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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01648348
Other study ID # NCI-2012-01989
Secondary ID NCI-2012-01989CD
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date November 2012
Est. completion date April 15, 2017

Study information

Verified date April 2018
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This partially randomized phase I/II trial studies the side effects and the best dose of anti-endoglin monoclonal antibody TRC105 when given together with bevacizumab and to see how well they work in treating patients with glioblastoma multiforme that has come back. Monoclonal antibodies, such as anti-endoglin monoclonal antibody TRC105 and bevacizumab, may find tumor cells and help kill them. Giving anti-endoglin monoclonal antibody TRC105 together with bevacizumab may be an effective treatment for glioblastoma multiforme.


Description:

PRIMARY OBJECTIVES:

I. To establish a maximum tolerated dose (MTD) of TRC105 (anti-endoglin monoclonal antibody TRC105) combined with bevacizumab in this patient population. (Phase I) II. To assess the safety and adverse events of TRC105 in combination with bevacizumab in this patient population. (Phase II) III. To determine the efficacy of TRC105 in combination with bevacizumab in recurrent glioblastoma as measured by progression-free survival and compare it with the efficacy of bevacizumab alone in this patient population. (Phase II)

SECONDARY OBJECTIVES:

I. To assess the proportion of patients, who are progression free at 6 months, treated with TRC105 in combination with bevacizumab as compared to bevacizumab alone. (Phase II) II. To assess the overall survival of patients treated with TRC105 in combination with bevacizumab compared to bevacizumab alone. (Phase II) III. To compare the impact of the treatment on the patients quality of life (QOL) using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QLQ)-C15-Palliative Care (PAL) and QLQ-brain neoplasm (BN)20 Patient Questionnaires. (Phase II) IV. To estimate patient recommendations for study participation to others using the Was It Worth It (WIWI) Questionnaire. (Phase II)

TERTIARY OBJECTIVES:

I. To evaluate the pharmacokinetics of TRC105. (Phase I) II. To evaluate the immunogenicity of TRC105. (Phase I) III. To determine the relationship between tumor biomarkers, circulating biomarkers of vascular response and vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) single-nucleotide polymorphisms (SNPs) in predicting efficacy and/or toxicity of treatment. (Phase II) IV. To assess the utility of magnetic resonance imaging (MRI) imaging including apparent diffusion coefficient (ADC) as a predictor of response and survival. (Phase II) V. To assess the utility of dynamic contrast enhanced (DCE) MRI as a predictor of response to bevacizumab with or without TRC105. (Phase II)

OUTLINE: This is a phase I dose-escalation study of anti-endoglin monoclonal antibody TRC105, followed by a randomized phase II study.

Phase I (closed to accrual 1/14/14): Patients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 and 11 of course 1 and days 1 and 8 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Phase II: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive bevacizumab IV over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 and 11 of course 1 and days 1 and 8 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive bevacizumab as in arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

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


Recruitment information / eligibility

Status Completed
Enrollment 116
Est. completion date April 15, 2017
Est. primary completion date May 11, 2016
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Histological confirmation of grade 3 or 4 glioma, including astrocytoma, oligodendroglioma, and mixed gliomas, as determined by pre-registration central pathology review (Phase I)

- Histological confirmation of glioblastoma multiforme (grade 4 astrocytoma) as determined by pre-registration central pathology review; note: gliosarcomas and other grade 4 astrocytoma variants (e.g., giant cell) are eligible; glioblastoma (GBM) with oligodendroglial features are NOT PERMITTED in this study if they are 1p19q co-deleted; sites submitting GBM with oligodendroglial features will be asked to provide results of 1p/19q co-deletion status (Phase II)

- Evidence of tumor progression by MRI or computed tomography (CT) scan following radiation therapy or following the most recent anti-tumor therapy; note: patients who have had surgical treatment at recurrence are eligible if they had a resection with measurable or non-measurable residual disease on postoperative imaging or if there is imaging evidence of disease progression as compared to the first postoperative scan

- Measurable or evaluable disease by gadolinium MRI or contrast CT scan; note: patients who have had a gross total resection (GTR) are eligible on the basis of evaluable disease

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

- Absolute neutrophil count (ANC) >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- White blood cells (WBC) >= 3,000/mL

- Hemoglobin >= 10.0 g/dL; note: this level may be reached by transfusion

- Total bilirubin =< institutional upper limit of normal (ULN)

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2 x ULN

- Creatinine =< ULN

- Life expectancy >= 12 weeks

- Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only

- Urine protein creatinine (UPC) ratio < 1; note: urine protein must be screened by urine analysis for UPC ratio; for UPC ratio >= 1.0, 24-hour urine protein must be obtained and the level should be < 1,000 mg for registration

- Fixed or decreasing dose of corticosteroids (or no corticosteroids) >= 7 days prior to registration

- Calculated glomerular filtration rate (GFR) must be >= 60 ml/min; GFR will be calculated as needed per institutional guidelines

- Any number of prior chemotherapy regimens for recurrent disease (Phase I); =< 1 chemotherapy or other non-antiangiogenic regimen for recurrent disease (Phase II)

- Last dose of bevacizumab >= 2 weeks prior to registration (Phase I); note: for the phase II study only, prior exposure to bevacizumab is not allowed

- Surgery >= 4 weeks prior to registration

- Completion of radiation therapy >= 12 weeks prior to registration and prior chemotherapy >= 4 weeks prior to registration (>= 6 weeks from nitrosourea-containing regimens)

- Small molecular cell cycle inhibitors >= 2 weeks from registration

- Ability to provide informed written consent

- Ability to complete questionnaire(s) by themselves or with assistance

- Willing to return to enrolling institution for follow-up

- Willing to discontinue use of medications that inhibit platelet function >= 10 days prior to registration; aspirin at doses greater than 325 mg/day must be discontinued >= 10 days prior to registration and avoided through the study; note: nonsteroidal anti-inflammatory drug (NSAID) medications are recommended in place of aspirin; if NSAIDs or aspirin are used, histamine (H)-2 blockers and proton pump inhibitor (PPI) medications are recommended

- Willing to provide mandatory blood and tissue samples for correlative research purposes (Phase I and II)

Exclusion Criteria:

- Any of the following:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the duration of the study and for at least 6 months after treatment has ended

- Prior hypersensitivity to bevacizumab or toxicity requiring discontinuation of bevacizumab (Phase I)

- Any prior exposure to any VEGF or VEGF inhibitor including, but not limited to, bevacizumab, cediranib, vandetanib, sunitinib, pazopanib, aflibercept, or sorafenib (Phase II)

- Prior hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (Phase I and II)

- Prior hypersensitivity to triptan derivatives (Phase I and II)

- Other active malignancy =< 3 years prior to registration; exceptions: non-melanotic skin cancer or carcinoma-in-situ of the cervix; note: if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer

- Uncontrolled infection

- Immunocompromised patients or patients known to be human immunodeficiency virus (HIV) positive and currently receiving combination antiretroviral therapy; patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial

- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the prescribed regimens

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

- History of hypertensive crisis or hypertensive encephalopathy

- Clinically significant cardiovascular disease defined as follows:

- Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] > 160 mm Hg and/or diastolic blood pressure [DBP] > 90 mm Hg despite antihypertensive therapy)

- History of cerebrovascular accident (CVA) within 6 months

- Myocardial infarction or unstable angina within 6 months

- New York Heart Association classification II, III, or IV cardiovascular disease

- Serious and inadequately controlled cardiac arrhythmia

- Significant vascular disease (i.e., aortic aneurysm, history of aortic dissection)

- Clinically significant peripheral vascular disease

- Evidence or history of bleeding diathesis (greater than normal risk of bleeding, i.e., hereditary hemorrhagic telangiectasia type I or HHT-1) or coagulopathy in the absence of therapeutic anti-coagulation or any hemorrhage/bleeding event > grade 3 within 4 weeks prior to registration; note: patients with full-dose anticoagulants are eligible provided the patient has been on a stable dose for at least 2 weeks of low molecular weight heparin; therapeutic Coumadin and aspirin doses > 325 mg daily are not allowed

- Receiving any other investigational agent that would be considered as a treatment for the primary neoplasm

- Prior treatment with TRC105

- Serious or non-healing wound, active ulcer, or untreated bone fracture

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =< 6 months prior to registration

- History of invasive procedures defined as follows:

- Major surgical procedure, open biopsy, or significant traumatic injury =< 28 days prior to registration

- Anticipation of need for major surgical procedures during the study

- Core biopsy =< 7 days prior to registration

- History of significant vascular disease (i.e., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) within 6 months prior to registration

Study Design


Intervention

Biological:
Anti-Endoglin Chimeric Monoclonal Antibody TRC105
Given IV
Bevacizumab
Given IV
Other:
Laboratory Biomarker Analysis
Correlative studies
Pharmacological Study
Correlative studies
Quality-of-Life Assessment
Ancillary studies

Locations

Country Name City State
United States Bixby Medical Center Adrian Michigan
United States Hickman Cancer Center Adrian Michigan
United States Lehigh Valley Hospital-Cedar Crest Allentown Pennsylvania
United States Mary Greeley Medical Center Ames Iowa
United States McFarland Clinic PC-William R Bliss Cancer Center Ames Iowa
United States Saint Joseph Mercy Hospital Ann Arbor Michigan
United States Hematology Oncology Associates of Central New York-Auburn Auburn New York
United States University Medical Center Brackenridge Austin Texas
United States Eastern Maine Medical Center Bangor Maine
United States Bronson Battle Creek Battle Creek Michigan
United States Strecker Cancer Center-Belpre Belpre Ohio
United States Lehigh Valley Hospital - Muhlenberg Bethlehem Pennsylvania
United States Constantinou, Costas L MD (UIA Investigator) Bettendorf Iowa
United States Billings Clinic Cancer Center Billings Montana
United States Montana Cancer Consortium NCORP Billings Montana
United States Saint Vincent Healthcare Billings Montana
United States Illinois CancerCare-Bloomington Bloomington Illinois
United States Saint Joseph Medical Center Bloomington Illinois
United States Saint Alphonsus Cancer Care Center-Boise Boise Idaho
United States Parkland Health Center-Bonne Terre Bonne Terre Missouri
United States McFarland Clinic PC-Boone Boone Iowa
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Cancer Center Boston Massachusetts
United States Toledo Clinic Cancer Centers-Bowling Green Bowling Green Ohio
United States Bozeman Deaconess Hospital Bozeman Montana
United States Lafayette Family Cancer Center-EMMC Brewer Maine
United States Fairview Ridges Hospital Burnsville Minnesota
United States Saint James Community Hospital and Cancer Treatment Center Butte Montana
United States Cooper Hospital University Medical Center Camden New Jersey
United States Illinois CancerCare-Canton Canton Illinois
United States Saint Francis Medical Center Cape Girardeau Missouri
United States Southeast Cancer Center Cape Girardeau Missouri
United States Memorial Hospital of Carbondale Carbondale Illinois
United States Illinois CancerCare-Carthage Carthage Illinois
United States Rocky Mountain Oncology Casper Wyoming
United States Mercy Hospital Cedar Rapids Iowa
United States Oncology Associates at Mercy Medical Center Cedar Rapids Iowa
United States Centralia Oncology Clinic Centralia Illinois
United States Cancer Center of Kansas - Chanute Chanute Kansas
United States Massachusetts General Hospital Charlestown Massachusetts
United States University of Virginia Cancer Center Charlottesville Virginia
United States Northwestern University Chicago Illinois
United States Adena Regional Medical Center Chillicothe Ohio
United States Oncology Hematology Care Inc - Anderson Cincinnati Ohio
United States Oncology Hematology Care Inc-Blue Ash Cincinnati Ohio
United States Oncology Hematology Care Inc-Eden Park Cincinnati Ohio
United States Oncology Hematology Care Inc-Kenwood Cincinnati Ohio
United States Oncology Hematology Care Inc-Mercy West Cincinnati Ohio
United States Big Horn Basin Cancer Center Cody Wyoming
United States Billings Clinic-Cody Cody Wyoming
United States Kootenai Medical Center Coeur d'Alene Idaho
United States Columbus NCI Community Oncology Research Program Columbus Ohio
United States Columbus Oncology and Hematology Associates Inc Columbus Ohio
United States Doctors Hospital Columbus Ohio
United States Grant Medical Center Columbus Ohio
United States Mount Carmel Health Center West Columbus Ohio
United States Riverside Methodist Hospital Columbus Ohio
United States The Mark H Zangmeister Center Columbus Ohio
United States New Hampshire Oncology Hematology PA-Concord Concord New Hampshire
United States Mercy Hospital Coon Rapids Minnesota
United States Baptist Health Corbin Corbin Kentucky
United States Oncology Hematology Care Inc-Crestview Crestview Hills Kentucky
United States Michiana Hematology Oncology PC-Crown Point Crown Point Indiana
United States UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas
United States Good Samaritan Hospital - Dayton Dayton Ohio
United States Miami Valley Hospital Dayton Ohio
United States Samaritan North Health Center Dayton Ohio
United States Beaumont Hospital-Dearborn Dearborn Michigan
United States Cancer Care Center of Decatur Decatur Illinois
United States Decatur Memorial Hospital Decatur Illinois
United States Delaware Health Center-Grady Cancer Center Delaware Ohio
United States Delaware Radiation Oncology Delaware Ohio
United States Grady Memorial Hospital Delaware Ohio
United States Saint John Hospital and Medical Center Detroit Michigan
United States Cancer Center of Kansas - Dodge City Dodge City Kansas
United States Essentia Health Cancer Center Duluth Minnesota
United States Essentia Health Saint Mary's Medical Center Duluth Minnesota
United States Miller-Dwan Hospital Duluth Minnesota
United States Saint Luke's Hospital of Duluth Duluth Minnesota
United States Greenville Health System Cancer Institute-Easley Easley South Carolina
United States Hematology Oncology Associates of Central New York-East Syracuse East Syracuse New York
United States Fairview-Southdale Hospital Edina Minnesota
United States Crossroads Cancer Center Effingham Illinois
United States Cancer Center of Kansas - El Dorado El Dorado Kansas
United States Hardin Memorial Hospital Elizabethtown Kentucky
United States Elkhart Clinic Elkhart Indiana
United States Elkhart General Hospital Elkhart Indiana
United States Michiana Hematology Oncology PC-Elkhart Elkhart Indiana
United States Illinois CancerCare-Eureka Eureka Illinois
United States NorthShore University HealthSystem-Evanston Hospital Evanston Illinois
United States Oncology Hematology Care Inc-Healthplex Fairfield Ohio
United States Blanchard Valley Hospital Findlay Ohio
United States Genesys Hurley Cancer Institute Flint Michigan
United States Hurley Medical Center Flint Michigan
United States McFarland Clinic PC-Trinity Cancer Center Fort Dodge Iowa
United States Cancer Center of Kansas - Fort Scott Fort Scott Kansas
United States Atrium Medical Center-Middletown Regional Hospital Franklin Ohio
United States Fredericksburg Oncology Inc Fredericksburg Virginia
United States Unity Hospital Fridley Minnesota
United States Saint Jude Medical Center Fullerton California
United States Illinois CancerCare-Galesburg Galesburg Illinois
United States Western Illinois Cancer Treatment Center Galesburg Illinois
United States NorthShore University HealthSystem-Glenbrook Hospital Glenview Illinois
United States Wayne Memorial Hospital Goldsboro North Carolina
United States Altru Cancer Center Grand Forks North Dakota
United States Mercy Health Saint Mary's Grand Rapids Michigan
United States Spectrum Health at Butterworth Campus Grand Rapids Michigan
United States Benefis Healthcare- Sletten Cancer Institute Great Falls Montana
United States Greenville Health System Cancer Institute-Andrews Greenville South Carolina
United States Greenville Health System Cancer Institute-Butternut Greenville South Carolina
United States Greenville Health System Cancer Institute-Eastside Greenville South Carolina
United States Greenville Health System Cancer Institute-Faris Greenville South Carolina
United States Greenville Memorial Hospital Greenville South Carolina
United States Wayne Hospital Greenville Ohio
United States Greenwich Hospital Greenwich Connecticut
United States Greenville Health System Cancer Institute-Greer Greer South Carolina
United States PinnacleHealth Cancer Center-Community Campus Harrisburg Pennsylvania
United States Smilow Cancer Hospital Care Center at Saint Francis Hartford Connecticut
United States Saint Peter's Community Hospital Helena Montana
United States Hematology Oncology Associates of Illinois-Highland Park Highland Park Illinois
United States NorthShore University HealthSystem-Highland Park Hospital Highland Park Illinois
United States New Hampshire Oncology Hematology PA-Hooksett Hooksett New Hampshire
United States Hutchinson Area Health Care Hutchinson Minnesota
United States Cancer Center of Kansas-Independence Independence Kansas
United States Indiana University/Melvin and Bren Simon Cancer Center Indianapolis Indiana
United States University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa
United States Allegiance Health Jackson Michigan
United States Mayo Clinic in Florida Jacksonville Florida
United States McFarland Clinic PC-Jefferson Jefferson Iowa
United States Capital Region Medical Center-Goldschmidt Cancer Center Jefferson City Missouri
United States Borgess Medical Center Kalamazoo Michigan
United States Bronson Methodist Hospital Kalamazoo Michigan
United States West Michigan Cancer Center Kalamazoo Michigan
United States Kalispell Regional Medical Center Kalispell Montana
United States Presence Saint Mary's Hospital Kankakee Illinois
United States Kettering Medical Center Kettering Ohio
United States Illinois CancerCare-Kewanee Clinic Kewanee Illinois
United States Cancer Center of Kansas-Kingman Kingman Kansas
United States Kinston Medical Specialists PA Kinston North Carolina
United States Community Howard Regional Health Kokomo Indiana
United States Gundersen Lutheran Medical Center La Crosse Wisconsin
United States IU Health La Porte Hospital La Porte Indiana
United States LRGHealthcare-Lakes Region General Hospital Laconia New Hampshire
United States Fairfield Medical Center Lancaster Ohio
United States Sparrow Hospital Lansing Michigan
United States Lawrence Memorial Hospital Lawrence Kansas
United States Dartmouth Hitchcock Medical Center Lebanon New Hampshire
United States Beebe Medical Center Lewes Delaware
United States Baptist Health Lexington Lexington Kentucky
United States Cancer Center of Kansas-Liberal Liberal Kansas
United States NorthShore Hematology Oncology-Libertyville Libertyville Illinois
United States Lima Memorial Hospital Lima Ohio
United States University of Arkansas for Medical Sciences Little Rock Arkansas
United States Saint Mary Mercy Hospital Livonia Michigan
United States Illinois CancerCare-Macomb Macomb Illinois
United States University of Wisconsin Hospital and Clinics Madison Wisconsin
United States Baptist Health Madisonville/Merle Mahr Cancer Center Madisonville Kentucky
United States Cancer Center of Kansas-Manhattan Manhattan Kansas
United States Minnesota Oncology Hematology PA-Maplewood Maplewood Minnesota
United States Saint John's Hospital - Healtheast Maplewood Minnesota
United States Marietta Memorial Hospital Marietta Ohio
United States OneHealth Marion General Hospital Marion Ohio
United States McFarland Clinic PC-Marshalltown Marshalltown Iowa
United States Toledo Clinic Cancer Centers-Maumee Maumee Ohio
United States Toledo Radiation Oncology at Northwest Ohio Onocolgy Center Maumee Ohio
United States Cancer Center of Kansas - McPherson McPherson Kansas
United States Community Memorial Hospital Menomonee Falls Wisconsin
United States Mount Sinai Medical Center Miami Beach Florida
United States Froedtert and the Medical College of Wisconsin Milwaukee Wisconsin
United States Abbott-Northwestern Hospital Minneapolis Minnesota
United States Health Partners Inc Minneapolis Minnesota
United States Hennepin County Medical Center Minneapolis Minnesota
United States Memorial Regional Cancer Center Day Road Mishawaka Indiana
United States Michiana Hematology Oncology PC-Mishawaka Mishawaka Indiana
United States Saint Joseph Regional Medical Center-Mishawaka Mishawaka Indiana
United States Community Medical Hospital Missoula Montana
United States Saint Patrick Hospital - Community Hospital Missoula Montana
United States Garneau, Stewart C MD (UIA Investigator) Moline Illinois
United States Spector, David MD (UIA Investigator) Moline Illinois
United States Trinity Medical Center Moline Illinois
United States Mercy Memorial Hospital Monroe Michigan
United States Toledo Clinic Cancer Centers-Monroe Monroe Michigan
United States Knox Community Hospital Mount Vernon Ohio
United States ProHealth D N Greenwald Center Mukwonago Wisconsin
United States Mercy Health Mercy Campus Muskegon Michigan
United States Cancer Center of Western Wisconsin New Richmond Wisconsin
United States New Ulm Medical Center New Ulm Minnesota
United States Memorial Sloan-Kettering Cancer Center New York New York
United States Mount Sinai Hospital New York New York
United States Christiana Care Health System-Christiana Hospital Newark Delaware
United States Christiana Gynecologic Oncology LLC Newark Delaware
United States Delaware Clinical and Laboratory Physicians PA Newark Delaware
United States Helen F Graham Cancer Center Newark Delaware
United States Licking Memorial Hospital Newark Ohio
United States Medical Oncology Hematology Consultants PA Newark Delaware
United States Newark Radiation Oncology Newark Ohio
United States Regional Hematology and Oncology PA Newark Delaware
United States Cancer Center of Kansas - Newton Newton Kansas
United States Illinois Cancer Specialists-Niles Niles Illinois
United States Lakeland Community Hospital Niles Michigan
United States ProHealth Oconomowoc Memorial Hospital Oconomowoc Wisconsin
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States University of Nebraska Medical Center Omaha Nebraska
United States Saint Joseph Hospital - Orange Orange California
United States Saint Charles Hospital Oregon Ohio
United States Toledo Clinic Cancer Centers-Oregon Oregon Ohio
United States Florida Hospital Orlando Orlando Florida
United States Illinois CancerCare-Ottawa Clinic Ottawa Illinois
United States Radiation Oncology of Northern Illinois Ottawa Illinois
United States Baptist Health Paducah Paducah Kentucky
United States Cancer Center of Kansas - Parsons Parsons Kansas
United States Illinois CancerCare-Pekin Pekin Illinois
United States OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center Pekin Illinois
United States Illinois CancerCare-Peoria Peoria Illinois
United States Methodist Medical Center of Illinois Peoria Illinois
United States OSF Saint Francis Medical Center Peoria Illinois
United States OSF Saint Francis Radiation Oncology at Peoria Cancer Center Peoria Illinois
United States Illinois CancerCare-Peru Peru Illinois
United States Valley Radiation Oncology Peru Illinois
United States Michiana Hematology Oncology PC-Plymouth Plymouth Indiana
United States Saint Joseph Mercy Oakland Pontiac Michigan
United States Lake Huron Medical Center Port Huron Michigan
United States Southern Ohio Medical Center Portsmouth Ohio
United States Kootenai Cancer Center Post Falls Idaho
United States Cancer Center of Kansas - Pratt Pratt Kansas
United States Illinois CancerCare-Princeton Princeton Illinois
United States Rapid City Regional Hospital Rapid City South Dakota
United States Spectrum Health Reed City Hospital Reed City Michigan
United States Beebe Health Campus Rehoboth Beach Delaware
United States Reid Health Richmond Indiana
United States North Memorial Medical Health Center Robbinsdale Minnesota
United States Mayo Clinic Rochester Minnesota
United States Saint Mary's of Michigan Saginaw Michigan
United States Coborn Cancer Center at Saint Cloud Hospital Saint Cloud Minnesota
United States Saint Cloud Hospital Saint Cloud Minnesota
United States Lakeland Hospital Saint Joseph Michigan
United States Marie Yeager Cancer Center Saint Joseph Michigan
United States Missouri Baptist Medical Center Saint Louis Missouri
United States Washington University School of Medicine Saint Louis Missouri
United States Metro Minnesota Community Oncology Research Consortium Saint Louis Park Minnesota
United States Park Nicollet Clinic - Saint Louis Park Saint Louis Park Minnesota
United States Regions Hospital Saint Paul Minnesota
United States United Hospital Saint Paul Minnesota
United States Sainte Genevieve County Memorial Hospital Sainte Genevieve Missouri
United States Cancer Center of Kansas - Salina Salina Kansas
United States Huntsman Cancer Institute/University of Utah Salt Lake City Utah
United States Sharp Memorial Hospital San Diego California
United States UCSF Medical Center-Mount Zion San Francisco California
United States UCSF Medical Center-Parnassus San Francisco California
United States Kootenai Cancer Clinic Sandpoint Idaho
United States Maine Center for Cancer Medicine-Scarborough Scarborough Maine
United States Nanticoke Memorial Hospital Seaford Delaware
United States Greenville Health System Cancer Institute-Seneca Seneca South Carolina
United States Saint Francis Regional Medical Center Shakopee Minnesota
United States Welch Cancer Center Sheridan Wyoming
United States Mercy Medical Center-Sioux City Sioux City Iowa
United States Saint Luke's Regional Medical Center Sioux City Iowa
United States Siouxland Regional Cancer Center Sioux City Iowa
United States Hematology Oncology Associates of Illinois - Skokie Skokie Illinois
United States Memorial Hospital of South Bend South Bend Indiana
United States Michiana Hematology Oncology PC-South Bend South Bend Indiana
United States Northern Indiana Cancer Research Consortium South Bend Indiana
United States South Bend Clinic South Bend Indiana
United States Greenville Health System Cancer Institute-Spartanburg Spartanburg South Carolina
United States Central Illinois Hematology Oncology Center Springfield Illinois
United States Memorial Medical Center Springfield Illinois
United States Southern Illinois University School of Medicine Springfield Illinois
United States Springfield Clinic Springfield Illinois
United States Springfield Regional Medical Center Springfield Ohio
United States Stamford Hospital/Bennett Cancer Center Stamford Connecticut
United States Lakeview Hospital Stillwater Minnesota
United States Missouri Baptist Sullivan Hospital Sullivan Missouri
United States Missouri Baptist Outpatient Center-Sunset Hills Sunset Hills Missouri
United States Cancer Care Specialists of Illinois-Swansea Swansea Illinois
United States Flower Hospital Sylvania Ohio
United States Hematology Oncology Associates of Central New York-Onondaga Hill Syracuse New York
United States State University of New York Upstate Medical University Syracuse New York
United States Mercy Hospital of Tiffin Tiffin Ohio
United States Mercy Saint Anne Hospital Toledo Ohio
United States Saint Vincent Mercy Medical Center Toledo Ohio
United States Toledo Clinic Cancer Centers-Toledo Toledo Ohio
United States Toledo Community Hospital Oncology Program CCOP Toledo Ohio
United States University of Toledo Toledo Ohio
United States Munson Medical Center Traverse City Michigan
United States Upper Valley Medical Center Troy Ohio
United States Oklahoma Cancer Specialists and Research Institute-Tulsa Tulsa Oklahoma
United States MD Anderson Cancer Center at Cooper-Voorhees Voorhees New Jersey
United States Ridgeview Medical Center Waconia Minnesota
United States Saint John Macomb-Oakland Hospital Warren Michigan
United States Northwestern Medicine Cancer Center Warrenville Warrenville Illinois
United States ProHealth Waukesha Memorial Hospital Waukesha Wisconsin
United States Fulton County Health Center Wauseon Ohio
United States Cancer Center of Kansas - Wellington Wellington Kansas
United States Reading Hospital West Reading Pennsylvania
United States Saint Ann's Hospital Westerville Ohio
United States Michiana Hematology Oncology PC-Westville Westville Indiana
United States Associates In Womens Health Wichita Kansas
United States Cancer Center of Kansas - Wichita Wichita Kansas
United States Cancer Center of Kansas-Wichita Medical Arts Tower Wichita Kansas
United States Via Christi Regional Medical Center Wichita Kansas
United States Wichita NCI Community Oncology Research Program Wichita Kansas
United States Rice Memorial Hospital Willmar Minnesota
United States Christiana Care Health System-Wilmington Hospital Wilmington Delaware
United States Cancer Center of Kansas - Winfield Winfield Kansas
United States Wake Forest University Health Sciences Winston-Salem North Carolina
United States Minnesota Oncology Hematology PA-Woodbury Woodbury Minnesota
United States Ann Arbor Hematology -Oncology Associates Ypsilanti Michigan
United States Genesis Healthcare System Cancer Care Center Zanesville Ohio

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Change in DCE-MRI Utility Associations between the change of DCE-MRI and PFS6 will be assessed using two-sample t-test. Baseline to up to 2 years
Other Change in MRI ADC Utility MRI ADC histogram metrics such as overall ADC, mean ADC of lower curve, percentage of ADC in lower curve, and skewness at baseline and change from baseline to the first follow-up MRI will be analyzed for association with progression free and overall survival. Kaplan-Meier survival curves, logrank and Cox regression tests will be used to estimate and compare the equality of the overall survival and progression-time distributions of patient subsets defined by the ADC histogram metrics. Baseline to up to 2 years
Other Changes in Tumor and Circulating Biomarkers Binary endpoints and categorical endpoints will be compared using Chi-Squared or Fisher's Exact tests between treatment groups. Continuous endpoints will be analyzed using change-from-baseline measures and compared using t-tests between treatment groups and time-points. Cox proportional hazards regression will be used to determine if there are differences in PFS and OS between the treatment groups after correcting for each biomarker in conjunction with standard clinical variables. Baseline to up to 2 years
Primary Maximum Tolerated Dose (MTD) (Phase I) as Measured by the Number of Participants With Dose Limiting Toxicities MTD for this study will be defined as the highest safely tolerated dose level where at most 1 out of 6 patients experience dose-limiting toxicity (DLT) with the next higher dose having at least 2 patients out of a maximum of 6 patients experience DLT. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. The number of DLT's will be reported here. 28 days
Primary Progression-free Survival (PFS) (Phase II) Progression Free Survival time is defined as the time from study randomization to documentation of disease progression. Patients who die without documentation of progression will be considered to have had tumor progression at the time of death. Patients who fail to return for evaluation after beginning therapy will be censored for progression on the last day of therapy or date last known to be alive, whichever is later. Patients who are still alive and have not progressed will be censored for progression at the time of the last tumor assessment. The time-to-progression distribution will be estimated using the Kaplan-Meier method. The time from study randomization to documentation of disease progression, assessed up to 2 years
Secondary Overall Toxicity Rate for Grade 3 or Higher Adverse Events Considered at Least Possibly Related to Treatment (Phase II) The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment will be compared using a Fisher's Exact test between the 2 treatment groups. Up to 2 years
Secondary Overall Survival (Phase II) Survival time is defined to be the length of time from start of study therapy to death due to any cause. All patients meeting the eligibility criteria that have signed a consent form and begun treatment will be considered evaluable for estimation of the survival distribution. The distribution of overall survival for both groups of the study will be estimated using the Kaplan-Meier method, and be compared using log-rank tests. The time from start of study therapy to death due to any cause, assessed up to 2 years
Secondary Progression Free Survival at 6 Months (PFS6) (Phase II) as Measured by the Percentage of Participants With Progression Free Survival at 6 Months PFS6 is defined as the time from start of study therapy to the date of first observation of disease progression or death due to any cause (whichever comes first). The medians and confidence intervals given are the Kaplan-Meier estimates. The time from study randomization to documentation of disease progression, assessed at 6 months
Secondary Quality of Life (QOL) as Assessed by the EORTC QLQ-C15-PAL Questionnaire [Item 15: Global Health Status/Quality of Life] (Phase II) Quality of Life (QOL) as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL questionnaire, as measured by the change from baseline to the end of cycle 2 (4 weeks) in the EORTC QLQ-C15-PAL item 15, Global health status/quality of life, score. The assessment was scored using EORTC's scoring algorithms. The score range is from 0-100 (0 corresponding to worst outcome; 100 corresponding to best outcome). Range of the change in scores from baseline to cycle 2 (4 weeks) is (-100,100). The mean change in score and 95% confidence interval of the change from baseline to the end of cycle 2 (4 weeks) are reported below. Baseline and 4 weeks
Secondary QOL Assessed by EORTC-QLQ-BN20 Patient Questionnaire [Items 1-20] (Phase II) QOL assessed by EORTC-QLQ-BN20 Patient Questionnaire (Brain cancer module), as measured by the change from baseline to the end of cycle 2 (4 weeks) in the EORTC QLQ-BN20 Items 1-20 are used to score the following 11 symptom scales: Future uncertainty (Items 1-3,5), Visual disorder (Items 6-8), Motor dysfunction (Items 10,15, 19), Communication deficit (Items 11-13), Headaches (Item 4), Seizures (Item 9), Drowsiness (Item 14), Itchy Skin (Item 17), Hair Loss (Item 16), Weakness of legs (Item 18), and Bladder control (Item 20). The assessment was scored using EORTC's scoring algorithms. The score range for each of the 11 symptom scales is from 0-100 (0 corresponding to not severe;100 corresponding to most severe). Range of changes in scores from baseline to cycle 2 (4 weeks) is (-100,100). The mean change in score and 95% confidence interval of each symptom scale are reported below. Baseline and 4 weeks
Secondary QOL Assessed by WIWI Questionnaire (Phase II) Quality of life (QOL) assessed by Was it worth it? (WIWI) questionnaire, as measured by the percentage of patients answering yes to the question "Was it worthwhile for you to participate in this research study?" Up to 4 weeks
See also
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