Bevacizumab With or Without Trebananib in Treating Patients With Recurrent Brain Tumors

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Active, not recruiting
CT.gov ID
NCT01609790
Collaborator
NRG Oncology (Other)
137
Enrollment
244
Locations
2
Arms
0.6
Patients Per Site

Study Details

Study Description

Brief Summary

This partially randomized phase II trial with a safety run-in component studies the side effects and how well bevacizumab given with or without trebananib works in treating patients with brain tumors that have come back (recurrent). Immunotherapy with monoclonal antibodies, such as bevacizumab, may induce changes in the body's immune system and interfere with the ability of tumor cells to grow and spread. Trebananib may stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether giving bevacizumab together with trebananib is more effective than bevacizumab alone in treating brain tumors.

Condition or DiseaseIntervention/TreatmentPhase
  • Biological: Bevacizumab
  • Other: Laboratory Biomarker Analysis
  • Other: Pharmacological Study
  • Other: Placebo Administration
  • Biological: Trebananib
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To assess the safety and tolerability of AMG 386 (trebananib) 15 mg/kg weekly in combination with bevacizumab 10 mg/kg every 2 weeks (Cohort 1). (closed to accrual 10/2/12)
  2. To assess the efficacy of AMG 386 in combination with bevacizumab 10 mg/kg every 2 weeks compared to bevacizumab monotherapy in bevacizumab-naive patients, as measured by 6-month progression-free survival (PFS6) (Cohort 2).
SECONDARY OBJECTIVES:
  1. To further assess the toxicity profile (Cohorts 1 and 2). II. To assess feasibility of AMG 386 15 mg/kg weekly in combination with bevacizumab 10 mg/kg every 2 weeks (Cohort 1 [closed to accrual 10/2/12]), as measured by the percentage of patients requiring dose reduction/interruption or discontinuation in the first 2 and subsequent cycles.

  2. To determine the radiographic response rate (RR), median progression-free survival (PFS), and overall survival (OS) in bevacizumab-naive patients (Cohort 2).

  3. To assess the efficacy of AMG 386 15 mg/kg weekly in combination with bevacizumab 10 mg/kg every 2 weeks in patients who have progressed while on bevacizumab, as measured by overall survival (OS) (cross-over from placebo arm of Cohort 2).

  4. To correlate outcome to treatment with tumor genotype, expression profile, and circulating angiogenesis biomarkers in tumor specimens (Cohort 2).

  5. To determine the RR, PFS6, and PFS in patients who have progressed while on bevacizumab therapy and receive AMG 386 in combination with bevacizumab (cross-over from placebo arm of Cohort 2).

  6. To determine the serum pharmacokinetics of AMG 386 in patients receiving bevacizumab (Cohort 1 and cross-over from placebo arm of Cohort 2).

OUTLINE: This is a safety study (cohort 1 [closed to accrual 10/2/12]) followed by a randomized study (cohort 2).

Cohort 1: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15 and trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. (closed to accrual 10/2/12)

Cohort 2: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive bevacizumab and trebananib as in Cohort 1.

ARM II: Patients receive bevacizumab as in Arm I and placebo IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm I.

After completion of study treatment, patients are followed up at 30 days, every 2 months for 1 year, every 6 months for 1 year, and then annually thereafter.

Study Design

Study Type:
Interventional
Actual Enrollment :
137 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Phase II Double-Blinded Placebo-Controlled Study of Bevacizumab With or Without AMG 386 in Patients With Recurrent Glioblastoma or Gliosarcoma
Actual Study Start Date :
Jun 4, 2012
Actual Primary Completion Date :
Oct 2, 2015

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm I (bevacizumab and trebananib)

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Bevacizumab
Given IV
Other Names:
  • ABP 215
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF rhuMAb
  • Avastin
  • Bevacizumab awwb
  • Bevacizumab Biosimilar ABP 215
  • Bevacizumab Biosimilar BEVZ92
  • Bevacizumab Biosimilar BI 695502
  • Bevacizumab Biosimilar CBT 124
  • Bevacizumab Biosimilar CT-P16
  • Bevacizumab Biosimilar FKB238
  • Bevacizumab Biosimilar GB-222
  • Bevacizumab Biosimilar HD204
  • Bevacizumab Biosimilar HLX04
  • Bevacizumab Biosimilar IBI305
  • Bevacizumab Biosimilar LY01008
  • Bevacizumab Biosimilar MIL60
  • Bevacizumab Biosimilar Mvasi
  • Bevacizumab Biosimilar MYL-1402O
  • Bevacizumab Biosimilar QL 1101
  • Bevacizumab Biosimilar RPH-001
  • Bevacizumab Biosimilar SCT501
  • Bevacizumab Biosimilar Zirabev
  • Bevacizumab-awwb
  • Bevacizumab-bvzr
  • BP102
  • BP102 Biosimilar
  • HD204
  • Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
  • Mvasi
  • MYL-1402O
  • Recombinant Humanized Anti-VEGF Monoclonal Antibody
  • rhuMab-VEGF
  • SCT501
  • Zirabev
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Other: Pharmacological Study
    Correlative studies

    Biological: Trebananib
    Given IV
    Other Names:
  • AMG 386
  • AMG386
  • Angiopoietin 1/2-Neutralizing Peptibody AMG 386
  • Active Comparator: Arm II (bevacizumab and placebo)

    Patients receive bevacizumab as in Arm I and placebo IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm I.

    Biological: Bevacizumab
    Given IV
    Other Names:
  • ABP 215
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF rhuMAb
  • Avastin
  • Bevacizumab awwb
  • Bevacizumab Biosimilar ABP 215
  • Bevacizumab Biosimilar BEVZ92
  • Bevacizumab Biosimilar BI 695502
  • Bevacizumab Biosimilar CBT 124
  • Bevacizumab Biosimilar CT-P16
  • Bevacizumab Biosimilar FKB238
  • Bevacizumab Biosimilar GB-222
  • Bevacizumab Biosimilar HD204
  • Bevacizumab Biosimilar HLX04
  • Bevacizumab Biosimilar IBI305
  • Bevacizumab Biosimilar LY01008
  • Bevacizumab Biosimilar MIL60
  • Bevacizumab Biosimilar Mvasi
  • Bevacizumab Biosimilar MYL-1402O
  • Bevacizumab Biosimilar QL 1101
  • Bevacizumab Biosimilar RPH-001
  • Bevacizumab Biosimilar SCT501
  • Bevacizumab Biosimilar Zirabev
  • Bevacizumab-awwb
  • Bevacizumab-bvzr
  • BP102
  • BP102 Biosimilar
  • HD204
  • Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
  • Mvasi
  • MYL-1402O
  • Recombinant Humanized Anti-VEGF Monoclonal Antibody
  • rhuMab-VEGF
  • SCT501
  • Zirabev
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Other: Pharmacological Study
    Correlative studies

    Other: Placebo Administration
    Given IV

    Outcome Measures

    Primary Outcome Measures

    1. Number of Patients Experiencing of Dose-limiting Toxicity (Cohort 1) [From start of treatment to 4 weeks.]

      Dose-limiting toxicity (DLT), defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications and meets any of the criteria below. Any DLT must be a toxicity possibly related to protocol treatment during first 4 weeks: grade 4 hematologic toxicity, grade 3/4 thrombocytopenia, or grade 3/4 non-hematologic toxicity; Gastrointestinal fistula, bowel perforation, intracranial hemorrhage, wound dehiscence, or reversible posterior leukoencephalopathy of any grade; Delay of treatment > 28 days. If 2+ of patients experience a DLT among 6 eligible patients, this drug combination will be considered unsafe and a lower dose of AMG will be explored; otherwise conclude that this drug combination is safe. The probability of claiming safe dose is no more than 16% when the true DLT rate is >45%, and the probability of claiming safe dose is at least 78% when the true DLT rate is <= 15%.

    2. Six-month Progression-free Survival (Cohort 2) [From randomization to six months.]

      As determined by central review of MRI exams, assessed using RANO criteria for progression that is defined by any of the following: > 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared to the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids; Significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared to baseline scan or best response following initiation of therapy, not due to co-morbid events; Any new lesion; Clear clinical deterioration not attributable to other causes apart from the tumor or changes in corticosteroid dose; Failure to return for evaluation due to death or deteriorating condition; Clear progression of non-measurable disease.

    Secondary Outcome Measures

    1. Incidence of Grade 3+ Treatment-related Toxicity, Measured by CTCAE v. 4 (Cohort 2) [From start of treatment up to 3 years.]

      Adverse events (AEs) are graded by using CTCAE 4.0. Possibly/probably/definitely related to protocol treatment AEs are considered.

    2. Overall Survival (Cohort 2) [From randomization up to 3 years.]

      Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. This analysis was planned to occur when all patients had been potentially followed for at least 6 months.

    3. Progression-free Survival (Cohort 2) [From randomization up to 3 years.]

      Progression-free survival time is measured from randomization to the date of first progression or death or, otherwise, the last follow-up date on which the patient was reported alive. This analysis was planned to occur when all patients had been potentially followed for at least 6 months.

    4. Radiographic Response Rate (Cohort 2) [From randomization up to 3 years.]

      Proportion of patients with best overall response of complete response (CR) or partial response (PR) recorded from the start of the treatment until disease progression/recurrence. Response determined by site-reported radiology review of MRI exams using Response Assessment in Neuro-Oncology Criteria (RANO) criteria. CR: Complete disappearance of all enhancing measurable disease (MD) + non-measurable disease (NMD) sustained >= 4 wks; No new lesions; Stable or improved non-enhancing (T2/FLAIR) lesions; Off corticosteroids (or on physiologic replacement doses only); Stable/improved clinically. PR: >= 50% decrease vs. baseline of sum of products of perpendicular diameters of all measurable enhancing lesions sustained >= 4 wks; No progression of NMD; No new lesions; Stable/improved non-enhancing (T2/FLAIR) lesions on <= dose of corticosteroids vs. baseline scan; Corticosteroid dose at evaluation scan <= baseline scan dose; Stable or improved clinically. NMD only cannot be a CR or PR.

    5. Percentage of Patients Requiring Dose Reduction/Interruption or Discontinuation in the First 2 and Subsequent Courses (Cohort 1) [From randomization up to 3 years.]

      Feasibility of trebananib weekly in combination with bevacizumab every 2 weeks, measured by the percentage of patients requiring dose reduction/interruption or discontinuation in the first 2 and subsequent courses (Cohort 1)

    Other Outcome Measures

    1. Tumor Genotype, Expression Profile, and Circulating Angiogenesis Biomarkers (Cohort 2) [From randomization to date of death or last followup. Statistical analysis occurs when tumor genotype, expression profile and circulating angiogenesis biomarkers have been determined from the tissue specimens.]

      Biomarker data has not yet been obtained and therefore this outcome measure cannot yet be reported.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically proven diagnosis of glioblastoma or variants (gliosarcoma, glioblastoma with oligodendroglial features, giant cell glioblastoma); patients will be eligible if the original histology was a lower grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made

    • The tumor must be supratentorial; patients with infratentorial disease, spinal cord disease, and/or leptomeningeal disease are excluded

    • Patients must have shown unequivocal evidence for tumor progression on the previous treatment regimen (prior to enrollment on this study) by magnetic resonance imaging (MRI) scan of the brain with and without contrast within 14 days prior to registration; the dose of steroids must be stable or decreasing for at least 5 days prior to the scan; patients with tumor progression who then undergo surgical resection prior to enrollment on study may be eligible as long as pathology confirms progressive or recurrent glioblastoma multiforme (GBM) (or variants); for patients who undergo surgical resection, registration on study may not occur any sooner than 28 days from surgery; an MRI scan of the brain with and without contrast is still required within 14 days prior to registration on study but is not required to demonstrate measurable disease or tumor progression after surgery

    • Patients unable to undergo MRI because of non-compatible devices can be enrolled, provided computed tomography (CT) scans are obtained and are of sufficient quality; patients without non-compatible devices may not have CT scans performed to meet this requirement

    • History/physical examination within 14 days prior to registration

    • Karnofsky performance scale >= 70 within 14 days prior to registration

    • Patients who have received prior treatment with interstitial brachytherapy, stereotactic radiosurgery, or implanted chemotherapy sources, such as wafers of polifeprosan 20 with carmustine, must have confirmation of progressive disease within 14 days prior to registration based upon nuclear imaging, magnetic resonance (MR) spectroscopy, perfusion imaging, or histopathology

    • Leukocytes > 3,000/mm^3 (within 14 days prior to registration)

    • Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 14 days prior to registration)

    • Hemoglobin >= 10.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dL is acceptable) (within 14 days prior to registration)

    • Platelets >= 100,000 cells/mm^3 (within 14 days prior to registration)

    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 X institutional upper limit of normal (within 14 days prior to registration)

    • Bilirubin =< 2.0 mg/dL (within 14 days prior to registration)

    • Creatinine within normal upper institutional limits or creatinine clearance > 60 mL/min/1.73 m^2 (per 24 hour urine collection or calculated according to the Cockcroft-Gault formula) for subjects with creatinine levels above the institutional normal (within 14 days prior to registration)

    • Patients with creatinine levels below normal institutional limits are eligible

    • Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 (within 14 days prior to registration)

    • Urinary protein =< 30 mg/dL in urinalysis or =< 1+ on dipstick (within 14 days prior to registration)

    • Generally well-controlled blood pressure with systolic blood pressure =< 140 mm Hg AND diastolic blood pressure =< 90 mm Hg within 5 days prior to registration; the use of anti-hypertensive medications to control hypertension is permitted

    • Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (HCG) pregnancy test within 14 days prior to registration

    • Women of childbearing potential and male patients who are sexually active must practice adequate contraception during therapy and for 180 days (6 months) afterwards

    • Patient must provide study specific informed consent prior to study entry

    Exclusion Criteria:
    • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)

    • Prior systemic cytotoxic chemotherapy within (i.e., =<) 28 days (42 days for nitrosoureas or mitomycin C) prior to registration, or patients who have not returned to baseline or =< Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v.

    1. grade 2 from adverse events (excluding alopecia) due to agents administered more than 28 days prior to registration
    • Patients who received non-cytotoxic drug therapy must be off treatment for at least 14 days prior to registration; prior treatment with anti-vascular endothelial growth factor (VEGF) targeted agents; AMG 386 therapy; or other molecules that inhibit angiopoietins or TEK tyrosine kinase, endothelial (Tie2) receptor including, but not limited to, XL-820, XL-184 (cabozantinib-s-malate), and CVX-060/PF-4856884 is not allowed regardless of time frame

    • Patients who have not yet completed at least 21 days (30 days for prior monoclonal antibody therapy) since ending other investigational device or drug trials, or who are currently receiving other investigational treatments

    • Treatment within 30 days prior to enrollment with strong immune modulators, including but not limited to systemic cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, methotrexate, azathioprine, rapamycin, thalidomide, lenalidomide, and targeted immune modulators such as abatacept (CTLA-4-Ig), adalimumab, alefacept, anakinra, belatacept (LEA29Y), efalizumab, etanercept, infliximab, or rituximab

    • Prior radiotherapy within 90 days (3 months) prior to registration unless there is either: a) histopathologic confirmation of recurrent tumor; or b) new enhancement on MRI outside of the radiation treatment field

    • Major surgical procedure (including craniotomy and open brain biopsy) or significant traumatic injury within 28 days prior to registration or those patients who receive a non-central nervous system (CNS) minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 3 days prior to registration; there is no waiting period for central line placement; there is a 7-day window for recovery prior to registration for patients who underwent stereotactic biopsy of the brain

    • Prior therapy with anti-VEGF targeted agents (e.g. bevacizumab, cediranib, vandetanib, aflibercept, sunitinib, sorafenib, etc.); prior therapy with thalidomide and lenalidomide is allowed as long as treatment has not occurred within 30 days prior to enrollment

    • More than 2 relapses

    • Therapeutic anticoagulation with warfarin < 7 days prior to registration; (therapeutic or prophylactic therapy with aspirin, a low-molecular weight heparin, or a Factor Xa inhibitor is acceptable)

    • Intratumoral hemorrhage or peritumoral hemorrhage, demonstrated by MRI or CT scan, CTCAE, v. 4 grade 2 or greater or evidence of significant hemorrhage (regardless of CTCAE, v. 4 grade) defined as > 1 cm diameter of blood (including postoperative hemorrhage)

    • Gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE, v. 4 grade 3 or greater within 30 days prior to study entry

    • Severe, active co-morbidity, defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within 180 days (6 months) prior to registration

    • Transmural myocardial infarction within 180 days (6 months) prior to registration

    • History of stroke, cerebral vascular accident (CVA), or transient ischemic attack within 180 days (6 months) prior to registration

    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

    • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol

    • Known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhages in the past

    • History of non-healing wounds or ulcers, or bone fractures within 90 days (3 months) prior to registration

    • History of venous or arterial thromboembolism within 12 months prior to registration

    • Prior allergic reaction to the study drugs involved in this study

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Alaska Breast Care and Surgery LLCAnchorageAlaskaUnited States99508
    2Alaska Women's Cancer CareAnchorageAlaskaUnited States99508
    3Anchorage Oncology CentreAnchorageAlaskaUnited States99508
    4Katmai Oncology GroupAnchorageAlaskaUnited States99508
    5Providence Alaska Medical CenterAnchorageAlaskaUnited States99508
    6Arizona Oncology-Deer Valley CenterPhoenixArizonaUnited States85027
    7Arizona Oncology Services FoundationScottsdaleArizonaUnited States85260
    8Arizona Oncology Associates-West Orange GroveTucsonArizonaUnited States85704
    9Alta Bates Summit Medical Center-Herrick CampusBerkeleyCaliforniaUnited States94704
    10Mills-Peninsula Medical CenterBurlingameCaliforniaUnited States94010
    11Kaiser Permanente Los Angeles Medical CenterLos AngelesCaliforniaUnited States90027
    12Los Angeles County-USC Medical CenterLos AngelesCaliforniaUnited States90033
    13USC / Norris Comprehensive Cancer CenterLos AngelesCaliforniaUnited States90033
    14Sutter Cancer Research ConsortiumNovatoCaliforniaUnited States94945
    15Saint Joseph Hospital - OrangeOrangeCaliforniaUnited States92868
    16UC Irvine Health/Chao Family Comprehensive Cancer CenterOrangeCaliforniaUnited States92868
    17California Pacific Medical Center-Pacific CampusSan FranciscoCaliforniaUnited States94115
    18Sutter Solano Medical Center/Cancer CenterVallejoCaliforniaUnited States94589
    19Poudre Valley HospitalFort CollinsColoradoUnited States80524
    20Smilow Cancer Hospital Care Center at Saint FrancisHartfordConnecticutUnited States06105
    21The Hospital of Central ConnecticutNew BritainConnecticutUnited States06050
    22Eastern Connecticut Hematology and Oncology AssociatesNorwichConnecticutUnited States06360
    23William Backus HospitalNorwichConnecticutUnited States06360
    24Broward Health Medical CenterFort LauderdaleFloridaUnited States33316
    25Piedmont HospitalAtlantaGeorgiaUnited States30309
    26Piedmont Fayette HospitalFayettevilleGeorgiaUnited States30214
    27Northeast Georgia Medical Center-GainesvilleGainesvilleGeorgiaUnited States30501
    28Saint Alphonsus Cancer Care Center-BoiseBoiseIdahoUnited States83706
    29Rush - Copley Medical CenterAuroraIllinoisUnited States60504
    30Northwestern UniversityChicagoIllinoisUnited States60611
    31Rush University Medical CenterChicagoIllinoisUnited States60612
    32University of Chicago Comprehensive Cancer CenterChicagoIllinoisUnited States60637
    33Carle on VermilionDanvilleIllinoisUnited States61832
    34Heartland Cancer Research NCORPDecaturIllinoisUnited States62526
    35Carle Physician Group-EffinghamEffinghamIllinoisUnited States62401
    36NorthShore University HealthSystem-Evanston HospitalEvanstonIllinoisUnited States60201
    37Illinois CancerCare-GalesburgGalesburgIllinoisUnited States61401
    38NorthShore University HealthSystem-Glenbrook HospitalGlenviewIllinoisUnited States60026
    39Carle Physician Group-Mattoon/CharlestonMattoonIllinoisUnited States61938
    40Good Samaritan Regional Health CenterMount VernonIllinoisUnited States62864
    41Carle Cancer Institute NormalNormalIllinoisUnited States61761
    42OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment CenterPekinIllinoisUnited States61554
    43Illinois CancerCare-PeoriaPeoriaIllinoisUnited States61615
    44OSF Saint Francis Radiation Oncology at Peoria Cancer CenterPeoriaIllinoisUnited States61615
    45Methodist Medical Center of IllinoisPeoriaIllinoisUnited States61636
    46OSF Saint Francis Medical CenterPeoriaIllinoisUnited States61637
    47Carle Cancer CenterUrbanaIllinoisUnited States61801
    48The Carle Foundation HospitalUrbanaIllinoisUnited States61801
    49Northwestern Medicine Cancer Center WarrenvilleWarrenvilleIllinoisUnited States60555
    50Rush-Copley Healthcare CenterYorkvilleIllinoisUnited States60560
    51Menorah Medical CenterOverland ParkKansasUnited States66209
    52Saint Luke's South HospitalOverland ParkKansasUnited States66213
    53Kansas City NCI Community Oncology Research ProgramPrairie VillageKansasUnited States66208
    54University of Kentucky/Markey Cancer CenterLexingtonKentuckyUnited States40536
    55Maine Medical Center- Scarborough CampusScarboroughMaineUnited States04074
    56Michigan Cancer Research Consortium NCORPAnn ArborMichiganUnited States48106
    57Saint Joseph Mercy HospitalAnn ArborMichiganUnited States48106
    58Beaumont Hospital - DearbornDearbornMichiganUnited States48124
    59Ascension Saint John HospitalDetroitMichiganUnited States48236
    60Green Bay Oncology - EscanabaEscanabaMichiganUnited States49829
    61Genesys Hurley Cancer InstituteFlintMichiganUnited States48503
    62Hurley Medical CenterFlintMichiganUnited States48503
    63Green Bay Oncology - Iron MountainIron MountainMichiganUnited States49801
    64Bronson Methodist HospitalKalamazooMichiganUnited States49007
    65West Michigan Cancer CenterKalamazooMichiganUnited States49007
    66Borgess Medical CenterKalamazooMichiganUnited States49048
    67Sparrow HospitalLansingMichiganUnited States48912
    68Saint Mary Mercy HospitalLivoniaMichiganUnited States48154
    69Saint Joseph Mercy OaklandPontiacMichiganUnited States48341
    70Lake Huron Medical CenterPort HuronMichiganUnited States48060
    71William Beaumont Hospital-Royal OakRoyal OakMichiganUnited States48073
    72Ascension Saint Mary's HospitalSaginawMichiganUnited States48601
    73William Beaumont Hospital - TroyTroyMichiganUnited States48085
    74Saint John Macomb-Oakland HospitalWarrenMichiganUnited States48093
    75Fairview Ridges HospitalBurnsvilleMinnesotaUnited States55337
    76Mercy HospitalCoon RapidsMinnesotaUnited States55433
    77Fairview Southdale HospitalEdinaMinnesotaUnited States55435
    78Unity HospitalFridleyMinnesotaUnited States55432
    79Hutchinson Area Health CareHutchinsonMinnesotaUnited States55350
    80Minnesota Oncology Hematology PA-MaplewoodMaplewoodMinnesotaUnited States55109
    81Saint John's Hospital - HealtheastMaplewoodMinnesotaUnited States55109
    82Abbott-Northwestern HospitalMinneapolisMinnesotaUnited States55407
    83Hennepin County Medical CenterMinneapolisMinnesotaUnited States55415
    84Health Partners IncMinneapolisMinnesotaUnited States55454
    85North Memorial Medical Health CenterRobbinsdaleMinnesotaUnited States55422
    86Metro Minnesota Community Oncology Research ConsortiumSaint Louis ParkMinnesotaUnited States55416
    87Park Nicollet Clinic - Saint Louis ParkSaint Louis ParkMinnesotaUnited States55416
    88Regions HospitalSaint PaulMinnesotaUnited States55101
    89United HospitalSaint PaulMinnesotaUnited States55102
    90Saint Francis Regional Medical CenterShakopeeMinnesotaUnited States55379
    91Ridgeview Medical CenterWaconiaMinnesotaUnited States55387
    92Rice Memorial HospitalWillmarMinnesotaUnited States56201
    93Minnesota Oncology Hematology PA-WoodburyWoodburyMinnesotaUnited States55125
    94University of Mississippi Medical CenterJacksonMississippiUnited States39216
    95Singing River HospitalPascagoulaMississippiUnited States39581
    96Saint Francis Medical CenterCape GirardeauMissouriUnited States63703
    97Centerpoint Medical Center LLCIndependenceMissouriUnited States64057
    98Freeman Health SystemJoplinMissouriUnited States64804
    99Mercy Hospital JoplinJoplinMissouriUnited States64804
    100Saint Luke's Hospital of Kansas CityKansas CityMissouriUnited States64111
    101North Kansas City HospitalKansas CityMissouriUnited States64116
    102Heartland Hematology and Oncology Associates IncorporatedKansas CityMissouriUnited States64118
    103Research Medical CenterKansas CityMissouriUnited States64132
    104Saint Luke's East - Lee's SummitLee's SummitMissouriUnited States64086
    105Liberty Radiation Oncology CenterLibertyMissouriUnited States64068
    106Mercy Clinic-Rolla-Cancer and HematologyRollaMissouriUnited States65401
    107Heartland Regional Medical CenterSaint JosephMissouriUnited States64506
    108Saint Joseph Oncology IncSaint JosephMissouriUnited States64507
    109Saint Louis Cancer and Breast Institute-South CitySaint LouisMissouriUnited States63109
    110Mercy Hospital Saint LouisSaint LouisMissouriUnited States63141
    111Cancer Research for the Ozarks NCORPSpringfieldMissouriUnited States65804
    112Mercy Hospital SpringfieldSpringfieldMissouriUnited States65804
    113CoxHealth South HospitalSpringfieldMissouriUnited States65807
    114Nebraska Methodist HospitalOmahaNebraskaUnited States68114
    115New York Oncology Hematology PC - AlbanyAlbanyNew YorkUnited States12206
    116New York Oncology Hematology PC - Albany Medical CenterAlbanyNew YorkUnited States12208
    117Hematology Oncology Associates of Central New York-AuburnAuburnNew YorkUnited States13021
    118Montefiore Medical Center - Moses CampusBronxNew YorkUnited States10467
    119Hematology Oncology Associates of Central New York-East SyracuseEast SyracuseNew YorkUnited States13057
    120Hematology Oncology Associates of Central New York-LiverpoolLiverpoolNew YorkUnited States13088
    121Laura and Isaac Perlmutter Cancer Center at NYU LangoneNew YorkNew YorkUnited States10016
    122NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer CenterNew YorkNew YorkUnited States10032
    123Hematology Oncology Associates of Central New York-RomeRomeNew YorkUnited States13440
    124Hematology Oncology Associates of Central New York-Onondaga HillSyracuseNew YorkUnited States13215
    125Mission HospitalAshevilleNorth CarolinaUnited States28801
    126Mountain Radiation Oncology PAAshevilleNorth CarolinaUnited States28801
    127AdventHealth Infusion Center AshevilleAshevilleNorth CarolinaUnited States28803
    128Messino Cancer CentersAshevilleNorth CarolinaUnited States28806
    129AdventHealth HendersonvilleHendersonvilleNorth CarolinaUnited States28792
    130Rutherford HospitalRutherfordtonNorth CarolinaUnited States28139
    131Southeast Clinical Oncology Research Consortium NCORPWinston-SalemNorth CarolinaUnited States27104
    132Summa Health System - Akron CampusAkronOhioUnited States44304
    133Cleveland Clinic Akron GeneralAkronOhioUnited States44307
    134Summa Health System - Barberton CampusBarbertonOhioUnited States44203
    135Strecker Cancer Center-BelpreBelpreOhioUnited States45714
    136Adena Regional Medical CenterChillicotheOhioUnited States45601
    137University of Cincinnati Cancer Center-UC Medical CenterCincinnatiOhioUnited States45219
    138Columbus Oncology and Hematology Associates IncColumbusOhioUnited States43214
    139Riverside Methodist HospitalColumbusOhioUnited States43214
    140Columbus NCI Community Oncology Research ProgramColumbusOhioUnited States43215
    141Grant Medical CenterColumbusOhioUnited States43215
    142The Mark H Zangmeister CenterColumbusOhioUnited States43219
    143Mount Carmel Health Center WestColumbusOhioUnited States43222
    144Doctors HospitalColumbusOhioUnited States43228
    145Delaware Health Center-Grady Cancer CenterDelawareOhioUnited States43015
    146Delaware Radiation OncologyDelawareOhioUnited States43015
    147Grady Memorial HospitalDelawareOhioUnited States43015
    148Fairfield Medical CenterLancasterOhioUnited States43130
    149Lancaster Radiation OncologyLancasterOhioUnited States43130
    150Marietta Memorial HospitalMariettaOhioUnited States45750
    151Summa Health Medina Medical CenterMedinaOhioUnited States44256
    152Knox Community HospitalMount VernonOhioUnited States43050
    153Licking Memorial HospitalNewarkOhioUnited States43055
    154Newark Radiation OncologyNewarkOhioUnited States43055
    155Southern Ohio Medical CenterPortsmouthOhioUnited States45662
    156University Hospitals Portage Medical CenterRavennaOhioUnited States44266
    157Springfield Regional Medical CenterSpringfieldOhioUnited States45505
    158University of Cincinnati Cancer Center-West ChesterWest ChesterOhioUnited States45069
    159Saint Ann's HospitalWestervilleOhioUnited States43081
    160Genesis Healthcare System Cancer Care CenterZanesvilleOhioUnited States43701
    161University of Oklahoma Health Sciences CenterOklahoma CityOklahomaUnited States73104
    162Natalie Warren Bryant Cancer Center at Saint FrancisTulsaOklahomaUnited States74136
    163Oklahoma Cancer Specialists and Research Institute-TulsaTulsaOklahomaUnited States74146
    164Warren Clinic Oncology-TulsaTulsaOklahomaUnited States74146
    165Clackamas Radiation Oncology CenterClackamasOregonUnited States97015
    166Willamette Valley Cancer CenterEugeneOregonUnited States97401
    167Providence Portland Medical CenterPortlandOregonUnited States97213
    168Providence Saint Vincent Medical CenterPortlandOregonUnited States97225
    169UPMC-Heritage Valley Health System BeaverBeaverPennsylvaniaUnited States15009
    170Saint Luke's University Hospital-Bethlehem CampusBethlehemPennsylvaniaUnited States18015
    171Bryn Mawr HospitalBryn MawrPennsylvaniaUnited States19010
    172UPMC Cancer Center at UPMC HorizonFarrellPennsylvaniaUnited States16121
    173Adams Cancer CenterGettysburgPennsylvaniaUnited States17325
    174UPMC Cancer Centers - Arnold Palmer PavilionGreensburgPennsylvaniaUnited States15601
    175Cherry Tree Cancer CenterHanoverPennsylvaniaUnited States17331
    176UPMC-Johnstown/John P. Murtha Regional Cancer CenterJohnstownPennsylvaniaUnited States15901
    177Lancaster General HospitalLancasterPennsylvaniaUnited States17602
    178UPMC Cancer Center at UPMC McKeesportMcKeesportPennsylvaniaUnited States15132
    179UPMC Cancer Center-Natrona HeightsNatrona HeightsPennsylvaniaUnited States15065
    180UPMC JamesonNew CastlePennsylvaniaUnited States16105
    181Paoli Memorial HospitalPaoliPennsylvaniaUnited States19301
    182Thomas Jefferson University HospitalPhiladelphiaPennsylvaniaUnited States19107
    183UPMC-Presbyterian HospitalPittsburghPennsylvaniaUnited States15213
    184UPMC-Saint MargaretPittsburghPennsylvaniaUnited States15215
    185UPMC-Shadyside HospitalPittsburghPennsylvaniaUnited States15232
    186UPMC Jefferson Regional Radiation OncologyPittsburghPennsylvaniaUnited States15236
    187UPMC-Passavant HospitalPittsburghPennsylvaniaUnited States15237
    188UPMC-Saint Clair Hospital Cancer CenterPittsburghPennsylvaniaUnited States15243
    189UPMC Cancer Center at UPMC NorthwestSenecaPennsylvaniaUnited States16346
    190UPMC Uniontown Hospital Radiation OncologyUniontownPennsylvaniaUnited States15401
    191UPMC Washington Hospital Radiation OncologyWashingtonPennsylvaniaUnited States15301
    192Reading HospitalWest ReadingPennsylvaniaUnited States19611
    193Lankenau Medical CenterWynnewoodPennsylvaniaUnited States19096
    194Main Line Health NCORPWynnewoodPennsylvaniaUnited States19096
    195WellSpan Health-York HospitalYorkPennsylvaniaUnited States17403
    196AnMed Health Cancer CenterAndersonSouth CarolinaUnited States29621
    197Gibbs Cancer Center-PelhamGreerSouth CarolinaUnited States29651
    198Spartanburg Medical CenterSpartanburgSouth CarolinaUnited States29303
    199Rapid City Regional HospitalRapid CitySouth DakotaUnited States57701
    200Texas Oncology-Austin MidtownAustinTexasUnited States78705
    201Texas Oncology - Central Austin Cancer CenterAustinTexasUnited States78731
    202Texas Oncology - South Austin Cancer CenterAustinTexasUnited States78745
    203Texas Oncology BedfordBedfordTexasUnited States76022
    204Texas Oncology at Baylor Charles A Sammons Cancer CenterDallasTexasUnited States75246
    205UT Southwestern/Simmons Cancer Center-DallasDallasTexasUnited States75390
    206Texas Oncology - Fort Worth Cancer CenterFort WorthTexasUnited States76104
    207Texas Oncology-GrapevineGrapevineTexasUnited States76053
    208Texas Oncology-Longview Cancer CenterLongviewTexasUnited States75601
    209Texas Oncology-Seton WilliamsonRound RockTexasUnited States78665
    210Texas Oncology - Round Rock Cancer CenterRound RockTexasUnited States78681
    211Texas Oncology Cancer Center Sugar LandSugar LandTexasUnited States77479
    212Tyler Cancer CenterTylerTexasUnited States75702
    213American Fork Hospital / Huntsman Intermountain Cancer CenterAmerican ForkUtahUnited States84003
    214Sandra L Maxwell Cancer CenterCedar CityUtahUnited States84720
    215Logan Regional HospitalLoganUtahUnited States84321
    216Intermountain Medical CenterMurrayUtahUnited States84107
    217McKay-Dee Hospital CenterOgdenUtahUnited States84403
    218Utah Valley Regional Medical CenterProvoUtahUnited States84604
    219Dixie Medical Center Regional Cancer CenterSaint GeorgeUtahUnited States84770
    220Utah Cancer Specialists-Salt Lake CitySalt Lake CityUtahUnited States84106
    221LDS HospitalSalt Lake CityUtahUnited States84143
    222Cancer Care Northwest - Spokane SouthSpokaneWashingtonUnited States99202
    223Cancer Care Northwest-North SpokaneSpokaneWashingtonUnited States99218
    224PeaceHealth Southwest Medical CenterVancouverWashingtonUnited States98664
    225Compass Oncology VancouverVancouverWashingtonUnited States98684
    226Langlade Hospital and Cancer CenterAntigoWisconsinUnited States54409
    227Green Bay Oncology at Saint Vincent HospitalGreen BayWisconsinUnited States54301-3526
    228Saint Vincent Hospital Cancer Center Green BayGreen BayWisconsinUnited States54301
    229Green Bay Oncology Limited at Saint Mary's HospitalGreen BayWisconsinUnited States54303
    230Saint Vincent Hospital Cancer Center at Saint Mary'sGreen BayWisconsinUnited States54303
    231University of Wisconsin Hospital and ClinicsMadisonWisconsinUnited States53792
    232Holy Family Memorial HospitalManitowocWisconsinUnited States54221
    233Bay Area Medical CenterMarinetteWisconsinUnited States54143
    234Froedtert Menomonee Falls HospitalMenomonee FallsWisconsinUnited States53051
    235Medical College of WisconsinMilwaukeeWisconsinUnited States53226
    236ProHealth D N Greenwald CenterMukwonagoWisconsinUnited States53149
    237Cancer Center of Western WisconsinNew RichmondWisconsinUnited States54017
    238ProHealth Oconomowoc Memorial HospitalOconomowocWisconsinUnited States53066
    239Saint Vincent Hospital Cancer Center at Oconto FallsOconto FallsWisconsinUnited States54154
    240Saint Vincent Hospital Cancer Center at Sturgeon BaySturgeon BayWisconsinUnited States54235-1495
    241Green Bay Oncology - Sturgeon BaySturgeon BayWisconsinUnited States54235
    242ProHealth Waukesha Memorial HospitalWaukeshaWisconsinUnited States53188
    243Aspirus Regional Cancer CenterWausauWisconsinUnited States54401
    244Allan Blair Cancer CentreReginaSaskatchewanCanadaS4T 7T1

    Sponsors and Collaborators

    • National Cancer Institute (NCI)
    • NRG Oncology

    Investigators

    • Principal Investigator: Eudocia Q Lee, NRG Oncology

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01609790
    Other Study ID Numbers:
    • NCI-2012-01969
    • NCI-2012-01969
    • S13-00759
    • CDR0000734205
    • RTOG-1122
    • RTOG-1122
    • RTOG-1122
    • U10CA180868
    • U10CA021661
    First Posted:
    Jun 1, 2012
    Last Update Posted:
    Dec 22, 2021
    Last Verified:
    Dec 1, 2021

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleCohort 1: Safety Run-InCohort 2: Bevacizumab+PlaceboCohort 2: Bevacizumab+AMG 386
    Arm/Group DescriptionBevacizumab every 2 weeks + AMG 386 weekly until disease progression.Bevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
    Period Title: Overall Study
    STARTED76565
    COMPLETED65857
    NOT COMPLETED178

    Baseline Characteristics

    Arm/Group TitleCohort 1: Safety Run-InCohort 2: Bevacizumab+PlaceboCohort 2: Bevacizumab+AMG 386Total
    Arm/Group DescriptionBevacizumab every 2 weeks + AMG 386 weekly until disease progression.Bevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.Total of all reporting groups
    Overall Participants65857121
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    56
    58
    57
    58
    Sex: Female, Male (Count of Participants)
    Female
    1
    16.7%
    22
    37.9%
    25
    43.9%
    48
    39.7%
    Male
    5
    83.3%
    36
    62.1%
    32
    56.1%
    73
    60.3%

    Outcome Measures

    1. Primary Outcome
    TitleNumber of Patients Experiencing of Dose-limiting Toxicity (Cohort 1)
    DescriptionDose-limiting toxicity (DLT), defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications and meets any of the criteria below. Any DLT must be a toxicity possibly related to protocol treatment during first 4 weeks: grade 4 hematologic toxicity, grade 3/4 thrombocytopenia, or grade 3/4 non-hematologic toxicity; Gastrointestinal fistula, bowel perforation, intracranial hemorrhage, wound dehiscence, or reversible posterior leukoencephalopathy of any grade; Delay of treatment > 28 days. If 2+ of patients experience a DLT among 6 eligible patients, this drug combination will be considered unsafe and a lower dose of AMG will be explored; otherwise conclude that this drug combination is safe. The probability of claiming safe dose is no more than 16% when the true DLT rate is >45%, and the probability of claiming safe dose is at least 78% when the true DLT rate is <= 15%.
    Time FrameFrom start of treatment to 4 weeks.

    Outcome Measure Data

    Analysis Population Description
    All eligible patients who started study treatment
    Arm/Group TitleSafety Run-In
    Arm/Group DescriptionBevacizumab every 2 weeks + AMG 386 weekly until disease progression.
    Measure Participants6
    Number [participants]
    0
    0%
    2. Primary Outcome
    TitleSix-month Progression-free Survival (Cohort 2)
    DescriptionAs determined by central review of MRI exams, assessed using RANO criteria for progression that is defined by any of the following: > 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared to the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids; Significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared to baseline scan or best response following initiation of therapy, not due to co-morbid events; Any new lesion; Clear clinical deterioration not attributable to other causes apart from the tumor or changes in corticosteroid dose; Failure to return for evaluation due to death or deteriorating condition; Clear progression of non-measurable disease.
    Time FrameFrom randomization to six months.

    Outcome Measure Data

    Analysis Population Description
    Randomized patients evaluable for 6 months progression-free survival (PFS).
    Arm/Group TitleCohort 2: Bevacizumab+PlaceboCohort 2: Bevacizumab+AMG 386
    Arm/Group DescriptionBevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
    Measure Participants5653
    Number (95% Confidence Interval) [percentage of participants]
    41.1
    685%
    22.6
    39%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Safety Run-In, Cohort 2: Bevacizumab+AMG 386
    Comments Assuming a 36% 6-month (6m) rate in the placebo arm [from the March 2009 Food and Drug Administration (FDA) briefing], a 55% rate in the AMG 386 arm, and an exponential distribution corresponds to median PFS of 4.1 and 7 months, respectively, with a hazard ratio of 0.59 (AMG 386 arm vs. placebo arm). A total of 114 patients (57 per arm) will yield 85% power to detect an absolute 19% difference of 6m PFS rate at a 1-sided alpha level of 0.15 based on a 2-sample proportion test.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.98
    Comments
    MethodZ-test
    CommentsOne-sided test, significance level 0.15
    3. Secondary Outcome
    TitleIncidence of Grade 3+ Treatment-related Toxicity, Measured by CTCAE v. 4 (Cohort 2)
    DescriptionAdverse events (AEs) are graded by using CTCAE 4.0. Possibly/probably/definitely related to protocol treatment AEs are considered.
    Time FrameFrom start of treatment up to 3 years.

    Outcome Measure Data

    Analysis Population Description
    Randomized and eligible patients who started protocol treatment.
    Arm/Group TitleCohort 2: Bevacizumab+PlaceboCohort 2: Bevacizumab+AMG 386
    Arm/Group DescriptionBevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
    Measure Participants5757
    Number [participants]
    21
    350%
    20
    34.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Safety Run-In, Cohort 2: Bevacizumab+AMG 386
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.85
    Comments
    MethodChi-squared
    Comments
    4. Secondary Outcome
    TitleOverall Survival (Cohort 2)
    DescriptionSurvival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. This analysis was planned to occur when all patients had been potentially followed for at least 6 months.
    Time FrameFrom randomization up to 3 years.

    Outcome Measure Data

    Analysis Population Description
    All randomized and eligible patients.
    Arm/Group TitleCohort 2: Bevacizumab+PlaceboCohort 2: Bevacizumab+AMG 386
    Arm/Group DescriptionBevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
    Measure Participants5857
    Median (95% Confidence Interval) [Months]
    11.5
    7.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Safety Run-In, Cohort 2: Bevacizumab+AMG 386
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.09
    Comments
    MethodLog Rank
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value1.46
    Confidence Interval (2-Sided) 95%
    0.95 to 2.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    TitleProgression-free Survival (Cohort 2)
    DescriptionProgression-free survival time is measured from randomization to the date of first progression or death or, otherwise, the last follow-up date on which the patient was reported alive. This analysis was planned to occur when all patients had been potentially followed for at least 6 months.
    Time FrameFrom randomization up to 3 years.

    Outcome Measure Data

    Analysis Population Description
    All randomized and eligible patients.
    Arm/Group TitleCohort 2: Bevacizumab+PlaceboCohort 2: Bevacizumab+AMG 386
    Arm/Group DescriptionBevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
    Measure Participants5857
    Number (95% Confidence Interval) [percentage of participants]
    4.8
    80%
    4.2
    7.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Safety Run-In, Cohort 2: Bevacizumab+AMG 386
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.04
    Comments
    MethodLog Rank
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value1.51
    Confidence Interval (2-Sided) 95%
    1.02 to 2.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    TitleRadiographic Response Rate (Cohort 2)
    DescriptionProportion of patients with best overall response of complete response (CR) or partial response (PR) recorded from the start of the treatment until disease progression/recurrence. Response determined by site-reported radiology review of MRI exams using Response Assessment in Neuro-Oncology Criteria (RANO) criteria. CR: Complete disappearance of all enhancing measurable disease (MD) + non-measurable disease (NMD) sustained >= 4 wks; No new lesions; Stable or improved non-enhancing (T2/FLAIR) lesions; Off corticosteroids (or on physiologic replacement doses only); Stable/improved clinically. PR: >= 50% decrease vs. baseline of sum of products of perpendicular diameters of all measurable enhancing lesions sustained >= 4 wks; No progression of NMD; No new lesions; Stable/improved non-enhancing (T2/FLAIR) lesions on <= dose of corticosteroids vs. baseline scan; Corticosteroid dose at evaluation scan <= baseline scan dose; Stable or improved clinically. NMD only cannot be a CR or PR.
    Time FrameFrom randomization up to 3 years.

    Outcome Measure Data

    Analysis Population Description
    All randomized and eligible patients.
    Arm/Group TitleCohort 2: Bevacizumab+PlaceboCohort 2: Bevacizumab+AMG 386
    Arm/Group DescriptionBevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
    Measure Participants5857
    Number (95% Confidence Interval) [percentage of participants]
    5.9
    98.3%
    4.2
    7.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Safety Run-In, Cohort 2: Bevacizumab+AMG 386
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.7
    Comments
    MethodChi-squared
    Comments
    7. Secondary Outcome
    TitlePercentage of Patients Requiring Dose Reduction/Interruption or Discontinuation in the First 2 and Subsequent Courses (Cohort 1)
    DescriptionFeasibility of trebananib weekly in combination with bevacizumab every 2 weeks, measured by the percentage of patients requiring dose reduction/interruption or discontinuation in the first 2 and subsequent courses (Cohort 1)
    Time FrameFrom randomization up to 3 years.

    Outcome Measure Data

    Analysis Population Description
    Eligible patients
    Arm/Group TitleSafety Run-In
    Arm/Group DescriptionBevacizumab every 2 weeks + AMG 386 weekly until disease progression.
    Measure Participants6
    In first 2 cycles
    6
    100%
    In first 6 cycles
    3
    50%
    In first 12 cycles
    5
    83.3%
    8. Other Pre-specified Outcome
    TitleTumor Genotype, Expression Profile, and Circulating Angiogenesis Biomarkers (Cohort 2)
    DescriptionBiomarker data has not yet been obtained and therefore this outcome measure cannot yet be reported.
    Time FrameFrom randomization to date of death or last followup. Statistical analysis occurs when tumor genotype, expression profile and circulating angiogenesis biomarkers have been determined from the tissue specimens.

    Outcome Measure Data

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

    Adverse Events

    Time Frame
    Adverse Event Reporting Description Randomized and eligible patients who started protocol treatment are included in the adverse event tables. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
    Arm/Group TitleCohort 1: Safety Run-InCohort 2: Bevacizumab+PlaceboCohort 2: Bevacizumab+AMG 386
    Arm/Group DescriptionBevacizumab every 2 weeks + AMG 386 weekly until disease progression.Bevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
    All Cause Mortality
    Cohort 1: Safety Run-InCohort 2: Bevacizumab+PlaceboCohort 2: Bevacizumab+AMG 386
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total/ (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Cohort 1: Safety Run-InCohort 2: Bevacizumab+PlaceboCohort 2: Bevacizumab+AMG 386
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total5/6 (83.3%) 22/57 (38.6%) 20/57 (35.1%)
    Cardiac disorders
    Ventricular fibrillation0/6 (0%) 0/57 (0%) 1/57 (1.8%)
    Endocrine disorders
    Hyperthyroidism0/6 (0%) 0/57 (0%) 1/57 (1.8%)
    Gastrointestinal disorders
    Retroperitoneal hemorrhage0/6 (0%) 0/57 (0%) 1/57 (1.8%)
    General disorders
    Edema limbs0/6 (0%) 1/57 (1.8%) 1/57 (1.8%)
    Flu like symptoms0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Gait disturbance0/6 (0%) 3/57 (5.3%) 0/57 (0%)
    Non-cardiac chest pain0/6 (0%) 0/57 (0%) 1/57 (1.8%)
    Infections and infestations
    Infections and infestations - Other0/6 (0%) 0/57 (0%) 1/57 (1.8%)
    Lung infection0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Meningitis0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Sepsis0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Skin infection1/6 (16.7%) 1/57 (1.8%) 1/57 (1.8%)
    Urinary tract infection2/6 (33.3%) 1/57 (1.8%) 1/57 (1.8%)
    Wound infection0/6 (0%) 0/57 (0%) 1/57 (1.8%)
    Injury, poisoning and procedural complications
    Fall0/6 (0%) 1/57 (1.8%) 1/57 (1.8%)
    Hip fracture1/6 (16.7%) 0/57 (0%) 0/57 (0%)
    Spinal fracture0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Wound dehiscence0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Investigations
    Aspartate aminotransferase increased1/6 (16.7%) 0/57 (0%) 0/57 (0%)
    Lymphocyte count decreased0/6 (0%) 0/57 (0%) 1/57 (1.8%)
    Platelet count decreased0/6 (0%) 0/57 (0%) 1/57 (1.8%)
    Metabolism and nutrition disorders
    Hyperglycemia1/6 (16.7%) 1/57 (1.8%) 1/57 (1.8%)
    Hyponatremia0/6 (0%) 3/57 (5.3%) 0/57 (0%)
    Metabolism and nutrition disorders - Other0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritis0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Generalized muscle weakness0/6 (0%) 2/57 (3.5%) 1/57 (1.8%)
    Muscle weakness lower limb0/6 (0%) 1/57 (1.8%) 2/57 (3.5%)
    Muscle weakness upper limb0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other1/6 (16.7%) 2/57 (3.5%) 3/57 (5.3%)
    Nervous system disorders
    Aphonia0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Ataxia0/6 (0%) 0/57 (0%) 1/57 (1.8%)
    Cerebrospinal fluid leakage0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Cognitive disturbance0/6 (0%) 2/57 (3.5%) 1/57 (1.8%)
    Depressed level of consciousness0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Dizziness0/6 (0%) 0/57 (0%) 1/57 (1.8%)
    Dysphasia0/6 (0%) 2/57 (3.5%) 0/57 (0%)
    Encephalopathy0/6 (0%) 2/57 (3.5%) 0/57 (0%)
    Headache0/6 (0%) 1/57 (1.8%) 1/57 (1.8%)
    Intracranial hemorrhage0/6 (0%) 1/57 (1.8%) 1/57 (1.8%)
    Memory impairment0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Nervous system disorders - Other0/6 (0%) 0/57 (0%) 2/57 (3.5%)
    Seizure2/6 (33.3%) 4/57 (7%) 4/57 (7%)
    Stroke0/6 (0%) 2/57 (3.5%) 1/57 (1.8%)
    Transient ischemic attacks0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Psychiatric disorders
    Confusion0/6 (0%) 2/57 (3.5%) 3/57 (5.3%)
    Delirium0/6 (0%) 1/57 (1.8%) 1/57 (1.8%)
    Renal and urinary disorders
    Acute kidney injury0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Pleural effusion0/6 (0%) 1/57 (1.8%) 0/57 (0%)
    Respiratory failure0/6 (0%) 0/57 (0%) 1/57 (1.8%)
    Vascular disorders
    Hypertension0/6 (0%) 1/57 (1.8%) 3/57 (5.3%)
    Thromboembolic event0/6 (0%) 1/57 (1.8%) 2/57 (3.5%)
    Other (Not Including Serious) Adverse Events
    Cohort 1: Safety Run-InCohort 2: Bevacizumab+PlaceboCohort 2: Bevacizumab+AMG 386
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total6/6 (100%) 57/57 (100%) 54/57 (94.7%)
    Blood and lymphatic system disorders
    Anemia3/6 (50%) 14/57 (24.6%) 9/57 (15.8%)
    Cardiac disorders
    Sinus tachycardia1/6 (16.7%) 1/57 (1.8%) 0/57 (0%)
    Ear and labyrinth disorders
    Hearing impaired1/6 (16.7%) 0/57 (0%) 2/57 (3.5%)
    Endocrine disorders
    Cushingoid1/6 (16.7%) 0/57 (0%) 2/57 (3.5%)
    Eye disorders
    Blurred vision0/6 (0%) 4/57 (7%) 7/57 (12.3%)
    Dry eye1/6 (16.7%) 1/57 (1.8%) 1/57 (1.8%)
    Eye disorders - Other0/6 (0%) 5/57 (8.8%) 9/57 (15.8%)
    Gastrointestinal disorders
    Abdominal pain0/6 (0%) 4/57 (7%) 5/57 (8.8%)
    Constipation3/6 (50%) 15/57 (26.3%) 6/57 (10.5%)
    Diarrhea2/6 (33.3%) 13/57 (22.8%) 8/57 (14%)
    Dry mouth0/6 (0%) 3/57 (5.3%) 1/57 (1.8%)
    Dyspepsia0/6 (0%) 6/57 (10.5%) 3/57 (5.3%)
    Dysphagia1/6 (16.7%) 1/57 (1.8%) 3/57 (5.3%)
    Fecal incontinence1/6 (16.7%) 2/57 (3.5%) 0/57 (0%)
    Gastrointestinal disorders - Other1/6 (16.7%) 3/57 (5.3%) 1/57 (1.8%)
    Mucositis oral1/6 (16.7%) 4/57 (7%) 4/57 (7%)
    Nausea2/6 (33.3%) 14/57 (24.6%) 8/57 (14%)
    Vomiting2/6 (33.3%) 11/57 (19.3%) 2/57 (3.5%)
    General disorders
    Chills0/6 (0%) 3/57 (5.3%) 0/57 (0%)
    Edema face0/6 (0%) 1/57 (1.8%) 4/57 (7%)
    Edema limbs2/6 (33.3%) 12/57 (21.1%) 12/57 (21.1%)
    Fatigue4/6 (66.7%) 38/57 (66.7%) 37/57 (64.9%)
    Fever1/6 (16.7%) 6/57 (10.5%) 0/57 (0%)
    Gait disturbance1/6 (16.7%) 13/57 (22.8%) 7/57 (12.3%)
    General disorders and administration site conditions - Other0/6 (0%) 4/57 (7%) 2/57 (3.5%)
    Injection site reaction1/6 (16.7%) 1/57 (1.8%) 1/57 (1.8%)
    Localized edema0/6 (0%) 4/57 (7%) 1/57 (1.8%)
    Malaise1/6 (16.7%) 1/57 (1.8%) 0/57 (0%)
    Non-cardiac chest pain1/6 (16.7%) 2/57 (3.5%) 2/57 (3.5%)
    Pain2/6 (33.3%) 8/57 (14%) 8/57 (14%)
    Infections and infestations
    Esophageal infection1/6 (16.7%) 0/57 (0%) 0/57 (0%)
    Soft tissue infection1/6 (16.7%) 0/57 (0%) 0/57 (0%)
    Upper respiratory infection0/6 (0%) 3/57 (5.3%) 3/57 (5.3%)
    Urinary tract infection1/6 (16.7%) 1/57 (1.8%) 4/57 (7%)
    Vaginal infection1/6 (16.7%) 0/57 (0%) 0/57 (0%)
    Injury, poisoning and procedural complications
    Bruising0/6 (0%) 4/57 (7%) 4/57 (7%)
    Fall2/6 (33.3%) 5/57 (8.8%) 9/57 (15.8%)
    Fracture1/6 (16.7%) 1/57 (1.8%) 1/57 (1.8%)
    Investigations
    Activated partial thromboplastin time prolonged0/6 (0%) 2/57 (3.5%) 3/57 (5.3%)
    Alanine aminotransferase increased3/6 (50%) 15/57 (26.3%) 9/57 (15.8%)
    Alkaline phosphatase increased2/6 (33.3%) 5/57 (8.8%) 4/57 (7%)
    Aspartate aminotransferase increased0/6 (0%) 9/57 (15.8%) 6/57 (10.5%)
    Blood bilirubin increased0/6 (0%) 3/57 (5.3%) 3/57 (5.3%)
    CPK increased1/6 (16.7%) 0/57 (0%) 0/57 (0%)
    Creatinine increased1/6 (16.7%) 1/57 (1.8%) 2/57 (3.5%)
    Investigations - Other1/6 (16.7%) 3/57 (5.3%) 3/57 (5.3%)
    Lymphocyte count decreased2/6 (33.3%) 17/57 (29.8%) 15/57 (26.3%)
    Neutrophil count decreased0/6 (0%) 6/57 (10.5%) 4/57 (7%)
    Platelet count decreased1/6 (16.7%) 10/57 (17.5%) 10/57 (17.5%)
    Weight gain1/6 (16.7%) 0/57 (0%) 3/57 (5.3%)
    Weight loss2/6 (33.3%) 6/57 (10.5%) 2/57 (3.5%)
    White blood cell decreased1/6 (16.7%) 11/57 (19.3%) 10/57 (17.5%)
    Metabolism and nutrition disorders
    Anorexia2/6 (33.3%) 10/57 (17.5%) 5/57 (8.8%)
    Dehydration1/6 (16.7%) 2/57 (3.5%) 3/57 (5.3%)
    Hyperglycemia2/6 (33.3%) 22/57 (38.6%) 16/57 (28.1%)
    Hyperkalemia0/6 (0%) 4/57 (7%) 2/57 (3.5%)
    Hypermagnesemia0/6 (0%) 3/57 (5.3%) 5/57 (8.8%)
    Hypernatremia1/6 (16.7%) 1/57 (1.8%) 2/57 (3.5%)
    Hypoalbuminemia2/6 (33.3%) 5/57 (8.8%) 5/57 (8.8%)
    Hypocalcemia2/6 (33.3%) 3/57 (5.3%) 5/57 (8.8%)
    Hypoglycemia1/6 (16.7%) 2/57 (3.5%) 2/57 (3.5%)
    Hypokalemia1/6 (16.7%) 8/57 (14%) 5/57 (8.8%)
    Hypomagnesemia1/6 (16.7%) 6/57 (10.5%) 4/57 (7%)
    Hyponatremia2/6 (33.3%) 9/57 (15.8%) 7/57 (12.3%)
    Hypophosphatemia1/6 (16.7%) 8/57 (14%) 5/57 (8.8%)
    Metabolism and nutrition disorders - Other0/6 (0%) 5/57 (8.8%) 1/57 (1.8%)
    Musculoskeletal and connective tissue disorders
    Arthralgia2/6 (33.3%) 11/57 (19.3%) 5/57 (8.8%)
    Arthritis1/6 (16.7%) 0/57 (0%) 2/57 (3.5%)
    Back pain2/6 (33.3%) 7/57 (12.3%) 2/57 (3.5%)
    Bone pain1/6 (16.7%) 2/57 (3.5%) 0/57 (0%)
    Flank pain1/6 (16.7%) 0/57 (0%) 0/57 (0%)
    Generalized muscle weakness3/6 (50%) 9/57 (15.8%) 10/57 (17.5%)
    Muscle weakness left-sided1/6 (16.7%) 12/57 (21.1%) 6/57 (10.5%)
    Muscle weakness lower limb1/6 (16.7%) 5/57 (8.8%) 8/57 (14%)
    Muscle weakness right-sided0/6 (0%) 3/57 (5.3%) 4/57 (7%)
    Muscle weakness upper limb1/6 (16.7%) 2/57 (3.5%) 1/57 (1.8%)
    Musculoskeletal and connective tissue disorder - Other0/6 (0%) 2/57 (3.5%) 3/57 (5.3%)
    Myalgia1/6 (16.7%) 3/57 (5.3%) 3/57 (5.3%)
    Neck pain1/6 (16.7%) 2/57 (3.5%) 1/57 (1.8%)
    Pain in extremity2/6 (33.3%) 9/57 (15.8%) 9/57 (15.8%)
    Nervous system disorders
    Amnesia1/6 (16.7%) 1/57 (1.8%) 2/57 (3.5%)
    Ataxia2/6 (33.3%) 5/57 (8.8%) 4/57 (7%)
    Cognitive disturbance0/6 (0%) 8/57 (14%) 2/57 (3.5%)
    Concentration impairment1/6 (16.7%) 0/57 (0%) 2/57 (3.5%)
    Depressed level of consciousness1/6 (16.7%) 2/57 (3.5%) 0/57 (0%)
    Dizziness2/6 (33.3%) 11/57 (19.3%) 11/57 (19.3%)
    Dysarthria0/6 (0%) 6/57 (10.5%) 6/57 (10.5%)
    Dysgeusia1/6 (16.7%) 0/57 (0%) 1/57 (1.8%)
    Dysphasia1/6 (16.7%) 10/57 (17.5%) 7/57 (12.3%)
    Facial muscle weakness2/6 (33.3%) 0/57 (0%) 0/57 (0%)
    Facial nerve disorder1/6 (16.7%) 0/57 (0%) 0/57 (0%)
    Headache2/6 (33.3%) 32/57 (56.1%) 19/57 (33.3%)
    Lethargy1/6 (16.7%) 1/57 (1.8%) 1/57 (1.8%)
    Memory impairment1/6 (16.7%) 11/57 (19.3%) 10/57 (17.5%)
    Nervous system disorders - Other1/6 (16.7%) 9/57 (15.8%) 7/57 (12.3%)
    Paresthesia1/6 (16.7%) 7/57 (12.3%) 8/57 (14%)
    Peripheral sensory neuropathy2/6 (33.3%) 5/57 (8.8%) 5/57 (8.8%)
    Seizure1/6 (16.7%) 11/57 (19.3%) 5/57 (8.8%)
    Somnolence1/6 (16.7%) 0/57 (0%) 1/57 (1.8%)
    Tremor0/6 (0%) 5/57 (8.8%) 3/57 (5.3%)
    Psychiatric disorders
    Agitation1/6 (16.7%) 1/57 (1.8%) 2/57 (3.5%)
    Anxiety0/6 (0%) 9/57 (15.8%) 4/57 (7%)
    Confusion3/6 (50%) 7/57 (12.3%) 6/57 (10.5%)
    Depression1/6 (16.7%) 9/57 (15.8%) 9/57 (15.8%)
    Insomnia3/6 (50%) 9/57 (15.8%) 11/57 (19.3%)
    Renal and urinary disorders
    Hematuria2/6 (33.3%) 5/57 (8.8%) 5/57 (8.8%)
    Proteinuria1/6 (16.7%) 9/57 (15.8%) 7/57 (12.3%)
    Urinary frequency2/6 (33.3%) 3/57 (5.3%) 4/57 (7%)
    Urinary incontinence3/6 (50%) 5/57 (8.8%) 4/57 (7%)
    Urinary retention1/6 (16.7%) 0/57 (0%) 0/57 (0%)
    Urinary urgency1/6 (16.7%) 1/57 (1.8%) 0/57 (0%)
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis1/6 (16.7%) 2/57 (3.5%) 1/57 (1.8%)
    Cough2/6 (33.3%) 12/57 (21.1%) 8/57 (14%)
    Dyspnea1/6 (16.7%) 7/57 (12.3%) 3/57 (5.3%)
    Epistaxis0/6 (0%) 7/57 (12.3%) 3/57 (5.3%)
    Hoarseness0/6 (0%) 6/57 (10.5%) 4/57 (7%)
    Laryngeal inflammation1/6 (16.7%) 1/57 (1.8%) 0/57 (0%)
    Nasal congestion0/6 (0%) 4/57 (7%) 0/57 (0%)
    Postnasal drip2/6 (33.3%) 1/57 (1.8%) 1/57 (1.8%)
    Productive cough2/6 (33.3%) 2/57 (3.5%) 1/57 (1.8%)
    Sore throat1/6 (16.7%) 4/57 (7%) 4/57 (7%)
    Skin and subcutaneous tissue disorders
    Alopecia2/6 (33.3%) 3/57 (5.3%) 3/57 (5.3%)
    Dry skin0/6 (0%) 1/57 (1.8%) 6/57 (10.5%)
    Periorbital edema1/6 (16.7%) 0/57 (0%) 1/57 (1.8%)
    Pruritus2/6 (33.3%) 1/57 (1.8%) 4/57 (7%)
    Purpura0/6 (0%) 3/57 (5.3%) 1/57 (1.8%)
    Rash acneiform0/6 (0%) 4/57 (7%) 4/57 (7%)
    Rash maculo-papular1/6 (16.7%) 5/57 (8.8%) 2/57 (3.5%)
    Skin and subcutaneous tissue disorders - Other0/6 (0%) 5/57 (8.8%) 3/57 (5.3%)
    Vascular disorders
    Hematoma2/6 (33.3%) 1/57 (1.8%) 1/57 (1.8%)
    Hypertension3/6 (50%) 24/57 (42.1%) 25/57 (43.9%)
    Thromboembolic event1/6 (16.7%) 2/57 (3.5%) 7/57 (12.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

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

    Results Point of Contact

    Name/TitleWendy Seiferheld, M.S.
    OrganizationNRG Oncology
    Phone
    Emailseiferheldw@nrgoncology.org
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01609790
    Other Study ID Numbers:
    • NCI-2012-01969
    • NCI-2012-01969
    • S13-00759
    • CDR0000734205
    • RTOG-1122
    • RTOG-1122
    • RTOG-1122
    • U10CA180868
    • U10CA021661
    First Posted:
    Jun 1, 2012
    Last Update Posted:
    Dec 22, 2021
    Last Verified:
    Dec 1, 2021