Sorafenib and Bevacizumab to Treat Ovarian, Fallopian and Peritoneal Cancer

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00436215
Collaborator
(none)
55
1
1
93.5
0.6

Study Details

Study Description

Brief Summary

Background:
  • Sorafenib and bevacizumab are anti-cancer drugs that work by targeting the blood vessels that allow tumors to grow. Using the two drugs together may more effectively block the formation of blood vessels that feed tumors.

  • Sorafenib and bevacizumab both are approved by the Food and Drug Administration for use in other cancers but have not ovarian cancer. In a preliminary trial of this drug combination, however, tumors in 6 of 14 patients with ovarian cancer shrank.

Objectives:
  • To determine the safety and activity of the combination of sorafenib and bevacizumab for treating patients with ovarian, fallopian and peritoneal cancer.

  • To determine how sorafenib and bevacizumab may affect the cancer by measuring amounts of different proteins in small biopsy samples of tumor taken before starting treatment and after 6 weeks.

Eligibility:
  • Females 18 years of age and older with ovarian, fallopian, or peritoneal cancer whose disease has not responded to standard treatment or for which no standard treatment is available.

  • Patients must have not been previously treated with bevacizumab or must have had their disease worsen while taking bevacizumab-based therapy.

Design:
  • Patients take 200 mg of sorafenib by mouth twice a day Monday through Friday each week and 5 mg/kg of bevacizumab through a vein every 2 weeks.

  • Tumor biopsies and imaging scans (magnetic resonance imaging (MRI) and positron emission tomography (PET) are done before treatment, 3 days after beginning treatment, and 6 weeks into therapy.

  • Computed tomography (CT) or other imaging tests are done every 8 weeks to evaluate response to treatment.

  • History, physical examinations, blood and urine tests are done periodically during treatment for health checks and research purposes.

  • About 74 patients are to be enrolled in the trial.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Background:

Sorafenib is an inhibitor of wild-type and mutant proto-oncogene BRaf (B-Raf) and proto-oncogene c-Raf (c-Raf) kinase isoforms in vitro, but it also inhibits mitogen-activated protein kinase (p38), proto-oncogene c-kit (c-kit), vascular endothelial growth factor receptor 2 (VEGFR-2) and platelet-derived growth factor (PDGFR)-Beta affecting tumor growth as well as possibly promoting apoptosis by events downstream of c-Raf.

Bevacizumab is a humanized immunoglobulin G 1 (IgG1) monoclonal antibody (MAb) that binds all biologically active isoforms of human vascular endothelial growth factor (vascular endothelial growth factor (VEGF), or VEGF-A) with high affinity (kd = 1.1nM).

Phase I trial of sorafenib and bevacizumab administered concurrently showed activity of the combination in patients with refractory ovarian cancer.

Objectives:

Determine the activity and tolerability of the combination bevacizumab and sorafenib in patients with refractory or recurrent epithelial ovarian, fallopian, or peritoneal cancer in patients who are bevacizumab-naive or bevacizumab-resistant.

Eligibility:

Adults with histologically documented refractory or recurrent epithelial ovarian, fallopian, or peritoneal cancer.

Patients must be off prior chemotherapy, radiation therapy, hormonal therapy, or biological therapy for at least 4 weeks.

Patients must have an Eastern Cooperative Oncology Group (ECOG) of 1 or less.

Patients must have disease that is amenable to biopsy.

Patients must have not been previously treated with bevacizumab or must have progressed on prior bevacizumab-based therapy.

Design:

Patients will be stratified on entrance to the trial based on their previous exposure to bevacizumab to either strata A (bevacizumab-naive patients) or strata B (patients previously treated with bevacizumab).

Patients will receive oral sorafenib 200 mg twice daily 5 out of 7 days each week and intravenous bevacizumab 5 mg/kg every two weeks.

Tumor biopsies will be obtained from patients before treatment and six weeks into therapy. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fludeoxyglucose 18F-positron emission tomography (FDG-PET) will be obtained from patients before treatment, on day 3 of treatment, and six weeks into therapy.

Patients will be evaluated for response every 8 weeks using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

Approximately 74 patients will be needed to achieve the objectives of the trial.

Study Design

Study Type:
Interventional
Actual Enrollment :
55 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of Sorafenib and Bevacizumab in Epithelial Ovarian, Fallopian, and Peritoneal Cancer
Actual Study Start Date :
Dec 12, 2006
Actual Primary Completion Date :
Jun 26, 2014
Actual Study Completion Date :
Sep 27, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: BAY 43-9006 + Bevacizumab

BAY 43-9006 (sorafenib) + Bevacizumab

Drug: Bevacizumab
bevacizumab 5 mg/kg intravenous (IV) every two weeks
Other Names:
  • Avastin
  • Drug: BAY 43-9006
    BAY 43-9006 200 mg po (by mouth) twice daily 5 out of 7 days each week (Mon-Fri)
    Other Names:
  • sorafenib
  • Outcome Measures

    Primary Outcome Measures

    1. Clinical Response Rate. [patients were followed for a median of 18 weeks (range 1-116 weeks)]

      Clinical response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per the Response Evaluation Criteria in Solid Tumors (RECIST). CR is disappearance of all target lesions. PR is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease (PD) is a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started lasting at least 6 months.

    Secondary Outcome Measures

    1. Progression-free Survival [up to 28 months]

      Progression free survival is defined by the number of weeks between the first day of treatment and the date of cancer progression.

    2. Number of Participants With Adverse Events [up to 28 months]

      Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    • ELIGIBILITY CRITERIA:

    Histopathologically documented recurrent/refractory epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer from a previous biopsy verified by the Laboratory of Pathology, National Cancer Institute (NCI).

    -Recurrent/refractory disease defined as progression within 6 months of upfront platinum-containing therapy or progression after subsequent therapy in previously relapsed patients.

    Disease amenable to percutaneous or skin biopsy as determined by an associate investigator and a member of the interventional team.

    Patient willingness to have biopsies performed.

    Measurable disease defined as tumor greater than or equal to 1 cm.

    Age greater than or equal to 18 years.

    Life expectancy of more than 3 months.

    Performance status of 0 to 1 according to the Eastern Cooperative Oncology Group (ECOG) criteria.

    Adequate organ function as defined below:

    Laboratory Test Required value

    • Leukocytes greater than or equal to 3,000/ microliter

    • Absolute neutrophil count greater than or equal to 1,200/ microliter

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

    • Total bilirubin less than or equal to 1.5 times the institutional upper limits of normal

    • Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) less than or equal to 2.5 times the institutional upper limit of normal

    • Creatinine less than or equal to 1.5 mg/dL

    OR

    • Creatinine clearance greater than or equal to 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.

    • Activated partial thromboplastin time (PTT) less than 1.5 times the institutional upper limits of normal

    • Prothrombin Time (PT)/ International normalized ratio (INR) less than 1.5 times the institutional upper limits of normal

    • Amylase and Lipase Less than institutional upper limits of normal

    Patients must have a urine protein/creatinine ratio (UPC) less than 1.0 for enrollment.

    No surgery, radiation therapy, chemotherapy, immunotherapy, biotherapy, or hormonal therapy (exception raloxifene for bone health) within four weeks (6 weeks for mitomycin C, carboplatin, or nitrosoureas);

    No metabolically active complimentary or alternative therapy for at least 1 week, defined as any ingested or administered chemical substances including herbal medications, but not including acupuncture, hypnosis, meditation, or other non-chemical treatments.

    No monoclonal antibody therapy for at least 6 weeks.

    Patients must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be less than or equal to grade 1 (as defined by Common Terminology Criteria for Adverse Events (CTCAE v3) or returned to baseline. Peripheral neuropathy less than or equal to grade 2 will be allowed as this patient population has universally been treated with platinum-based chemotherapy with residual neuropathy being a common occurrence.

    No other invasive malignancies within the past two years (with the exception of non-melanoma skin cancers, non-invasive bladder cancer, stage I endometrial cancer or cervical cancer synchronous to the ovarian cancer diagnosis and cured by surgical resection).

    Ability to understand and sign an informed consent form.

    Patients who require hematopoietic growth factor support (e.g. epogen, darbepoetin), Non-steroidal anti-inflammatory drugs (NSAIDs), and other maintenance medications prior to study entry will be allowed to continue their supportive therapies.

    Ability to tolerate orally administered medications.

    Contraception is not a consideration as these patients have all had surgical removal of their reproductive organs. Pregnant women are excluded from this study because BAY 43-9006 and bevacizumab 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 BAY 43-9006 and/or bevacizumab, breastfeeding should be discontinued if the mother is treated with BAY 43-9006 and/or bevacizumab.

    There is no limit on the number of prior regimens with which a patient has been treated.

    Patients who have been treated with bevacizumab previously are eligible for the trial if they have progressed while on bevacizumab-based therapy.

    -Disease progression on bevacizumab therapy will be defined as documented increase in disease based on imaging while the patient is receiving bevacizumab or within three months of their last dose of bevacizumab.

    Patients must be at least 6 weeks from their last dose of bevacizumab prior to being enrolled on study.

    Patients who have a healed fistula greater than 28 days prior to enrollment are eligible (refer to section 3.2.15 for patients who have had prior bevacizumab)

    EXCLUSION CRITERIA:

    Serious non-healing wounds (including wounds healing by secondary intention), acute or non-healing ulcers, or bone fractures within 3 months of enrollment.

    Moderate or massive hemoptysis or surgery within 28 days of enrollment.

    Ongoing treatment with any other investigational agents.

    Brain metastases

    • Patients with central nervous system (CNS) metastases within the past 2 years are ineligible. Patients who have had CNS disease curatively treated and without recurrence for 2 years may be eligible. but any CNS disease that has not undergone curative therapy with radiation, gamma knife, and/or surgical therapy are ineligible.

    • CNS imaging will not be mandated for all patients. However, if there is clinical suspicion of CNS involvement, a contrast computed tomography (CT) or magnetic resonance imaging (MRI) of the brain will be required.

    • Patients with CNS metastases may not be on steroids for the purpose of CNS disease or edema control.

    • Patients with CNS disease must be on an anti-seizure medication and that medication cannot be a CYPP4503A modulating agent.

    Thrombotic or embolic events within the past 6 months such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism, unstable angina, or myocardial infarction. Fully treated deep vein thrombosis no longer requiring anticoagulation will be allowed.

    Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (American Heart Association (AHA) Class II or worse), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

    -Patients with evidence of active infection will become eligible for reconsideration 7 days after completing antibiotic therapy.

    Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with sorafenib, bevacizumab, and/or the combination.

    Hypertension defined as systolic blood pressure greater than 150 mmHg or diastolic pressure greater than 90 mmHg despite optimal medical management.

    Therapeutic anticoagulation with coumadin, heparins, or heparinoids.

    Evidence of a bleeding diathesis.

    History of high grade varices or arteriovenous malformations.

    Patients previously treated with sorafenib will not be eligible for this trial.

    Fistula or bowel obstruction or perforation in the 28 days prior to enrollment.

    Patients must not be taking the cytochrome p450 (CYP450) enzyme-inducing drugs phenytoin, carbamazepine, phenobarbital, St. John's wort, or rifampin.

    For patients who have been previously treated with bevacizumab, any severe toxicity associated with bevacizumab while the patient was being treated with the agent will make the patient ineligible for the trial. This includes bevacizumab-induced hypertensive crisis, arterial thromboembolic events (including cardiac ischemia or cerebrovascular ischemia or other arterial thrombosis), nephrotic syndrome, gastrointestinal perforation, serious hemorrhage, and fistulas (unless the fistula completely resolved while the patient was still on bevacizumab or it has been surgically corrected).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda Maryland United States 20892

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Christina M Annunziata, M.D., National Cancer Institute (NCI)

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Christina Annunziata, M.D., Principal Investigator, National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00436215
    Other Study ID Numbers:
    • 070058
    • 07-C-0058
    First Posted:
    Feb 19, 2007
    Last Update Posted:
    Nov 23, 2020
    Last Verified:
    Nov 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Christina Annunziata, M.D., Principal Investigator, National Cancer Institute (NCI)
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title BAY 43-9006 + Bevacizumab
    Arm/Group Description BAY 43-9006 (sorafenib) + Bevacizumab Bevacizumab: bevacizumab 5 mg/kg intravenous (IV) every two weeks BAY 43-9006: BAY 43-9006 200 mg po (by mouth) twice daily 5 out of 7 days each week (Mon-Fri)
    Period Title: Overall Study
    STARTED 55
    COMPLETED 51
    NOT COMPLETED 4

    Baseline Characteristics

    Arm/Group Title BAY 43-9006 + Bevacizumab
    Arm/Group Description BAY 43-9006 (sorafenib) + Bevacizumab Bevacizumab: bevacizumab 5 mg/kg intravenous (IV) every two weeks BAY 43-9006: BAY 43-9006 200 mg po (by mouth) twice daily 5 out of 7 days each week (Mon-Fri)
    Overall Participants 55
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    40
    72.7%
    >=65 years
    15
    27.3%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    56.37
    (12.41)
    Sex: Female, Male (Count of Participants)
    Female
    55
    100%
    Male
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    55
    100%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    3
    5.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    1
    1.8%
    White
    51
    92.7%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (Count of Participants)
    United States
    55
    100%

    Outcome Measures

    1. Primary Outcome
    Title Clinical Response Rate.
    Description Clinical response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per the Response Evaluation Criteria in Solid Tumors (RECIST). CR is disappearance of all target lesions. PR is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease (PD) is a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started lasting at least 6 months.
    Time Frame patients were followed for a median of 18 weeks (range 1-116 weeks)

    Outcome Measure Data

    Analysis Population Description
    Seven patients were not evaluable for response assessment.
    Arm/Group Title BAY 43-9006 + Bevacizumab
    Arm/Group Description BAY 43-9006 (sorafenib) + Bevacizumab Bevacizumab: bevacizumab 5 mg/kg intravenous (IV) every two weeks BAY 43-9006: BAY 43-9006 200 mg po (by mouth) twice daily 5 out of 7 days each week (Mon-Fri)
    Measure Participants 48
    Complete Response
    0
    0%
    Partial Response
    19
    34.5%
    Progressive Disease
    21
    38.2%
    Stable Disease
    60
    109.1%
    2. Secondary Outcome
    Title Progression-free Survival
    Description Progression free survival is defined by the number of weeks between the first day of treatment and the date of cancer progression.
    Time Frame up to 28 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title BAY 43-9006 + Bevacizumab
    Arm/Group Description BAY 43-9006 (sorafenib) + Bevacizumab Bevacizumab: bevacizumab 5 mg/kg intravenous (IV) every two weeks BAY 43-9006: BAY 43-9006 200 mg po (by mouth) twice daily 5 out of 7 days each week (Mon-Fri)
    Measure Participants 55
    Mean (Standard Deviation) [Weeks]
    26
    (24)
    3. Secondary Outcome
    Title Number of Participants With Adverse Events
    Description Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
    Time Frame up to 28 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title BAY 43-9006 + Bevacizumab
    Arm/Group Description BAY 43-9006 (sorafenib) + Bevacizumab Bevacizumab: bevacizumab 5 mg/kg intravenous (IV) every two weeks BAY 43-9006: BAY 43-9006 200 mg po (by mouth) twice daily 5 out of 7 days each week (Mon-Fri)
    Measure Participants 55
    Count of Participants [Participants]
    54
    98.2%

    Adverse Events

    Time Frame up to 28 months
    Adverse Event Reporting Description
    Arm/Group Title BAY 43-9006 + Bevacizumab
    Arm/Group Description BAY 43-9006 (sorafenib) + Bevacizumab Bevacizumab: bevacizumab 5 mg/kg intravenous (IV) every two weeks BAY 43-9006: BAY 43-9006 200 mg po (by mouth) twice daily 5 out of 7 days each week (Mon-Fri)
    All Cause Mortality
    BAY 43-9006 + Bevacizumab
    Affected / at Risk (%) # Events
    Total 1/55 (1.8%)
    Serious Adverse Events
    BAY 43-9006 + Bevacizumab
    Affected / at Risk (%) # Events
    Total 25/55 (45.5%)
    Cardiac disorders
    Pericardial effusion 1/55 (1.8%) 1
    Gastrointestinal disorders
    Abdominal pain 5/55 (9.1%) 5
    Diarrhea 1/55 (1.8%) 1
    Gastrointestinal disorders - Other, specify 1/55 (1.8%) 1
    Nausea 2/55 (3.6%) 2
    Obstruction gastric 1/55 (1.8%) 1
    Small intestinal obstruction 7/55 (12.7%) 7
    Vomiting 1/55 (1.8%) 1
    General disorders
    Fever 2/55 (3.6%) 2
    Hepatobiliary disorders
    Hepatobiliary disorders - Other, specify (bile duct obstruction) 1/55 (1.8%) 1
    Immune system disorders
    Allergic reaction 1/55 (1.8%) 1
    Infections and infestations
    Catheter related infection 1/55 (1.8%) 1
    Cecal infection 1/55 (1.8%) 1
    Wound infection 1/55 (1.8%) 1
    Injury, poisoning and procedural complications
    Vascular access complication 1/55 (1.8%) 1
    Metabolism and nutrition disorders
    Dehydration 1/55 (1.8%) 1
    Hyponatremia 1/55 (1.8%) 1
    Nervous system disorders
    Headache 1/55 (1.8%) 1
    Renal and urinary disorders
    Urinary tract obstruction 1/55 (1.8%) 1
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 2/55 (3.6%) 2
    Pneumonitis 1/55 (1.8%) 1
    Vascular disorders
    Hypertension 1/55 (1.8%) 1
    Thromboembolic event 4/55 (7.3%) 5
    Vascular disorders - Other, specify 1/55 (1.8%) 1
    Other (Not Including Serious) Adverse Events
    BAY 43-9006 + Bevacizumab
    Affected / at Risk (%) # Events
    Total 54/55 (98.2%)
    Blood and lymphatic system disorders
    Anemia 13/55 (23.6%) 21
    Ear and labyrinth disorders
    Middle ear inflammation 1/55 (1.8%) 1
    Vertigo 1/55 (1.8%) 1
    Endocrine disorders
    Hyperthyroidism 9/55 (16.4%) 9
    Hypoparathyroidism 1/55 (1.8%) 1
    Hypothyroidism 4/55 (7.3%) 4
    Eye disorders
    Blurred vision 1/55 (1.8%) 1
    Cataract 1/55 (1.8%) 1
    Dry eye 2/55 (3.6%) 2
    Eye disorders - Other, specify 1/55 (1.8%) 1
    Flashing lights 1/55 (1.8%) 1
    Gastrointestinal disorders
    Abdominal distension 1/55 (1.8%) 1
    Abdominal pain 14/55 (25.5%) 16
    Anal fistula 1/55 (1.8%) 1
    Anal hemorrhage 1/55 (1.8%) 1
    Anal mucositis 1/55 (1.8%) 1
    Anal pain 2/55 (3.6%) 2
    Cheilitis 1/55 (1.8%) 1
    Colitis 1/55 (1.8%) 1
    Constipation 9/55 (16.4%) 9
    Diarrhea 17/55 (30.9%) 35
    Dry mouth 3/55 (5.5%) 3
    Dyspepsia 8/55 (14.5%) 8
    Dysphagia 2/55 (3.6%) 2
    Flatulence 1/55 (1.8%) 1
    Gastroesophageal reflux disease 1/55 (1.8%) 1
    Gastrointestinal disorders - Other, specify (early satiety) 1/55 (1.8%) 1
    Gastrointestinal disorders - Other, specify (gastroenteritis) 1/55 (1.8%) 1
    Gastrointestinal disorders - Other, specify 2/55 (3.6%) 2
    Gingival pain 1/55 (1.8%) 1
    Hemorrhoidal hemorrhage 1/55 (1.8%) 1
    Hemorrhoids 5/55 (9.1%) 5
    Lip pain 1/55 (1.8%) 1
    Lower gastrointestinal hemorrhage 1/55 (1.8%) 1
    Mucositis oral 35/55 (63.6%) 59
    Nausea 18/55 (32.7%) 21
    Oral hemorrhage 1/55 (1.8%) 1
    Oral pain 2/55 (3.6%) 3
    Proctitis 3/55 (5.5%) 4
    Rash maculo-papular 9/55 (16.4%) 10
    Rectal hemorrhage 3/55 (5.5%) 3
    Small intestinal perforation 1/55 (1.8%) 1
    Stomach pain 1/55 (1.8%) 1
    Vomiting 11/55 (20%) 16
    General disorders
    Chills 1/55 (1.8%) 1
    Eye pain 2/55 (3.6%) 2
    Fatigue 26/55 (47.3%) 28
    Fever 6/55 (10.9%) 8
    Flu like symptoms 1/55 (1.8%) 1
    General disorders and administration site conditions - Other, specify 1/55 (1.8%) 1
    Non-cardiac chest pain 1/55 (1.8%) 1
    Pain 6/55 (10.9%) 6
    Immune system disorders
    Allergic reaction 2/55 (3.6%) 2
    Allergic rhinitis 7/55 (12.7%) 8
    Anaphylaxis 1/55 (1.8%) 1
    Infections and infestations
    Anorectal infection 2/55 (3.6%) 2
    Infections and infestations - Other, specify (bronchitis) 1/55 (1.8%) 1
    Infections and infestations - Other, specify (oral candidasis/thrush) 1/55 (1.8%) 1
    Infections and infestations - Other, specify (pyuria) 1/55 (1.8%) 1
    Infections and infestations - Other, specify (unknown ANC) 1/55 (1.8%) 1
    Infections and infestations - Other, specify 1/55 (1.8%) 1
    Infections and infestations - Other, specify 3/55 (5.5%) 3
    Mucosal infection 1/55 (1.8%) 1
    Pharyngitis 1/55 (1.8%) 1
    Phlebitis infective 1/55 (1.8%) 1
    Rhinitis infective 1/55 (1.8%) 1
    Sinusitis 2/55 (3.6%) 2
    Skin infection 4/55 (7.3%) 4
    Tooth infection 1/55 (1.8%) 1
    Upper respiratory infection 11/55 (20%) 12
    Urinary tract infection 8/55 (14.5%) 9
    Vaginal infection 3/55 (5.5%) 3
    Injury, poisoning and procedural complications
    Bruising 1/55 (1.8%) 1
    Burn 1/55 (1.8%) 1
    Investigations
    Activated partial thromboplastin time prolonged 20/55 (36.4%) 38
    Alanine aminotransferase increased 30/55 (54.5%) 58
    Alkaline phosphatase increased 23/55 (41.8%) 46
    Aspartate aminotransferase increased 38/55 (69.1%) 65
    Blood bilirubin increased 10/55 (18.2%) 14
    CPK increased 3/55 (5.5%) 4
    Creatinine increased 10/55 (18.2%) 22
    Investigations - Other, specify 2/55 (3.6%) 2
    Lipase increased 6/55 (10.9%) 13
    Lymphocyte count decreased 26/55 (47.3%) 69
    Neutrophil count decreased 3/55 (5.5%) 4
    Platelet count decreased 19/55 (34.5%) 27
    Serum amylase increased 6/55 (10.9%) 12
    Weight gain 2/55 (3.6%) 3
    Weight loss 29/55 (52.7%) 44
    White blood cell decreased 10/55 (18.2%) 15
    Metabolism and nutrition disorders
    Anorexia 17/55 (30.9%) 22
    Dehydration 5/55 (9.1%) 5
    Hypercalcemia 11/55 (20%) 17
    Hyperglycemia 5/55 (9.1%) 5
    Hyperkalemia 6/55 (10.9%) 7
    Hypermagnesemia 12/55 (21.8%) 15
    Hyperuricemia 7/55 (12.7%) 10
    Hypoalbuminemia 41/55 (74.5%) 85
    Hypocalcemia 3/55 (5.5%) 4
    Hypoglycemia 1/55 (1.8%) 1
    Hypokalemia 6/55 (10.9%) 8
    Hypomagnesemia 23/55 (41.8%) 50
    Hyponatremia 31/55 (56.4%) 75
    Hypophosphatemia 11/55 (20%) 15
    Musculoskeletal and connective tissue disorders
    Arthralgia 3/55 (5.5%) 3
    Arthritis 1/55 (1.8%) 1
    Back pain 9/55 (16.4%) 10
    Bone pain 1/55 (1.8%) 1
    Chest wall pain 3/55 (5.5%) 4
    Musculoskeletal and connective tissue disorder - Other, specify (cramps) 1/55 (1.8%) 1
    Musculoskeletal and connective tissue disorder - Other, specify (muscle cramping) 1/55 (1.8%) 1
    Musculoskeletal and connective tissue disorder - Other, specify 1/55 (1.8%) 1
    Musculoskeletal and connective tissue disorder - Other, specify 2/55 (3.6%) 2
    Myalgia 8/55 (14.5%) 8
    Neck pain 2/55 (3.6%) 2
    Pain in extremity 9/55 (16.4%) 11
    Nervous system disorders
    Dizziness 6/55 (10.9%) 6
    Dysgeusia 10/55 (18.2%) 10
    Headache 22/55 (40%) 30
    Lethargy 1/55 (1.8%) 1
    Memory impairment 1/55 (1.8%) 1
    Nervous system disorders - Other, specify 2/55 (3.6%) 2
    Paresthesia 1/55 (1.8%) 3
    Peripheral sensory neuropathy 4/55 (7.3%) 5
    Psychiatric disorders
    Agitation 1/55 (1.8%) 1
    Anxiety 3/55 (5.5%) 3
    Depression 4/55 (7.3%) 5
    Insomnia 6/55 (10.9%) 6
    Renal and urinary disorders
    Hematuria 1/55 (1.8%) 1
    Hemoglobinuria 3/55 (5.5%) 4
    Proteinuria 13/55 (23.6%) 18
    Rectal pain 1/55 (1.8%) 1
    Renal and urinary disorders - Other, specify (dysuria) 1/55 (1.8%) 1
    Renal and urinary disorders - Other, specify (high blood urea nitrogen) 1/55 (1.8%) 1
    Renal and urinary disorders - Other, specify (WBC in urine) 1/55 (1.8%) 1
    Renal and urinary disorders - Other, specify 1/55 (1.8%) 1
    Renal hemorrhage 1/55 (1.8%) 2
    Urinary frequency 3/55 (5.5%) 3
    Reproductive system and breast disorders
    Pelvic pain 2/55 (3.6%) 2
    Vaginal discharge 2/55 (3.6%) 2
    Vaginal hemorrhage 3/55 (5.5%) 3
    Vaginal inflammation 1/55 (1.8%) 1
    Respiratory, thoracic and mediastinal disorders
    Cough 5/55 (9.1%) 5
    Dyspnea 5/55 (9.1%) 5
    Epistaxis 18/55 (32.7%) 19
    Hoarseness 10/55 (18.2%) 10
    Nasal congestion 1/55 (1.8%) 1
    Pharyngeal mucositis 1/55 (1.8%) 1
    Pharyngolaryngeal pain 1/55 (1.8%) 1
    Pleural effusion 1/55 (1.8%) 2
    Pleuritic pain 2/55 (3.6%) 3
    Postnasal drip 3/55 (5.5%) 3
    Sinus disorder 13/55 (23.6%) 13
    Sore throat 3/55 (5.5%) 3
    Voice alteration 13/55 (23.6%) 13
    Skin and subcutaneous tissue disorders
    Alopecia 6/55 (10.9%) 6
    Dry skin 4/55 (7.3%) 4
    Hyperhidrosis 1/55 (1.8%) 1
    Nail discoloration 2/55 (3.6%) 2
    Nail loss 3/55 (5.5%) 3
    Pain of skin 1/55 (1.8%) 1
    Palmar-plantar erythrodysesthesia syndrome 47/55 (85.5%) 104
    Pruritus 8/55 (14.5%) 11
    Rash acneiform 12/55 (21.8%) 15
    Scalp pain 2/55 (3.6%) 3
    Skin and subcutaneous tissue disorders - Other, specify 1/55 (1.8%) 1
    Skin and subcutaneous tissue disorders - Other, specify 2/55 (3.6%) 2
    Skin and subcutaneous tissue disorders - Other, specify 1/55 (1.8%) 1
    Skin and subcutaneous tissue disorders - Other, specify 1/55 (1.8%) 1
    Skin and subcutaneous tissue disorders - Other, specify 2/55 (3.6%) 2
    Urticaria 1/55 (1.8%) 1
    Vascular disorders
    Flushing 1/55 (1.8%) 1
    Hot flashes 1/55 (1.8%) 1
    Hypertension 30/55 (54.5%) 49
    Hypotension 2/55 (3.6%) 2

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Christina Annunziata
    Organization National Cancer Institute
    Phone 301-402-7189
    Email annunzic@mail.nih.gov
    Responsible Party:
    Christina Annunziata, M.D., Principal Investigator, National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00436215
    Other Study ID Numbers:
    • 070058
    • 07-C-0058
    First Posted:
    Feb 19, 2007
    Last Update Posted:
    Nov 23, 2020
    Last Verified:
    Nov 1, 2020