45429
    62 Lake University Ireland Cancer Center Mentor Ohio United States 44060
    63 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    64 Oklahoma Cancer Specialists and Research Institute-Tulsa Tulsa Oklahoma United States 74146
    65 Abington Memorial Hospital Abington Pennsylvania United States 19001
    66 Women and Infants Hospital Providence Rhode Island United States 02905
    67 Virginia Commonwealth University/Massey Cancer Center Richmond Virginia United States 23298
    68 PeaceHealth Medical Group PC Bellingham Washington United States 98226
    69 Harrison HealthPartners Hematology and Oncology-Bremerton Bremerton Washington United States 98310
    70 Harrison Medical Center Bremerton Washington United States 98310
    71 Providence Regional Cancer Partnership Everett Washington United States 98201
    72 Skagit Valley Hospital Regional Cancer Care Center Mount Vernon Washington United States 98273
    73 Harrison HealthPartners Hematology and Oncology-Poulsbo Poulsbo Washington United States 98370
    74 Pacific Gynecology Specialists Seattle Washington United States 98104
    75 Fred Hutchinson Cancer Research Center Seattle Washington United States 98109
    76 Seattle Cancer Care Alliance Seattle Washington United States 98109
    77 Group Health Cooperative-Seattle Seattle Washington United States 98112
    78 Swedish Medical Center-First Hill Seattle Washington United States 98122-4307
    79 Northwest Hospital Seattle Washington United States 98133
    80 University of Washington Medical Center Seattle Washington United States 98195
    81 Olympic Medical Cancer Care Center Sequim Washington United States 98384
    82 Cancer Care Northwest - Spokane South Spokane Washington United States 99202
    83 Rockwood Cancer Treatment Center-DHEC-Downtown Spokane Washington United States 99204
    84 MultiCare Tacoma General Hospital Tacoma Washington United States 98405
    85 Saint Joseph Medical Center Tacoma Washington United States 98405
    86 Providence Saint Mary Regional Cancer Center Walla Walla Washington United States 99362
    87 Wenatchee Valley Hospital and Clinics Wenatchee Washington United States 98801

    Sponsors and Collaborators

    • National Cancer Institute (NCI)
    • NRG Oncology

    Investigators

    • Principal Investigator: David Bender, NRG Oncology

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01132820
    Other Study ID Numbers:
    • NCI-2011-02043
    • NCI-2011-02043
    • GOG-0229J
    • CDR0000674008
    • GOG-0229J
    • GOG-0229J
    • U10CA180868
    • U10CA027469
    First Posted:
    May 28, 2010
    Last Update Posted:
    Aug 8, 2019
    Last Verified:
    Aug 1, 2019

    Study Results

    Participant Flow

    Recruitment Details The study was activated on 6/7/2010 and suspended to accrual on 3/7/2011. The study reopened on 11/21/2011 and closed on 4/30/2012.
    Pre-assignment Detail
    Arm/Group Title Cediranib
    Arm/Group Description Cediranib (RECENTIN; AZD2171) will be administered PO 30 mg daily. Each 28 day period will be considered a cycle. Treatment will continue until disease progression or adverse effects prohibit further therapy.
    Period Title: Overall Study
    STARTED 53
    COMPLETED 48
    NOT COMPLETED 5

    Baseline Characteristics

    Arm/Group Title Cediranib
    Arm/Group Description Cediranib (RECENTIN; AZD2171) will be administered PO 30 mg daily. Each 28 day period will be considered a cycle. Treatment will continue until disease progression or adverse effects prohibit further therapy.
    Overall Participants 48
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    64.9
    (9.5)
    Age, Customized (Count of Participants)
    20-29 years
    0
    0%
    30-39 years
    0
    0%
    40-49 years
    3
    6.3%
    50-59 years
    10
    20.8%
    60-69 years
    20
    41.7%
    70-79 years
    12
    25%
    80-89 years
    3
    6.3%
    Sex: Female, Male (Count of Participants)
    Female
    48
    100%
    Male
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Incidence of Adverse Effects as Assessed by the National Cancer Institute CTCAE v. 4.0
    Description Adverse Events (Grade 3 or higher)
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Eligible and treated patients
    Arm/Group Title Cediranib
    Arm/Group Description Cediranib (RECENTIN; AZD2171) will be administered PO 30 mg daily. Each 28 day period will be considered a cycle. Treatment will continue until disease progression or adverse effects prohibit further therapy.
    Measure Participants 48
    Leukopenia
    0
    0%
    Thrombocytopenia
    0
    0%
    Neutropenia
    0
    0%
    Anemia
    3
    6.3%
    Other Investigations
    4
    8.3%
    Other Blood/Lymphatics
    1
    2.1%
    Cardiac
    1
    2.1%
    Ear and labyrinth
    0
    0%
    Endocrine
    0
    0%
    Eye
    0
    0%
    Nausea
    1
    2.1%
    Vomiting
    4
    8.3%
    Other Gastrointestinal
    16
    33.3%
    General and administration site
    13
    27.1%
    Hepatobiliary
    0
    0%
    Infections/infestations
    6
    12.5%
    Injury/poisoning
    0
    0%
    Metabolism/nutrition
    8
    16.7%
    Musculoskeletal/connective tissue
    3
    6.3%
    Neoplasms benign/malignant
    4
    8.3%
    Peripheral sensory neuropathy
    0
    0%
    Nervous system
    1
    2.1%
    Psychiatric
    1
    2.1%
    Renal/urinary
    3
    6.3%
    Reproductive/breast
    1
    2.1%
    Respiratory/thoracic/mediastinal
    4
    8.3%
    Skin/subcutaneous
    0
    0%
    Vascular disorders
    18
    37.5%
    2. Primary Outcome
    Title Tumor Response
    Description Complete and Partial Tumor Response by RECIST 1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by 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 For diesease evaluated by physical examination, response was assessed prior to each cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle from enrollment until stopping study therapy. The average time on study is 3 mnths

    Outcome Measure Data

    Analysis Population Description
    Eligible and Treated Patients
    Arm/Group Title Cediranib
    Arm/Group Description Cediranib (RECENTIN; AZD2171) will be administered PO 30 mg daily. Each 28 day period will be considered a cycle. Treatment will continue until disease progression or adverse effects prohibit further therapy.
    Measure Participants 48
    Number (90% Confidence Interval) [percentage of participants]
    12.5
    26%
    3. Primary Outcome
    Title Progression-free Survival (PFS) = > 6 Months
    Description Number of participants who survived for at least 6 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v.1.0) 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 For disease evaluated by physical examination, progression was assessed prior to each cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle. Evaluated from time of enrollment until progression or death, up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Eligible and Treated Patients
    Arm/Group Title Cediranib
    Arm/Group Description Cediranib (RECENTIN; AZD2171) will be administered PO 30 mg daily. Each 28 day period will be considered a cycle. Treatment will continue until disease progression or adverse effects prohibit further therapy.
    Measure Participants 48
    Number (90% Confidence Interval) [percentage of participants]
    33.3
    69.4%
    4. Secondary Outcome
    Title Overall Survival
    Description The observed length of life from entry into the study to death or the date of last contact.
    Time Frame From study entry to death or last contact, up to 5 years.

    Outcome Measure Data

    Analysis Population Description
    Eligible and Treated Patients
    Arm/Group Title Cediranib
    Arm/Group Description Cediranib (RECENTIN; AZD2171) will be administered PO 30 mg daily. Each 28 day period will be considered a cycle. Treatment will continue until disease progression or adverse effects prohibit further therapy.
    Measure Participants 48
    Median (95% Confidence Interval) [months]
    12.5
    5. Secondary Outcome
    Title Progression Free Survival
    Description Time until disease progression, death, or date of last contact.
    Time Frame Disease that can be assessed by physical exam should be evaluated every cycle. disease assessed by imaging should be evaluated every other cycle. Time frame to determine the date of progression is from the date of enrollment up to 5 years after enrollment

    Outcome Measure Data

    Analysis Population Description
    All eligible and evaluable patients
    Arm/Group Title Cediranib
    Arm/Group Description Cediranib (RECENTIN; AZD2171) will be administered PO 30 mg daily. Each 28 day period will be considered a cycle. Treatment will continue until disease progression or adverse effects prohibit further therapy.
    Measure Participants 48
    Median (90% Confidence Interval) [Months]
    3.61
    6. Secondary Outcome
    Title Response Without Regard to the Time of Documented Response
    Description Complete and partial tumor response by RECIST 1.1
    Time Frame Tumor responses with time restriction starts at enrollment and goes to 6 months after enrollment or until pt. off study therapy,whichever occurs first. Without time restriction starts at enrollment,lasts until off study therapy, median duration = 2.63 mth

    Outcome Measure Data

    Analysis Population Description
    Eligible and Treated Patients
    Arm/Group Title Cediranib
    Arm/Group Description Cediranib (RECENTIN; AZD2171) will be administered PO 30 mg daily. Each 28 day period will be considered a cycle. Treatment will continue until disease progression or adverse effects prohibit further therapy.
    Measure Participants 48
    Number (90% Confidence Interval) [percentage of participants]
    12.5
    26%
    7. Other Pre-specified Outcome
    Title Expression of Phosphorylated ERK1 and 2, c-Jun, Stat3, PKC, and p70S6 Kinase
    Description
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Other Pre-specified Outcome
    Title Levels of Receptor Targets Such as VEGFR (1, 2, 3) and PDGFR
    Description
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    9. Other Pre-specified Outcome
    Title Plasma Levels of Endogenous Circulating VEGFA, Levels of Its Endogenous Inhibitor, sFlt-1 (the Truncated, Circulating Portion of VEGFR-1), Circulating TF, and Circulating Par-4
    Description
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    10. Other Pre-specified Outcome
    Title VEGFA Expression on Pre-treatment Tumor Specimens
    Description High vs low expression.
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame All Adverse Events (AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
    Adverse Event Reporting Description
    Arm/Group Title Cediranib
    Arm/Group Description Cediranib (RECENTIN; AZD2171) will be administered PO 30 mg daily. Each 28 day period will be considered a cycle. Treatment will continue until disease progression or adverse effects prohibit further therapy.
    All Cause Mortality
    Cediranib
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Cediranib
    Affected / at Risk (%) # Events
    Total 20/48 (41.7%)
    Blood and lymphatic system disorders
    Anemia 1/48 (2.1%)
    Cardiac disorders
    Myocardial Infarction 1/48 (2.1%)
    Gastrointestinal disorders
    Colonic Perforation 1/48 (2.1%)
    Colitis 1/48 (2.1%)
    Rectal Fistula 1/48 (2.1%)
    Peritoneal Necrosis 1/48 (2.1%)
    Ileal Obstruction 1/48 (2.1%)
    Ascites 1/48 (2.1%)
    General disorders
    Multi-Organ Failure 1/48 (2.1%)
    Death Nos 1/48 (2.1%)
    Infections and infestations
    Lung Infection 1/48 (2.1%)
    Bladder Infection 2/48 (4.2%)
    Investigations
    Alanine Aminotransferase Increased 1/48 (2.1%)
    Metabolism and nutrition disorders
    Dehydration 2/48 (4.2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms Benign, Malignant And Unspecified (Incl 4/48 (8.3%)
    Psychiatric disorders
    Confusion 1/48 (2.1%)
    Renal and urinary disorders
    Urinary Tract Obstruction 1/48 (2.1%)
    Reproductive system and breast disorders
    Pelvic Pain 1/48 (2.1%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 1/48 (2.1%)
    Vascular disorders
    Thromboembolic Event 2/48 (4.2%)
    Other (Not Including Serious) Adverse Events
    Cediranib
    Affected / at Risk (%) # Events
    Total 48/48 (100%)
    Blood and lymphatic system disorders
    Blood And Lymphatic System Disorders - Other 1/48 (2.1%)
    Anemia 17/48 (35.4%)
    Cardiac disorders
    Sinus Bradycardia 1/48 (2.1%)
    Sinus Tachycardia 1/48 (2.1%)
    Chest Pain - Cardiac 1/48 (2.1%)
    Ear and labyrinth disorders
    Middle Ear Inflammation 1/48 (2.1%)
    Vertigo 1/48 (2.1%)
    Tinnitus 3/48 (6.3%)
    Endocrine disorders
    Hypothyroidism 14/48 (29.2%)
    Hyperthyroidism 1/48 (2.1%)
    Endocrine Disorders - Other 1/48 (2.1%)
    Eye disorders
    Eye Disorders - Other 1/48 (2.1%)
    Conjunctivitis 1/48 (2.1%)
    Blurred Vision 3/48 (6.3%)
    Dry Eye 2/48 (4.2%)
    Gastrointestinal disorders
    Dysphagia 1/48 (2.1%)
    Dyspepsia 4/48 (8.3%)
    Dry Mouth 8/48 (16.7%)
    Colitis 1/48 (2.1%)
    Constipation 13/48 (27.1%)
    Diarrhea 33/48 (68.8%)
    Vomiting 15/48 (31.3%)
    Anal Hemorrhage 1/48 (2.1%)
    Abdominal Pain 11/48 (22.9%)
    Rectal Hemorrhage 2/48 (4.2%)
    Oral Dysesthesia 1/48 (2.1%)
    Mucositis Oral 14/48 (29.2%)
    Oral Hemorrhage 1/48 (2.1%)
    Gastrointestinal Pain 1/48 (2.1%)
    Gastric Hemorrhage 1/48 (2.1%)
    Oral Pain 5/48 (10.4%)
    Abdominal Distension 2/48 (4.2%)
    Nausea 22/48 (45.8%)
    Gastric Ulcer 1/48 (2.1%)
    Gastroesophageal Reflux Disease 2/48 (4.2%)
    Rectal Pain 1/48 (2.1%)
    Fecal Incontinence 2/48 (4.2%)
    Ascites 1/48 (2.1%)
    Esophageal Pain 1/48 (2.1%)
    Flatulence 2/48 (4.2%)
    General disorders
    General Disorders And Administration Site Conditio 1/48 (2.1%)
    Pain 10/48 (20.8%)
    Flu Like Symptoms 1/48 (2.1%)
    Edema Limbs 2/48 (4.2%)
    Edema Face 1/48 (2.1%)
    Fatigue 39/48 (81.3%)
    Fever 3/48 (6.3%)
    Gait Disturbance 1/48 (2.1%)
    Chills 1/48 (2.1%)
    Hepatobiliary disorders
    Gallbladder Pain 1/48 (2.1%)
    Infections and infestations
    Upper Respiratory Infection 2/48 (4.2%)
    Skin Infection 1/48 (2.1%)
    Urinary Tract Infection 10/48 (20.8%)
    Injury, poisoning and procedural complications
    Bruising 3/48 (6.3%)
    Investigations
    Investigations - Other 1/48 (2.1%)
    Weight Loss 16/48 (33.3%)
    Platelet Count Decreased 11/48 (22.9%)
    Lymphocyte Count Decreased 1/48 (2.1%)
    Lipase Increased 1/48 (2.1%)
    Inr Increased 2/48 (4.2%)
    Hemoglobin Increased 1/48 (2.1%)
    Creatinine Increased 11/48 (22.9%)
    Cholesterol High 1/48 (2.1%)
    Neutrophil Count Decreased 4/48 (8.3%)
    Blood Bilirubin Increased 1/48 (2.1%)
    White Blood Cell Decreased 11/48 (22.9%)
    Aspartate Aminotransferase Increased 12/48 (25%)
    Alkaline Phosphatase Increased 7/48 (14.6%)
    Alanine Aminotransferase Increased 9/48 (18.8%)
    Activated Partial Thromboplastin Time Prolonged 2/48 (4.2%)
    Metabolism and nutrition disorders
    Hypophosphatemia 2/48 (4.2%)
    Hyponatremia 10/48 (20.8%)
    Hypomagnesemia 9/48 (18.8%)
    Hypokalemia 9/48 (18.8%)
    Hypoglycemia 3/48 (6.3%)
    Hypocalcemia 7/48 (14.6%)
    Hypoalbuminemia 9/48 (18.8%)
    Hypernatremia 2/48 (4.2%)
    Hyperkalemia 2/48 (4.2%)
    Hyperglycemia 8/48 (16.7%)
    Dehydration 5/48 (10.4%)
    Anorexia 23/48 (47.9%)
    Acidosis 1/48 (2.1%)
    Musculoskeletal and connective tissue disorders
    Pain In Extremity 1/48 (2.1%)
    Neck Pain 1/48 (2.1%)
    Myalgia 6/48 (12.5%)
    Muscle Weakness Lower Limb 1/48 (2.1%)
    Joint Range Of Motion Decreased 1/48 (2.1%)
    Generalized Muscle Weakness 3/48 (6.3%)
    Flank Pain 1/48 (2.1%)
    Chest Wall Pain 1/48 (2.1%)
    Back Pain 4/48 (8.3%)
    Arthralgia 4/48 (8.3%)
    Nervous system disorders
    Reversible Posterior Leukoencephalopathy Syndrome 1/48 (2.1%)
    Peripheral Sensory Neuropathy 15/48 (31.3%)
    Peripheral Motor Neuropathy 1/48 (2.1%)
    Memory Impairment 1/48 (2.1%)
    Intracranial Hemorrhage 1/48 (2.1%)
    Headache 11/48 (22.9%)
    Dysgeusia 2/48 (4.2%)
    Syncope 1/48 (2.1%)
    Dizziness 5/48 (10.4%)
    Depressed Level Of Consciousness 1/48 (2.1%)
    Cognitive Disturbance 2/48 (4.2%)
    Psychiatric disorders
    Insomnia 3/48 (6.3%)
    Depression 1/48 (2.1%)
    Anxiety 4/48 (8.3%)
    Renal and urinary disorders
    Urinary Tract Obstruction 1/48 (2.1%)
    Urinary Tract Pain 1/48 (2.1%)
    Proteinuria 10/48 (20.8%)
    Hematuria 1/48 (2.1%)
    Acute Kidney Injury 1/48 (2.1%)
    Reproductive system and breast disorders
    Vaginal Pain 1/48 (2.1%)
    Vaginal Hemorrhage 1/48 (2.1%)
    Vaginal Dryness 1/48 (2.1%)
    Pelvic Pain 2/48 (4.2%)
    Breast Pain 1/48 (2.1%)
    Respiratory, thoracic and mediastinal disorders
    Voice Alteration 5/48 (10.4%)
    Respiratory Failure 1/48 (2.1%)
    Nasal Congestion 1/48 (2.1%)
    Pleuritic Pain 1/48 (2.1%)
    Hoarseness 4/48 (8.3%)
    Epistaxis 2/48 (4.2%)
    Dyspnea 7/48 (14.6%)
    Cough 3/48 (6.3%)
    Allergic Rhinitis 1/48 (2.1%)
    Skin and subcutaneous tissue disorders
    Skin And Subcutaneous Tissue Disorders - Other 2/48 (4.2%)
    Skin Induration 1/48 (2.1%)
    Pruritus 1/48 (2.1%)
    Palmar-Plantar Erythrodysesthesia Syndrome 4/48 (8.3%)
    Rash Maculo-Papular 2/48 (4.2%)
    Dry Skin 3/48 (6.3%)
    Bullous Dermatitis 1/48 (2.1%)
    Alopecia 2/48 (4.2%)
    Vascular disorders
    Thromboembolic Event 3/48 (6.3%)
    Hypotension 1/48 (2.1%)
    Hypertension 29/48 (60.4%)
    Hot Flashes 1/48 (2.1%)
    Hematoma 1/48 (2.1%)

    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 Linda Gedeon for Michael Sill, PhD
    Organization NRG Oncology /GOG
    Phone 716 845-1169
    Email lgedeon@gogstats.org
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01132820
    Other Study ID Numbers:
    • NCI-2011-02043
    • NCI-2011-02043
    • GOG-0229J
    • CDR0000674008
    • GOG-0229J
    • GOG-0229J
    • U10CA180868
    • U10CA027469
    First Posted:
    May 28, 2010
    Last Update Posted:
    Aug 8, 2019
    Last Verified:
    Aug 1, 2019