Selumetinib Sulfate in Treating Woman With Recurrent Low-Grade Ovarian Cancer or Peritoneum Cancer

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00551070
Collaborator
NRG Oncology (Other)
52
49
1
154.9
1.1
0

Study Details

Study Description

Brief Summary

This phase II trial studies the side effects and how well selumetinib sulfate works in treating patients with low-grade ovarian cancer that has come back (recurrent). Selumetinib sulfate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES:
  1. To examine the tumor response rate of patients on AZD6244 (selumetinib sulfate) (NSC #748727).

  2. To examine the acute toxicity of AZD6244 (NSC #748727) during the first course of treatment using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  3. To define the pharmacokinetic profile for AZD6244, 100 mg administered orally twice daily.

SECONDARY OBJECTIVES:
  1. To examine the toxicity of AZD6244 (NSC #748727) using the 21 major categories of the CTCAE version 3.0.

  2. To examine the dose and number of courses of AZD6244 (NSC #748727) given. III. To estimate the progression free survival, and overall survival of women receiving AZD6244 (NSC #748727).

TRANSLATIONAL RESEARCH OBJECTIVES:
  1. To examine deoxyribonucleic acid (DNA) isolation with sequencing of braf, and ras mutation analysis and to explore their relationship with tumor response with AZD6244 (NSC #748727).

  2. To examine protein levels of phosphorylated (p)-ERK/ERKERK) and explore their relationship with tumor response in patients treated with AZD6244 (NSC #748727).

OUTLINE:

Patients receive selumetinib sulfate orally (PO) twice a day (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection periodically for correlative and pharmacokinetic studies and to analyze selumetinib sulfate peak concentrations and the corresponding peak time values. Previously collected archived tumor tissue samples are obtained to determine protein levels of p-ERK/ERKERK, DNA isolation and sequencing of BRAF and ras mutation analysis by immunohistochemistry (IHC).

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then once a year for 5 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
52 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Trial of AZD6244 (NSC# 748727) in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary or Peritoneum
Actual Study Start Date :
Dec 17, 2007
Actual Primary Completion Date :
Jul 23, 2013
Actual Study Completion Date :
Nov 13, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (selumetinib sulfate)

Patients receive selumetinib sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

Drug: Selumetinib
Given PO
Other Names:
  • ARRY-142886
  • AZD6244
  • MEK Inhibitor AZD6244
  • Drug: Selumetinib Sulfate
    Given PO
    Other Names:
  • AZD-6244 Hydrogen Sulfate
  • AZD6244 Hydrogen Sulfate
  • AZD6244 Hydrogen Sulphate
  • Koselugo
  • Selumetinib Sulphate
  • Outcome Measures

    Primary Outcome Measures

    1. Tumor Response [Every other cycle]

      Complete and Partial Tumor Response by (Response Evaluation Criteria in Solid Tumors) RECIST 1.0

    2. Adverse Events (Grade 3 or Higher) During First Cycle of Treatment [Cycle 1]

    3. Area Under the Curve (AUC) for AZD6244, 100 mg Administered Orally Twice Daily. [Pre-dose, and 1, 3, and 6 hours after administration of drug on Day 7 after the start of AZD6244 treatment]

    4. Maximum Concentration (Cmax) for AZD6244, 100 mg Administered Orally Twice Daily. [Pre-dose, and 1, 3, and 6 hours after administration of drug on Day 7 after the start of AZD6244 treatment]

    Secondary Outcome Measures

    1. Progression-free Survival [Every other cycle]

    2. Number of Courses Received [Every cycle]

    3. Overall Survival [Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    19 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients age greater than 18 with the following tumors are included in the study:

    • Patients initially diagnosed with low-grade serous ovarian or peritoneal carcinoma that recur as low grade serous carcinoma (invasive micropapillary serous carcinoma or invasive grade I serous carcinomas as defined by Gynecologic Oncology Group [GOG], International Federation of Gynecology and Obstetrics [FIGO] World Health Organization [WHO] or Silverberg)

    • Patients initially diagnosed with serous borderline ovarian or peritoneal carcinoma that recur as low grade serous carcinoma (invasive micropapillary serous carcinoma or invasive grade I serous carcinomas as defined by GOG, FIGO WHO or Silverberg)

    • Patients must have measurable disease:

    • Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each "target" lesion must be >= 20 mm when measured by conventional techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or >= 10 mm when measured by spiral CT

    • Patient must have documented low grade serous carcinoma (invasive micropapillary serous); confirmation must occur before patient is considered eligible for the trial

    • Patients whose primary tumor was low-grade serous ovarian or peritoneal carcinoma must have a pretreatment sample of their tumor from their primary or recurrent tumor that documents low grade serous carcinoma (invasive micropapillary serous)

    • Patients whose primary tumor was serous borderline ovarian or peritoneal carcinoma must have a pretreatment sample of their tumor from their recurrent tumor that documents low grade serous carcinoma (invasive micropapillary serous)

    • Creatinine CTCAE grade 0-1 (< 1.5 x upper limit of normal [ULN])

    • Bilirubin CTCAE grade 0-1 (< 1.5 x ULN)

    • Transaminases CTCAE grade 0-1 (< 2.5 x ULN)

    • Neutrophil CTCAE grade 0-1 (>= 1500/mcl)

    • Platelets CTCAE grade 0-1 (>= 100,000/mcl)

    • Neuropathy =< CTCAE grade 1

    • No restrictions on prior therapy; patients cannot have previously received AZD6244

    • Patients of childbearing potential must have a negative pregnancy test and must agree to practice an effective means of birth control prior to study entry, for the duration of study participation, and for four weeks after dosing with AZD6244 ceases

    • Patients who have met the pre-entry requirements

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

    • Patients must have a GOG performance status of 0 or 1

    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

    • Patients may not be receiving any other investigational agents

    • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events

    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244 or its excipient Captisol

    • Previous mitogen-activated protein kinase (MEK) inhibitor use

    • Patients with corrected QT (QTc) interval > 450 msecs or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) including heart failure that meets New York Heart Association (NYHA) class III and IV definitions are excluded

    • Required use of a concomitant medication that can prolong the QT interval

    • Patients should not receive any drugs known to affect or with the potential to affect selected CYP450 isoenzymes

    • Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption

    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements

    • Pregnant women are excluded from this study because the effects of AZD6244 on the developing human fetus at the recommended therapeutic dose are unknown; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with AZD6244

    • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD6244; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 USC / Norris Comprehensive Cancer Center Los Angeles California United States 90033
    2 Stanford Cancer Institute Palo Alto Palo Alto California United States 94304
    3 Hartford Hospital Hartford Connecticut United States 06102
    4 The Hospital of Central Connecticut New Britain Connecticut United States 06050
    5 Beebe Medical Center Lewes Delaware United States 19958
    6 Christiana Care Health System-Christiana Hospital Newark Delaware United States 19718
    7 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
    8 Hinsdale Hematology Oncology Associates Incorporated Hinsdale Illinois United States 60521
    9 Saint Vincent Hospital and Health Care Center Indianapolis Indiana United States 46260
    10 Maine Medical Center-Bramhall Campus Portland Maine United States 04102
    11 Christiana Care - Union Hospital Elkton Maryland United States 21921
    12 Massachusetts General Hospital Cancer Center Boston Massachusetts United States 02114
    13 Brigham and Women's Hospital Boston Massachusetts United States 02115
    14 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    15 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    16 Bronson Battle Creek Battle Creek Michigan United States 49017
    17 Spectrum Health Big Rapids Hospital Big Rapids Michigan United States 49307
    18 Cancer Research Consortium of West Michigan NCORP Grand Rapids Michigan United States 49503
    19 Mercy Health Saint Mary's Grand Rapids Michigan United States 49503
    20 Spectrum Health at Butterworth Campus Grand Rapids Michigan United States 49503
    21 Holland Community Hospital Holland Michigan United States 49423
    22 Mercy Health Partners-Hackley Campus Muskegon Michigan United States 49442
    23 Mercy Health Mercy Campus Muskegon Michigan United States 49444
    24 Munson Medical Center Traverse City Michigan United States 49684
    25 Metro Health Hospital Wyoming Michigan United States 49519
    26 University of Mississippi Medical Center Jackson Mississippi United States 39216
    27 Washington University School of Medicine Saint Louis Missouri United States 63110
    28 Cancer Research for the Ozarks NCORP Springfield Missouri United States 65804
    29 Mercy Hospital Springfield Springfield Missouri United States 65804
    30 CoxHealth South Hospital Springfield Missouri United States 65807
    31 Cooper Hospital University Medical Center Camden New Jersey United States 08103
    32 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    33 Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina United States 28203
    34 Novant Health Presbyterian Medical Center Charlotte North Carolina United States 28204
    35 Gynecologic Oncology Network Greenville North Carolina United States 27834
    36 Case Western Reserve University Cleveland Ohio United States 44106
    37 MetroHealth Medical Center Cleveland Ohio United States 44109
    38 Cleveland Clinic Cancer Center/Fairview Hospital Cleveland Ohio United States 44111
    39 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    40 Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210
    41 Riverside Methodist Hospital Columbus Ohio United States 43214
    42 Mount Carmel Health Center West Columbus Ohio United States 43222
    43 Miami Valley Hospital Dayton Ohio United States 45409
    44 Hillcrest Hospital Cancer Center Mayfield Heights Ohio United States 44124
    45 UH Seidman Cancer Center at Lake Health Mentor Campus Mentor Ohio United States 44060
    46 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    47 Oklahoma Cancer Specialists and Research Institute-Tulsa Tulsa Oklahoma United States 74146
    48 Abington Memorial Hospital Abington Pennsylvania United States 19001
    49 M D Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • National Cancer Institute (NCI)
    • NRG Oncology

    Investigators

    • Principal Investigator: John H Farley, NRG Oncology

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00551070
    Other Study ID Numbers:
    • NCI-2009-00604
    • NCI-2009-00604
    • CDR0000563965
    • GOG-0239
    • GOG-0239
    • U10CA180868
    • U10CA027469
    First Posted:
    Oct 30, 2007
    Last Update Posted:
    Dec 3, 2020
    Last Verified:
    Nov 1, 2020

    Study Results

    Participant Flow

    Recruitment Details The study was activated on 9/22/2008 and closed to accrual on 1/31/2011 (suspended from 1/4/2010 to 8/9/2010).
    Pre-assignment Detail
    Arm/Group Title AZD6244
    Arm/Group Description AZD6244 (NSC #748727) 100 mg orally BID until disease progression or adverse effects prohibit further therapy (1 cycle =28 days)
    Period Title: Overall Study
    STARTED 52
    COMPLETED 52
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title AZD6244
    Arm/Group Description AZD6244 (NSC #748727) 100 mg orally BID until disease progression or adverse effects prohibit further therapy (1 cycle =28 days)
    Overall Participants 52
    Age, Customized (participants) [Number]
    20-29 years
    3
    5.8%
    30-39 years
    11
    21.2%
    40-49 years
    8
    15.4%
    50-59 years
    17
    32.7%
    60-69 years
    9
    17.3%
    70-79 years
    4
    7.7%
    80-89 years
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    52
    100%
    Male
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Tumor Response
    Description Complete and Partial Tumor Response by (Response Evaluation Criteria in Solid Tumors) RECIST 1.0
    Time Frame Every other cycle

    Outcome Measure Data

    Analysis Population Description
    Eligible and treated patients
    Arm/Group Title AZD6244
    Arm/Group Description AZD6244 (NSC #748727) 100 mg orally BID until disease progression or adverse effects prohibit further therapy (1 cycle =28 days)
    Measure Participants 52
    Number (90% Confidence Interval) [percentage of patients]
    15.4
    2. Secondary Outcome
    Title Progression-free Survival
    Description
    Time Frame Every other cycle

    Outcome Measure Data

    Analysis Population Description
    Eligible and Treated Patients
    Arm/Group Title AZD6244
    Arm/Group Description AZD6244 (NSC #748727) 100 mg orally BID until disease progression or adverse effects prohibit further therapy (1 cycle =28 days)
    Measure Participants 52
    Median (95% Confidence Interval) [months]
    11.3
    3. Secondary Outcome
    Title Number of Courses Received
    Description
    Time Frame Every cycle

    Outcome Measure Data

    Analysis Population Description
    Eligible and Treated Patients. Two patients still on study and have received 68 and 79 cycles of treatment.
    Arm/Group Title AZD6244
    Arm/Group Description AZD6244 (NSC #748727) 100 mg orally BID until disease progression or adverse effects prohibit further therapy (1 cycle =28 days)
    Measure Participants 52
    Median (Inter-Quartile Range) [courses]
    5
    4. Primary Outcome
    Title Adverse Events (Grade 3 or Higher) During First Cycle of Treatment
    Description
    Time Frame Cycle 1

    Outcome Measure Data

    Analysis Population Description
    Eligible and treated patients.
    Arm/Group Title AZD6244
    Arm/Group Description AZD6244 (NSC #748727) 100 mg orally BID until disease progression or adverse effects prohibit further therapy (1 cycle =28 days)
    Measure Participants 52
    Leukopenia
    0
    Thrombocytopenia
    0
    Neutropenia
    0
    Anemia
    2
    Allergy/Immunology
    0
    Auditory/Ear
    0
    Cardiac
    2
    Coagulation
    0
    Constitutional
    4
    Dermatologic
    12
    Gastrointestinal
    13
    Genitourinary/Renal
    2
    Hemorrhage
    0
    Infection
    0
    Lymphatics
    0
    Metabolic
    0
    Musculoskeletal
    0
    Neurosensory
    0
    Other Neurological
    0
    Ocular/Visual
    0
    Pain
    4
    Pulmonary
    4
    5. Primary Outcome
    Title Area Under the Curve (AUC) for AZD6244, 100 mg Administered Orally Twice Daily.
    Description
    Time Frame Pre-dose, and 1, 3, and 6 hours after administration of drug on Day 7 after the start of AZD6244 treatment

    Outcome Measure Data

    Analysis Population Description
    Eligible and Treated Patients with all pharmacokinetic time points available
    Arm/Group Title AZD6244
    Arm/Group Description AZD6244 (NSC #748727) 100 mg orally BID until disease progression or adverse effects prohibit further therapy (1 cycle =28 days)
    Measure Participants 41
    Median (Inter-Quartile Range) [ng x hr/mL]
    2419
    6. Primary Outcome
    Title Maximum Concentration (Cmax) for AZD6244, 100 mg Administered Orally Twice Daily.
    Description
    Time Frame Pre-dose, and 1, 3, and 6 hours after administration of drug on Day 7 after the start of AZD6244 treatment

    Outcome Measure Data

    Analysis Population Description
    Eligible and Treated Patients with at least one post-dose pharmacokinetic time point available
    Arm/Group Title AZD6244
    Arm/Group Description AZD6244 (NSC #748727) 100 mg orally BID until disease progression or adverse effects prohibit further therapy (1 cycle =28 days)
    Measure Participants 42
    Median (Inter-Quartile Range) [ng/mL]
    585
    7. Secondary Outcome
    Title Overall Survival
    Description
    Time Frame Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years

    Outcome Measure Data

    Analysis Population Description
    Eligible and Treated Patients
    Arm/Group Title AZD6244
    Arm/Group Description AZD6244 (NSC #748727) 100 mg orally BID until disease progression or adverse effects prohibit further therapy (1 cycle =28 days)
    Measure Participants 52
    Median (95% Confidence Interval) [Months]
    32.4

    Adverse Events

    Time Frame Study Treatment
    Adverse Event Reporting Description Includes all adverse events reported (grade 1-5) regardless of attribution.
    Arm/Group Title AZD6244
    Arm/Group Description AZD6244 (NSC #748727) 100 mg orally BID until disease progression or adverse effects prohibit further therapy (1 cycle =28 days)
    All Cause Mortality
    AZD6244
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    AZD6244
    Affected / at Risk (%) # Events
    Total 33/52 (63.5%)
    Blood and lymphatic system disorders
    Leukocytes 1/52 (1.9%)
    Hemoglobin 1/52 (1.9%)
    Edema: Limb 1/52 (1.9%)
    Cardiac disorders
    Prolonged Qtc Interval 1/52 (1.9%)
    S/N Arrhythmia: Sinus Bradycardia 1/52 (1.9%)
    Hypertension 2/52 (3.8%)
    Hypotension 1/52 (1.9%)
    Gastrointestinal disorders
    Ulcer,gi - Esophagus 1/52 (1.9%)
    Obstruction, Gi - Colon 2/52 (3.8%)
    Mucositis (Functional/Sympt) - Oral Cavity 2/52 (3.8%)
    Obstruction, Gi - Small Bowel Nos 4/52 (7.7%)
    Mucositis (Clinical Exam) - Oral Cavity 3/52 (5.8%)
    Vomiting 1/52 (1.9%)
    Dehydration 2/52 (3.8%)
    Constipation 1/52 (1.9%)
    Nausea 2/52 (3.8%)
    Gastrointestinal - Other 1/52 (1.9%)
    Stricture, Gi - Biliary Tree 1/52 (1.9%)
    General disorders
    Weight Gain 2/52 (3.8%)
    Death No Ctcae Term - Disease Progression Nos 1/52 (1.9%)
    Pain: Throat/Pharynx/Larynx 1/52 (1.9%)
    Pain: Back 1/52 (1.9%)
    Pain: Abdominal Pain Nos 4/52 (7.7%)
    Infections and infestations
    Inf W/Nml Or Gr 1 Or 2 Anc: Lung(Pneumonia) 1/52 (1.9%)
    Inf W/Nml Or Gr 1 Or 2 Anc: Skin(Cellulitis) 2/52 (3.8%)
    Inf Unknown Anc: Wound 1/52 (1.9%)
    Metabolism and nutrition disorders
    Alt 2/52 (3.8%)
    Alkaline Phosphatase 1/52 (1.9%)
    Nervous system disorders
    Syncope 1/52 (1.9%)
    Mood Alteration - Depression 1/52 (1.9%)
    Respiratory, thoracic and mediastinal disorders
    Ards 1/52 (1.9%)
    Vascular disorders
    Hemorrhage, Gi - Rectum 1/52 (1.9%)
    Thrombosis/Thrombus/Embolism 1/52 (1.9%)
    Other (Not Including Serious) Adverse Events
    AZD6244
    Affected / at Risk (%) # Events
    Total 52/52 (100%)
    Blood and lymphatic system disorders
    Neutrophils 10/52 (19.2%)
    Platelets 6/52 (11.5%)
    Blood/Bone Marrow - Other 1/52 (1.9%)
    Leukocytes 11/52 (21.2%)
    Hemoglobin 28/52 (53.8%)
    Lymphocele 1/52 (1.9%)
    Edema: Limb 24/52 (46.2%)
    Edema: Head And Neck 4/52 (7.7%)
    Cardiac disorders
    Prolonged Qtc Interval 1/52 (1.9%)
    Palpitations 1/52 (1.9%)
    S/N Arrhythmia: Sinus Bradycardia 1/52 (1.9%)
    Hypertension 5/52 (9.6%)
    Ear and labyrinth disorders
    Tinnitus 4/52 (7.7%)
    Endocrine disorders
    Hot Flashes 1/52 (1.9%)
    Eye disorders
    Ocular/Visual - Other 2/52 (3.8%)
    Watery Eye 1/52 (1.9%)
    Dry Eye 2/52 (3.8%)
    Blurred Vision 4/52 (7.7%)
    Gastrointestinal disorders
    Obstruction, Gi - Ileum 1/52 (1.9%)
    Flatulence 1/52 (1.9%)
    Gastritis 2/52 (3.8%)
    Hemorrhoids 2/52 (3.8%)
    Heartburn 3/52 (5.8%)
    Dysphagia 2/52 (3.8%)
    Distention 4/52 (7.7%)
    Taste Alteration 2/52 (3.8%)
    Dry Mouth 4/52 (7.7%)
    Mucositis (Functional/Sympt) - Oral Cavity 3/52 (5.8%)
    Colitis 1/52 (1.9%)
    Mucositis (Clinical Exam) - Oral Cavity 9/52 (17.3%)
    Mucositis (Clinical Exam) - Esophagus 1/52 (1.9%)
    Vomiting 25/52 (48.1%)
    Anorexia 12/52 (23.1%)
    Dehydration 3/52 (5.8%)
    Constipation 16/52 (30.8%)
    Nausea 35/52 (67.3%)
    Gastrointestinal - Other 2/52 (3.8%)
    Diarrhea 41/52 (78.8%)
    General disorders
    Constitutional Symptoms - Other 2/52 (3.8%)
    Sweating 1/52 (1.9%)
    Weight Gain 11/52 (21.2%)
    Fever 5/52 (9.6%)
    Weight Loss 2/52 (3.8%)
    Rigors/Chills 3/52 (5.8%)
    Fatigue 39/52 (75%)
    Insomnia 6/52 (11.5%)
    Pain - Other 2/52 (3.8%)
    Pain: Urethra 1/52 (1.9%)
    Pain: Chest /Thorax Nos 1/52 (1.9%)
    Pain: Throat/Pharynx/Larynx 3/52 (5.8%)
    Pain: Head/Headache 9/52 (17.3%)
    Pain: Neck 1/52 (1.9%)
    Pain: Intestine 1/52 (1.9%)
    Pain: Extremity-Limb 8/52 (15.4%)
    Pain: Back 7/52 (13.5%)
    Pain: Joint 5/52 (9.6%)
    Pain: Bladder 1/52 (1.9%)
    Pain: Pain Nos 1/52 (1.9%)
    Pain: Abdominal Pain Nos 20/52 (38.5%)
    Pain: Skin 1/52 (1.9%)
    Pain: Cardiac/ Heart 1/52 (1.9%)
    Pain: Muscle 5/52 (9.6%)
    Pain: Anus 1/52 (1.9%)
    Pain: Sinus 1/52 (1.9%)
    Immune system disorders
    Allergic Reaction/Hypersensitivity 1/52 (1.9%)
    Rhinitis 2/52 (3.8%)
    Infections and infestations
    Inf W/Nml Or Gr 1 Or 2 Anc: Vulva 1/52 (1.9%)
    Inf W/Nml Or Gr 1 Or 2 Anc: Upper Airway Nos 2/52 (3.8%)
    Inf W/Nml Or Gr 1 Or 2 Anc: Wound 1/52 (1.9%)
    Inf W/Nml Or Gr 1 Or 2 Anc: Skin(Cellulitis) 2/52 (3.8%)
    Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos 4/52 (7.7%)
    Inf W/Nml Or Gr 1 Or 2 Anc: Ungual (Nails) 2/52 (3.8%)
    Infection - Other 3/52 (5.8%)
    Inf W/Nml Or Gr 1 Or 2 Anc: Pharynx 1/52 (1.9%)
    Inf W/Nml Or Gr 1 Or 2 Anc: Vagina 1/52 (1.9%)
    Inf Unknown Anc: Pharynx 1/52 (1.9%)
    Inf Unknown Anc: Bronchus 1/52 (1.9%)
    Inf Unknown Anc: Skin (Cellulitis) 1/52 (1.9%)
    Inf W/Nml Or Gr 1 Or 2 Anc: Bladder 2/52 (3.8%)
    Metabolism and nutrition disorders
    Ast 24/52 (46.2%)
    Metabolic/Laboratory - Other 5/52 (9.6%)
    Proteinuria 2/52 (3.8%)
    Creatinine 8/52 (15.4%)
    Hypoalbuminemia 12/52 (23.1%)
    Ggt 1/52 (1.9%)
    Alt 20/52 (38.5%)
    Alkaline Phosphatase 16/52 (30.8%)
    Bilirubin 3/52 (5.8%)
    Hypophosphatemia 2/52 (3.8%)
    Hyponatremia 7/52 (13.5%)
    Hypernatremia 2/52 (3.8%)
    Hypocalcemia 5/52 (9.6%)
    Hyperkalemia 2/52 (3.8%)
    Hyperglycemia 9/52 (17.3%)
    Hypokalemia 12/52 (23.1%)
    Hypoglycemia 2/52 (3.8%)
    Hypercalcemia 3/52 (5.8%)
    Hypomagnesemia 18/52 (34.6%)
    Musculoskeletal and connective tissue disorders
    Arthritis 1/52 (1.9%)
    Muscle Weakness - Whole Body/Generalized 1/52 (1.9%)
    Nervous system disorders
    Neurology - Other 1/52 (1.9%)
    Mood Alteration - Depression 5/52 (9.6%)
    Mood Alteration - Anxiety 9/52 (17.3%)
    Tremor 1/52 (1.9%)
    Speech Impairment 1/52 (1.9%)
    Cognitive Disturbance 1/52 (1.9%)
    Memory Impairment 1/52 (1.9%)
    Dizziness 3/52 (5.8%)
    Neuropathy-Sensory 20/52 (38.5%)
    Renal and urinary disorders
    Renal/Genitourinary - Other 1/52 (1.9%)
    Obstruction, Gu - Ureter 1/52 (1.9%)
    Incontinence, Urinary 1/52 (1.9%)
    Urinary Frequency 2/52 (3.8%)
    Reproductive system and breast disorders
    Vaginal Discharge 1/52 (1.9%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary: Other 1/52 (1.9%)
    Bronchospasm 1/52 (1.9%)
    Voice Changes 1/52 (1.9%)
    Cough 4/52 (7.7%)
    Dyspnea 16/52 (30.8%)
    Skin and subcutaneous tissue disorders
    Nail Changes 3/52 (5.8%)
    Photosensitivity 1/52 (1.9%)
    Hair Loss/Alopecia (Scalp Or Body) 10/52 (19.2%)
    Hypopigmentation 1/52 (1.9%)
    Acne 9/52 (17.3%)
    Rash 31/52 (59.6%)
    Dry Skin 9/52 (17.3%)
    Pruritus 4/52 (7.7%)
    Urticaria 1/52 (1.9%)
    Flushing 2/52 (3.8%)
    Hand-Foot 2/52 (3.8%)
    Dermatology/Skin - Other 1/52 (1.9%)
    Ulceration 1/52 (1.9%)
    Vascular disorders
    Inr 2/52 (3.8%)
    Hemorrhage, Gu - Urinary Nos 3/52 (5.8%)
    Hemorrhage, Gu - Vagina 2/52 (3.8%)
    Hemorrhage/Pulmonary - Bronchopulmonary Nos 1/52 (1.9%)
    Hemorrhage, Gi - Rectum 2/52 (3.8%)
    Hemorrhage/Pulmonary - Nose 1/52 (1.9%)
    Hemorrhage, Gi - Oral Cavity 1/52 (1.9%)
    Hemorrhage, Gu - Bladder 4/52 (7.7%)
    Hemorrhage, Gi - Colon 1/52 (1.9%)
    Thrombosis/Thrombus/Embolism 1/52 (1.9%)

    Limitations/Caveats

    Study began with 100mg BID mix & drink (MD) formulation. AstraZeneca (AZ) switched to hydrogen-sulfate capsule (HC). AZ deemed 100mg BID MD equivalent to 50mg BID HC. As of 12/31/2010, patients got 50mg BID HC; four patients were on treatment then.

    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 Angela M. Kuras, Associate Director of Data Management
    Organization NRG Oncology Statistics and Data Management Center - Buffalo
    Phone 716-845-7733
    Email kurasa@nrgoncology.org
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00551070
    Other Study ID Numbers:
    • NCI-2009-00604
    • NCI-2009-00604
    • CDR0000563965
    • GOG-0239
    • GOG-0239
    • U10CA180868
    • U10CA027469
    First Posted:
    Oct 30, 2007
    Last Update Posted:
    Dec 3, 2020
    Last Verified:
    Nov 1, 2020