Oral Pazopanib Plus Oral Topotecan Metronomic Antiangiogenic Therapy for Recurrent Glioblastoma Multiforme (A) Without Prior Bevacizumab Exposure and (B) After Failing Prior Bevacizumab

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT01931098
Collaborator
(none)
35
1
2
45.1
0.8

Study Details

Study Description

Brief Summary

Background:

Glioblastoma is the most common and most aggressive type of malignant brain tumor. The drug pazopanib is used to treat people with a type of kidney cancer. Topotecan is used to treat lung cancer. Both topotecan and pazopanib have individually been used to treat patients with glioblastoma and some anti-tumor activity has been found. Researchers want to see if these two drugs together may be able to help people with glioblastoma.

Objectives:

To learn if pazopanib with topotecan can help control glioblastoma. Also, to study the safety of this drug combination.

Eligibility:

Adults at least 18 years old whose glioblastoma has returned after treatment.

Design:
Participants will be screened with:

Medical history

Physical exam

Blood and urine tests

Brain computed tomography (CT) or magnetic resonance imaging (MRI) For these, participants lay in a machine that takes pictures.

Chest CT scan or x-ray

Heart electrocardiogram (EKG)

A questionnaire about quality of life

Participants will be assigned to a study group.

Participants will take the study drugs for 28-day cycles for up to 1 year. They will take capsules of topotecan by mouth once every day. They will take tablets of pazopanib by mouth once every day.

Participants will write in a diary the times they take the study drugs.

Participants will have several study visits during each cycle. These may include

Blood pressure measurement

Blood and urine tests

EKG

Physical exam and/or neurological exam

Brain MRI or CT scan to check the status of the disease

A symptom questionnaire

At the end of treatment, participants will have a physical exam. They may have blood drawn.

Participants will have follow-up calls once every 3 months to check.

Detailed Description

Background

  • Glioblastoma (GBM) is the most common primary brain tumor. With optimal treatment,consisting of focal radiotherapy with concurrent chemotherapy, followed by adjuvant chemotherapy, median survival is 14.6 months. Most patients have evidence of tumor progression within one year of diagnosis despite treatment. At progression, treatment options are limited and mostly ineffective.

  • Recently, bevacizumab was approved for recurrent GBM patients who fail bevacizumab indicate a short survival, on the order of 10 weeks, an approximate PFS 3 and 6 months of 0%.

  • Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor (VEGFR), Platelet-derived growth factor receptors (PDGFR), and c-Kit, and was recently Food and Drug Administration (FDA) approved for advanced renal cell carcinoma.

  • Topotecan is an orally bioavailable topoisomerase I and Hypoxia-inducible factor 1 (HIF-1) alpha inhibitor with reasonably high central nervous system (CNS)/cerebrospinal fluid (CSF) penetration

  • Recent pre-clinical reports have begun to argue for the clinical testing of metronomic chemotherapy administration in various cancers. The theory of improved activity of Pazopanib + Topotecan administered metronomically is based on targeting tumor vasculature (both existing capillary endothelial cells and circulating bone marrow derived endothelial cell precursors), immune modulation, as well as tumor cell HIF-1 alpha inhibition, and the induction of Deoxyribonucleic acid (DNA) damage. Further support for the combination comes from recent data tying drug-induced VEGF inhibition to the induction of HIF-1 alpha activity in GBM suggesting possible synergy between Pazopanib and Topotecan

  • The combination of Topotecan and Pazopanib has been directly demonstrated as active in

animal models

Objectives

  • 6 month progression free survival rate for recurrent glioblastoma (rGBM) patients with no prior bevacizumab exposure treated with pazopanib and topotecan (Group A).

  • 3 month progression free survival rate for rGBM patients with prior bevacizumab exposure treated with pazopanib and topotecan (Group B).

Eligibility

  • Histologically proven intracranial glioblastoma multiforme (GBM) or gliosarcoma (GS) with evidence of progression on MRI or CT scan.

  • Patient must have failed prior chemoradiation with temozolomide and any other therapies except Bevacizumab (BEV) (group A), or must have failed primary chemoradiation and a BEVincorporating treatment (group B).

  • Patients must be greater than 12 weeks following completion of chemoradiation.

  • Archived tumor tissue must be available for confirmation of the diagnosis

  • Patients must be > 18 years old.

  • Patients must have a Karnofsky performance status of > 60.

  • Patients must have adequate organ function.

  • No pregnancy or lactation.

  • Patients must not have any significant medical illnesses that in the investigators opinion cannot be adequately controlled with appropriate therapy or would compromise the patients ability to tolerate this therapy.

  • No history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are eligible.

  • No clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, or the absorption of the medications.

  • No prior major surgery or trauma within 28 days and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).

  • No evidence of active bleeding or bleeding diathesis.

  • No known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.

  • No serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subjects safety, provision of informed consent, or compliance to study procedures.

  • No ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity, except alopecia.

  • No ongoing use of enzyme-inducing anti-epileptic agents (EIAEDs), unless 2 week washout has elapsed form last dose of EIAED.

  • No known hypersensitivity to pazopanib or topotecan or to their excipients.

  • No total daily dose of dexamethasone greater than 16 mg/day.

  • No prior therapy with topotecan, pazopanib, or related drugs such as tyrosine kinase inhibitors, VEGF inhibitors (except bevacizumab). Prior treatment with Tyrosine kinase inhibitors (TKIs) that do not impact VEGFR -1, -2, or -3, Platelet Derived Growth Factor Receptor Alpha (PDGFRa) Platelet Derived Growth Factor Receptor Beta (-b) of cKIT could be allowed.

Design

This is a 2 arm phase II trial of the combination of topotecan and pazopanib in patients with recurrent GBM or GS. Patients will be enrolled into one of the following groups: (A) Glioblastoma or gliosarcoma with no prior bevacizumab exposure: (B) Glioblastoma or

gliosarcoma with prior bevacizumab exposure. Topotecan and pazopanib are administered orally daily. The primary efficacy endpoint is progression free survival (PFS) at six months from patient registration for bevacizumab na(SqrRoot) ve patients and progression free survival (PFS) at 3 months for patients with prior bevacizumab treatment.

Study Design

Study Type:
Interventional
Actual Enrollment :
35 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Trial of Oral Pazopanib Plus Oral Topotecan Metronomic Antiangiogenic Therapy for Recurrent Glioblastoma Multiforme (A)Without Prior Bevacizumab Exposure and (B) After Failing Prior Bevacizumab
Actual Study Start Date :
Dec 10, 2015
Actual Primary Completion Date :
Sep 12, 2019
Actual Study Completion Date :
Sep 12, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure

Topotecan .25 mg and pazopanib 600 mg are administered orally daily until progression, up to one year.

Drug: topotecan
Taken .25 mg orally, daily continuous until progression up to one year.
Other Names:
  • Hycamtin
  • Drug: pazopanib
    600 mg orally, daily until progression, up to one year.
    Other Names:
  • Votrient
  • Experimental: Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure

    Topotecan .25 mg and pazopanib 600 mg are administered orally daily until progression, up to one year.

    Drug: topotecan
    Taken .25 mg orally, daily continuous until progression up to one year.
    Other Names:
  • Hycamtin
  • Drug: pazopanib
    600 mg orally, daily until progression, up to one year.
    Other Names:
  • Votrient
  • Outcome Measures

    Primary Outcome Measures

    1. Proportion of Patients That Have Progressive Survival (PFS) at Six Months From Patient Registration for Bevacizumab Naive Patients and PFS at 3 Months for Patients With Prior Bevacizumab Treatment [six months from patient registration for bevacizumab naive patients, and 3 months from patient registration for patients with prior bevacizumab treatment]

      PFS was evaluated using the Kaplan-Meier product-limit survival curve methodology. For participants with no prior bevacizumab exposure, PFS is defined as 2 or more participants who are progression free at 6 months. For participants with prior bevacizumab exposure, PFS is defined as 1 or more participants who are progression free at 3 months. Progression is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) or clear worsening of evaluable disease or the appearance of any new lesions.

    Secondary Outcome Measures

    1. Overall Survival [From date of registration to date of death due to any cause, up to 5 years.]

      OS was evaluated using the Kaplan-Meier product-limit survival curve methodology and is defined as the time from date of registration to date of death due to any cause.

    2. Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle [Baseline, and Cycles 1-6]

      Responders and Non-Responders symptom presence and severity were assessed by the M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) questionnaire using an scale of (0-10); 0 being not present and 10 being the worst, and Responders were defined as patients with stable disease (SD) and partial response (PR) as their best response, and Non-responders were defined as patients with disease progression (PD) as their best response. Partial response is greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesion. Progressive disease is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease). And stable disease does not qualify for complete response, partial response or progression.

    3. Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle [Baseline, and Cycles 1-6]

      Responders and Non-Responders symptom interference was assessed by the M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) questionnaire that determined how much general activity, mood, work inside and outside the home, relations with other people, walking and enjoying life interfered with a participant's life rated on an scale (0-10); 0 being not present and 10 being the worst. Responders were defined as patients with stable disease (SD) and partial response (PR) as their best response, and Non-responders were defined as patients with disease progression (PD) as their best response. Partial response is greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesion. Progressive disease is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease). And stable disease does not qualify for complete response, partial response or progression.

    4. Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) [Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.]

      Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    • General Inclusion Criteria

    • Patients with histologically proven intracranial glioblastoma multiforme (GBM) or gliosarcoma (GS). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a GBM or GS is made. Patients must have evidence of progression of the GBM or GS on magnetic resonance imaging (MRI) or computed tomography (CT) scan. Patient must have failed prior chemoradiation with temozolomide and any other therapies except BEV (group A), or must have failed primary chemoradiation and a BEV-incorporating treatment (group B).

    • Patients may have had treatment for no more than 2 prior relapses. Relapse is defined as progression following initial therapy (i.e. radiation+/- chemo if that was used as initial therapy). The intent therefore is that patients had no more than 3 prior therapies

    (initial and treatment for 2 relapses). If the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse.

    For patients who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse.

    • Patients must be greater than 12 weeks following completion of chemoradiation or any additional radiation to reduce the chance of pseudoprogression.

    • Measurable disease is required unless patient is post-operative and in that case patient can have no evidence of disease.

    • All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.

    • Archived tumor tissue must be available for all subjects for confirmation of the diagnosis before or during treatment. Samples must be provided within 4 weeks of enrollment.

    • Patients must be greater than or equal to 18 years old.

    • Patients must have a Karnofsky performance status of greater than or equal to 60.

    • At the time of registration: Patients must have recovered from the toxic effects of prior therapy: greater than or equal to 28 days from any investigational agent, greater than or equal to 28 days from prior cytotoxic therapy, greater than or equal to 14 days from vincristine, greater than or equal to 42 days from nitrosoureas, greater than or equal to 21 days from procarbazine administration, >21 days from bevacizumab administration and greater than or equal to 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of noncytotoxic agents should be directed to Academic Principal Investigator (PI).

    • Patients must have adequate organ function:

    • Bone marrow function (White blood cell (WBC) greater than or equal to 3,000/microl, absolute neutrophil count (ANC) greater than or equal to 1,500/mm3, platelet count of greater than or equal to 100,000/mm3, and hemoglobin greater than or equal to 10 gm/dl).

    ---Eligibility level for hemoglobin may be reached by transfusion.

    • Liver function (alanine amino transferase (ALT) and aspartate aminotransferase (AST) < 2.5 X upper limit of normal (ULN), and total bilirubin < 1.5 X ULN), prothrombin time (PT) or international normalized ratio (INR), and activated partial thromboplastin time (aPTT) less than or equal to 1.2 X ULN.

    • Concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN (upper limit of normal) are not permitted.

    • Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation.

    • Renal function (creatinine less than or equal to 1.5 mg/dL (133 micromol/L), or if > 1.5 mg/dL, calculated creatinine clearance greater than or equal to 50 cc/min), and urine protein to creatinine ratio of < 1 prior to registration.

    • Patients must have shown unequivocal radiographic evidence for tumor progression by MRI or CT scan as defined by Section 6.4.1.4.5. A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable or decreasing for at least 5 days. If the steroid dose is increased between the date of imaging and registration a new baseline MR/CT is required. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement.

    • Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:

    --They have recovered from the effects of surgery and be > 28 days from surgery.

    • Residual disease following resection of recurrent GBM or GS is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a CT/ MRI should be done no later than 96 hours in the immediate post-operative period or at least 4 weeks post-operatively, within 14 days prior to registration. If the 96-hour scan is more than 14 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.

    • Patients must have failed prior radiation therapy and must have an interval of greater than or equal to 12 weeks from the completion of radiation therapy to study entry.

    • Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either positron emission tomography (PET) or Thallium scanning, MR spectroscopy or surgical/pathological documentation of disease.

    • A female is eligible to enter and participate in this study if she is of:

    • Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had:

    • A hysterectomy

    • A bilateral oophorectomy (ovariectomy)

    • A bilateral tubal ligation

    • Is post-menopausal

    • Subjects not using hormone replacement therapy (HRT) must have experienced in questionable cases, have a follicle stimulating hormone (FSH) value >40 mIU/mL and an estradiol value < 40pg/mL (<140 pmol/L).

    • Subjects using HRT must have experienced total cessation of menses for >= 1year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT

    • Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception. Novartis acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:

    • Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product. Oral contraceptive, either combined or progestogen alone.

    • Injectable progestogen.

    • Implants of levonorgestrel.

    • Estrogenic vaginal ring.

    • Percutaneous contraceptive patches.

    • Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year.

    • Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject.

    • Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository).

    • Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.

    General Exclusion Criteria

    • Patients must not have any significant medical illnesses that in the investigators opinion cannot be adequately controlled with appropriate therapy or would compromise the patients ability to tolerate this therapy.

    • Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.

    • Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:

    • Active peptic ulcer disease.

    • Known intraluminal metastatic lesion/s with risk of bleeding.

    • Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation.

    • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment.

    • Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:

    • Malabsorption syndrome

    • Major resection of the stomach or small bowel.

    • Presence of uncontrolled infection.

    • Corrected QT interval (QTc) > 480 msecs using Bazett's formula. Bazett's Formula: QTc (Bazett)=QT/RR

    • History of any one or more of the following cardiovascular conditions within the past 6 months:

    • Cardiac angioplasty or stenting

    • Myocardial infarction

    • Unstable angina

    • Coronary artery bypass graft surgery

    • Symptomatic peripheral vascular disease

    • Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA), see appendix 13.7

    • Poorly controlled hypertension [defined as systolic blood pressure (SBP) of greater than or equal to 140 mmHg or diastolic blood pressure (DBP) of less than or equal to 90mmHg]. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP/DBP values from each BP assessment must be less than or equal to 140/90 mmHg in order for a subject to be eligible for the study.

    • History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anticoagulating

    agents for at least 6 weeks are eligible.

    • Prior major surgery or trauma within 28 days and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).

    • Evidence of active bleeding or bleeding diathesis.

    • Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

    • Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of study drug.

    • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subjects safety, provision of informed consent, or compliance to study procedures.

    • Unable or unwilling to discontinue use of inducers and inhibitors of Cytochrome P450 (CYP450) listed in Appendix 13.4 and breast cancer resistance protein (BCRP) and P-glycoprotein (PgP) inducers and inhibitors for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study. (CYP3A4 substrates can be administered, but investigators will need to be aware of possible increased or decreased effectiveness of the non-study drug and this should be recorded in concomitant medications. Dexamethasone is acceptable although listed as a CYP3A4 inducers/inhibitors as long as the dose is 16 mg/day or lesser.

    • Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity, except alopecia.

    • Ongoing use of enzyme-inducing anti-epileptic agents (EIAEDs), unless 2 week washout has elapsed form last dose of EIAED.

    • Patients must not have any significant medical illnesses that in the investigators opinion cannot be adequately controlled with appropriate therapy or would compromise the patients ability to tolerate this therapy.

    • Patients with a known hypersensitivity to pazopanib or topotecan or to their excipients.

    • Patients on total daily dose of dexamethasone greater than 16 mg/day.

    • Patients must not have received prior therapy with topotecan, pazopanib, or related drugs such as tyrosine kinase inhibitors, VEGF inhibitors (except bevacizumab). Prior treatment with TKIs that do not impact VEGFR -1, -2, or -3, Platelet Derived Growth Factor Receptor Alpha (PDGFRa) Platelet Derived Growth Factor Receptor Beta (-b) of cKIT could be allowed.

    • Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.

    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: Mark R Gilbert, M.D., National Cancer Institute (NCI)

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Mark Gilbert, M.D., Principal Investigator, National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01931098
    Other Study ID Numbers:
    • 160034
    • 16-C-0034
    First Posted:
    Aug 29, 2013
    Last Update Posted:
    Nov 24, 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
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Mark Gilbert, M.D., Principal Investigator, National Cancer Institute (NCI)
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure
    Arm/Group Description Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year. Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.
    Period Title: Overall Study
    STARTED 9 26
    COMPLETED 9 22
    NOT COMPLETED 0 4

    Baseline Characteristics

    Arm/Group Title Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure Total
    Arm/Group Description Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year. Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year. Total of all reporting groups
    Overall Participants 9 26 35
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    7
    77.8%
    22
    84.6%
    29
    82.9%
    >=65 years
    2
    22.2%
    4
    15.4%
    6
    17.1%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    54.6
    (9.51)
    50.81
    (13.26)
    51.79
    (12.38)
    Sex: Female, Male (Count of Participants)
    Female
    5
    55.6%
    11
    42.3%
    16
    45.7%
    Male
    4
    44.4%
    15
    57.7%
    19
    54.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    9
    100%
    26
    100%
    35
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    11.1%
    0
    0%
    1
    2.9%
    White
    8
    88.9%
    26
    100%
    34
    97.1%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    9
    100%
    26
    100%
    35
    100%

    Outcome Measures

    1. Primary Outcome
    Title Proportion of Patients That Have Progressive Survival (PFS) at Six Months From Patient Registration for Bevacizumab Naive Patients and PFS at 3 Months for Patients With Prior Bevacizumab Treatment
    Description PFS was evaluated using the Kaplan-Meier product-limit survival curve methodology. For participants with no prior bevacizumab exposure, PFS is defined as 2 or more participants who are progression free at 6 months. For participants with prior bevacizumab exposure, PFS is defined as 1 or more participants who are progression free at 3 months. Progression is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) or clear worsening of evaluable disease or the appearance of any new lesions.
    Time Frame six months from patient registration for bevacizumab naive patients, and 3 months from patient registration for patients with prior bevacizumab treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure
    Arm/Group Description Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year. Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.
    Measure Participants 9 26
    3 months
    0.44
    4.9%
    0.18
    0.7%
    6 months
    0.11
    1.2%
    0
    0%
    2. Secondary Outcome
    Title Overall Survival
    Description OS was evaluated using the Kaplan-Meier product-limit survival curve methodology and is defined as the time from date of registration to date of death due to any cause.
    Time Frame From date of registration to date of death due to any cause, up to 5 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure
    Arm/Group Description Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year. Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.
    Measure Participants 9 26
    Median (95% Confidence Interval) [Months]
    7.1
    6.3
    3. Secondary Outcome
    Title Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle
    Description Responders and Non-Responders symptom presence and severity were assessed by the M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) questionnaire using an scale of (0-10); 0 being not present and 10 being the worst, and Responders were defined as patients with stable disease (SD) and partial response (PR) as their best response, and Non-responders were defined as patients with disease progression (PD) as their best response. Partial response is greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesion. Progressive disease is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease). And stable disease does not qualify for complete response, partial response or progression.
    Time Frame Baseline, and Cycles 1-6

    Outcome Measure Data

    Analysis Population Description
    One participant in the second Arm/Group did not have a best response recorded and was excluded from questions involving responders and non-responders.
    Arm/Group Title Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure
    Arm/Group Description Participants received imaging and corresponding MDSAI-BT at baseline and even-numbered cycles. Participants received imaging and corresponding MDSAI-BT at baseline and cycle 1 thru cycle 3, and subsequent odd-numbered cycles.
    Measure Participants 9 25
    Responders - baseline
    1.1
    (0.4)
    1.9
    (1.3)
    Responders - Cycle 1
    2.3
    (1.4)
    Responders - Cycle 2
    0.8
    (0.4)
    3.5
    (2.5)
    Responders - Cycle 3
    2.9
    (3.4)
    Responders - Cycle 4
    2.0
    (1.7)
    Responders - Cycle 5
    1.5
    Responders - Cycle 6
    2.1
    (2.0)
    Non-Responders - baseline
    1.6
    (0.7)
    2.8
    (2.1)
    Non-Responders - Cycle 1
    3.0
    (1.9)
    Non-Responders - Cycle 2
    3.0
    Overall Responders and Non-Responders - baseline
    1.3
    (0.5)
    2.4
    (1.7)
    Overall Responders and Non-Responders - Cycle 1
    2.5
    (1.5)
    Overall Responders and Non-Responders - Cycle 2
    1.4
    (1.2)
    3.5
    (2.5)
    Overall Responders and Non-Responders - Cycle 3
    2.9
    (3.4)
    Overall Responders and Non-Responders - Cycle 4
    2.0
    (1.7)
    1.5
    Overall Responders and Non-Responders - Cycle 6
    2.1
    (2.0)
    4. Secondary Outcome
    Title Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle
    Description Responders and Non-Responders symptom interference was assessed by the M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) questionnaire that determined how much general activity, mood, work inside and outside the home, relations with other people, walking and enjoying life interfered with a participant's life rated on an scale (0-10); 0 being not present and 10 being the worst. Responders were defined as patients with stable disease (SD) and partial response (PR) as their best response, and Non-responders were defined as patients with disease progression (PD) as their best response. Partial response is greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesion. Progressive disease is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease). And stable disease does not qualify for complete response, partial response or progression.
    Time Frame Baseline, and Cycles 1-6

    Outcome Measure Data

    Analysis Population Description
    One participant in the second Arm/Group did not have a best response recorded and was excluded from questions involving responders and non-responders.
    Arm/Group Title Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure
    Arm/Group Description Participants received imaging and corresponding MDSAI-BT at baseline and even-numbered cycles. Participants received imaging and corresponding MDSAI-BT at baseline and cycle 1 thru cycle 3, and subsequent odd-numbered cycles.
    Measure Participants 9 25
    Responders - baseline
    2.1
    (1.2)
    3.6
    (2.9)
    Responders - Cycle 1
    3.7
    (2.5)
    Responders - Cycle 2
    1.4
    (0.4)
    6.0
    (3.2)
    Responders - Cycle 3
    4.2
    (4.0)
    Responders - Cycle 4
    3.2
    (2.0)
    Responders - Cycle 5
    0.2
    Responders - Cycle 6
    2.7
    (0.9)
    Non-Responders - baseline
    1.7
    (1.2)
    3.9
    (3.2)
    Non-Responders - Cycle 1
    4.8
    (3.8)
    Non-Responders - Cycle 2
    3.0
    Overall Responders and Non-Responders - baseline
    2.0
    (1.2)
    3.8
    (2.9)
    Overall Responders and Non-Responders - Cycle 1
    4.0
    (2.9)
    Overall Responders and Non-Responders - Cycle 2
    1.8
    (0.9)
    6.0
    (3.2)
    Overall Responders and Non-Responders - Cycle 3
    4.2
    (4.0)
    Overall Responders and Non-Responders - Cycle 4
    3.2
    (2.0)
    Overall Responders and Non-Responders - Cycle 5
    0.2
    Overall Responders and Non-Responders - Cycle 6
    2.7
    (0.9)
    5. Secondary Outcome
    Title Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
    Description Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
    Time Frame Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure
    Arm/Group Description Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year. Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.
    Measure Participants 9 26
    Count of Participants [Participants]
    9
    100%
    21
    80.8%

    Adverse Events

    Time Frame Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.
    Adverse Event Reporting Description
    Arm/Group Title Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure
    Arm/Group Description Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year. Topotecan and pazopanib are administered orally daily. topotecan: Taken .25 mg orally, daily continuous until progression up to one year. pazopanib: 600 mg orally, daily until progression, up to one year.
    All Cause Mortality
    Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/9 (100%) 20/26 (76.9%)
    Serious Adverse Events
    Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/9 (22.2%) 7/26 (26.9%)
    Gastrointestinal disorders
    Upper gastrointestinal hemorrhage 0/9 (0%) 0 1/26 (3.8%) 1
    Hepatobiliary disorders
    Cholecystitis 0/9 (0%) 0 1/26 (3.8%) 1
    Infections and infestations
    Meningitis 1/9 (11.1%) 1 1/26 (3.8%) 1
    Investigations
    Alanine aminotransferase increased 0/9 (0%) 0 1/26 (3.8%) 1
    Metabolism and nutrition disorders
    Hyperglycemia 0/9 (0%) 0 1/26 (3.8%) 1
    Musculoskeletal and connective tissue disorders
    Generalized muscle weakness 0/9 (0%) 0 1/26 (3.8%) 1
    Muscle weakness left-sided 2/9 (22.2%) 3 1/26 (3.8%) 1
    Musculoskeletal and connective tissue disorder - Other, specify 1/9 (11.1%) 1 0/26 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Glioblastoma 0/9 (0%) 0 2/26 (7.7%) 2
    Nervous system disorders
    Headache 1/9 (11.1%) 1 0/26 (0%) 0
    Seizure 1/9 (11.1%) 1 1/26 (3.8%) 1
    Vascular disorders
    Thromboembolic event 0/9 (0%) 0 1/26 (3.8%) 1
    Other (Not Including Serious) Adverse Events
    Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/9 (100%) 21/26 (80.8%)
    Blood and lymphatic system disorders
    Anemia 1/9 (11.1%) 1 2/26 (7.7%) 2
    Blood and lymphatic system disorders - Other, Blood in stool 0/9 (0%) 0 1/26 (3.8%) 1
    Blood and lymphatic system disorders - Other, Elevated ALT 0/9 (0%) 0 1/26 (3.8%) 2
    Blood and lymphatic system disorders - Other, Elevated AST 0/9 (0%) 0 1/26 (3.8%) 2
    Cardiac disorders
    Sinus tachycardia 1/9 (11.1%) 1 0/26 (0%) 0
    Endocrine disorders
    Hyperthyroidism 0/9 (0%) 0 1/26 (3.8%) 1
    Hypothyroidism 0/9 (0%) 0 1/26 (3.8%) 1
    Eye disorders
    Blurred vision 0/9 (0%) 0 3/26 (11.5%) 3
    Dry eye 0/9 (0%) 0 1/26 (3.8%) 1
    Eye disorders - Other, Right Hemianops 1/9 (11.1%) 1 0/26 (0%) 0
    Eye disorders - Other, Left upper quadrant defect 1/9 (11.1%) 1 0/26 (0%) 0
    Eye disorders - Other, specify 0/9 (0%) 0 1/26 (3.8%) 1
    Gastrointestinal disorders
    Abdominal pain 0/9 (0%) 0 2/26 (7.7%) 3
    Constipation 0/9 (0%) 0 4/26 (15.4%) 4
    Diarrhea 4/9 (44.4%) 4 8/26 (30.8%) 9
    Dry mouth 1/9 (11.1%) 1 0/26 (0%) 0
    Dyspepsia 0/9 (0%) 0 1/26 (3.8%) 1
    Dysphagia 1/9 (11.1%) 1 0/26 (0%) 0
    Gastroesophageal reflux disease 1/9 (11.1%) 1 1/26 (3.8%) 1
    Gastrointestinal disorders - Other, specify 1/9 (11.1%) 1 0/26 (0%) 0
    Gastrointestinal disorders - Other, Intermittent blood in stool (Hematochezia) 0/9 (0%) 0 1/26 (3.8%) 1
    Gastrointestinal disorders - Other, Mouth sores 0/9 (0%) 0 1/26 (3.8%) 1
    Gastrointestinal disorders - Other, Sphincter Dysfunction 0/9 (0%) 0 1/26 (3.8%) 1
    Nausea 3/9 (33.3%) 3 8/26 (30.8%) 11
    Oral pain 1/9 (11.1%) 1 0/26 (0%) 0
    Vomiting 3/9 (33.3%) 3 6/26 (23.1%) 8
    General disorders
    Fatigue 6/9 (66.7%) 6 12/26 (46.2%) 13
    Flu like symptoms 1/9 (11.1%) 1 0/26 (0%) 0
    Gait disturbance 2/9 (22.2%) 2 2/26 (7.7%) 2
    Pain 2/9 (22.2%) 2 1/26 (3.8%) 1
    Infections and infestations
    Bladder infection 0/9 (0%) 0 1/26 (3.8%) 1
    Bronchial infection 0/9 (0%) 0 2/26 (7.7%) 2
    Sinusitis 1/9 (11.1%) 1 1/26 (3.8%) 1
    Wound infection 0/9 (0%) 0 1/26 (3.8%) 1
    Injury, poisoning and procedural complications
    Bruising 1/9 (11.1%) 1 0/26 (0%) 0
    Fall 1/9 (11.1%) 1 1/26 (3.8%) 1
    Investigations
    Alanine aminotransferase increased 1/9 (11.1%) 2 2/26 (7.7%) 2
    Aspartate aminotransferase increased 1/9 (11.1%) 2 1/26 (3.8%) 1
    Blood bilirubin increased 0/9 (0%) 0 1/26 (3.8%) 1
    Investigations - Other, Abnormal taste 0/9 (0%) 0 1/26 (3.8%) 1
    Investigations - Other, Elevated TSH 0/9 (0%) 0 1/26 (3.8%) 1
    Investigations - Other, Hemiparesis 0/9 (0%) 0 1/26 (3.8%) 1
    Lymphocyte count decreased 1/9 (11.1%) 1 1/26 (3.8%) 1
    Neutrophil count decreased 2/9 (22.2%) 5 3/26 (11.5%) 5
    Platelet count decreased 1/9 (11.1%) 1 4/26 (15.4%) 4
    Weight loss 2/9 (22.2%) 2 3/26 (11.5%) 3
    White blood cell decreased 3/9 (33.3%) 8 1/26 (3.8%) 2
    Metabolism and nutrition disorders
    Anorexia 2/9 (22.2%) 2 6/26 (23.1%) 6
    Dehydration 0/9 (0%) 0 1/26 (3.8%) 1
    Hyperglycemia 0/9 (0%) 0 1/26 (3.8%) 1
    Hypernatremia 1/9 (11.1%) 1 1/26 (3.8%) 1
    Hypoalbuminemia 1/9 (11.1%) 1 3/26 (11.5%) 3
    Hypocalcemia 1/9 (11.1%) 1 1/26 (3.8%) 1
    Hypokalemia 0/9 (0%) 0 2/26 (7.7%) 3
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/9 (11.1%) 1 1/26 (3.8%) 1
    Flank pain 1/9 (11.1%) 1 0/26 (0%) 0
    Muscle weakness left-sided 0/9 (0%) 0 2/26 (7.7%) 2
    Muscle weakness upper limb 0/9 (0%) 0 1/26 (3.8%) 1
    Pain in extremity 0/9 (0%) 0 2/26 (7.7%) 2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) 0/9 (0%) 0 1/26 (3.8%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) 0/9 (0%) 0 2/26 (7.7%) 2
    Nervous system disorders
    Ataxia 0/9 (0%) 0 1/26 (3.8%) 1
    Cognitive disturbance 3/9 (33.3%) 3 3/26 (11.5%) 3
    Dizziness 1/9 (11.1%) 1 2/26 (7.7%) 2
    Dysarthria 0/9 (0%) 0 1/26 (3.8%) 1
    Dysgeusia 3/9 (33.3%) 3 3/26 (11.5%) 3
    Dysphasia 1/9 (11.1%) 1 3/26 (11.5%) 3
    Extrapyramidal disorder 0/9 (0%) 0 1/26 (3.8%) 1
    Headache 2/9 (22.2%) 5 6/26 (23.1%) 7
    Memory impairment 0/9 (0%) 0 3/26 (11.5%) 3
    Nervous system disorders - Other, Skin sensitivity to touch 0/9 (0%) 0 1/26 (3.8%) 2
    Paresthesia 1/9 (11.1%) 1 0/26 (0%) 0
    Peripheral motor neuropathy 0/9 (0%) 0 1/26 (3.8%) 1
    Peripheral sensory neuropathy 0/9 (0%) 0 1/26 (3.8%) 1
    Seizure 3/9 (33.3%) 3 2/26 (7.7%) 3
    Spasticity 1/9 (11.1%) 1 1/26 (3.8%) 1
    Stroke 1/9 (11.1%) 1 0/26 (0%) 0
    Psychiatric disorders
    Anxiety 0/9 (0%) 0 1/26 (3.8%) 1
    Confusion 0/9 (0%) 0 2/26 (7.7%) 2
    Depression 1/9 (11.1%) 1 2/26 (7.7%) 2
    Insomnia 1/9 (11.1%) 1 0/26 (0%) 0
    Personality change 0/9 (0%) 0 1/26 (3.8%) 1
    Renal and urinary disorders
    Hematuria 1/9 (11.1%) 1 0/26 (0%) 0
    Urinary urgency 1/9 (11.1%) 1 0/26 (0%) 0
    Reproductive system and breast disorders
    Uterine hemorrhage 0/9 (0%) 1/26 (3.8%) 1
    Respiratory, thoracic and mediastinal disorders
    Cough 2/9 (22.2%) 2 2/26 (7.7%) 3
    Dyspnea 0/9 (0%) 0 1/26 (3.8%) 1
    Epistaxis 0/9 (0%) 0 1/26 (3.8%) 1
    Hoarseness 1/9 (11.1%) 1 0/26 (0%) 0
    Respiratory, thoracic and mediastinal disorders - Other, Congestion 1/9 (11.1%) 1 0/26 (0%) 0
    Respiratory, thoracic and mediastinal disorders - Other, Runny nose 0/9 (0%) 0 1/26 (3.8%) 1
    Sore throat 1/9 (11.1%) 1 0/26 (0%) 0
    Voice alteration 0/9 (0%) 0 1/26 (3.8%) 1
    Skin and subcutaneous tissue disorders
    Dry skin 1/9 (11.1%) 1 1/26 (3.8%) 1
    Purpura 1/9 (11.1%) 1 0/26 (0%) 0
    Rash maculo-papular 0/9 (0%) 0 1/26 (3.8%) 1
    Skin and subcutaneous tissue disorders - Other, Lacerations on legs 1/9 (11.1%) 1 0/26 (0%) 0
    Skin and subcutaneous tissue disorders - Other, specify 2/9 (22.2%) 6 0/26 (0%) 6
    Skin and subcutaneous tissue disorders - Other, Cushingoid facies-right cheek 0/9 (0%) 0 1/26 (3.8%) 1
    Skin and subcutaneous tissue disorders - Other, specify 0/9 (0%) 0 1/26 (3.8%) 1
    Skin hypopigmentation 0/9 (0%) 0 1/26 (3.8%) 1
    Vascular disorders
    Hypertension 7/9 (77.8%) 22 11/26 (42.3%) 27
    Hypotension 0/9 (0%) 0 1/26 (3.8%) 1

    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. Mark Gilbert
    Organization National Cancer Institute
    Phone 240-760-6023
    Email mark.gilbert@nih.gov
    Responsible Party:
    Mark Gilbert, M.D., Principal Investigator, National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01931098
    Other Study ID Numbers:
    • 160034
    • 16-C-0034
    First Posted:
    Aug 29, 2013
    Last Update Posted:
    Nov 24, 2020
    Last Verified:
    Nov 1, 2020