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A Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma (ReACT)

This study is currently recruiting participants.
Verified May 2013 by Celldex Therapeutics
Sponsor:
Information provided by (Responsible Party):
Celldex Therapeutics
ClinicalTrials.gov Identifier:
NCT01498328
First received: December 21, 2011
Last updated: May 7, 2013
Last verified: May 2013
History of Changes
  Purpose

The purpose of this research study is to find out whether adding an experimental vaccine called rindopepimut (also known as CDX-110) to the commonly used drug bevacizumab can improve progression free survival (slowing the growth of tumors) of patients with relapsed EGFRvIII positive glioblastoma.


Condition Intervention Phase
Glioblastoma
Small Cell Glioblastoma
Giant Cell Glioblastoma
Gliosarcoma
Glioblastoma With Oligodendroglial Component
Recurrent Glioblastoma
Relapsed Glioblastoma
 Drug: Bevacizumab
Drug: Rindopepimut (CDX-110) with GM-CSF
Drug: KLH
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma

Resource links provided by NLM:

MedlinePlus related topics: Brain Cancer Cancer
U.S. FDA Resources

Further study details as provided by Celldex Therapeutics:

Primary Outcome Measures:
  • Progression-free survival rate [ Time Frame: 6 months post-Day 1 ] [ Designated as safety issue: No ]
    Evaluate the antitumor activity of rindopepimut in adult patients with relapsed glioblastoma, as measured by the progression-free survival rate at 6 months post-Day 1 (PFS 6).


Secondary Outcome Measures:
  • Safety and Tolerability [ Time Frame: Until 28 days or initiation of other anti-cancer treatment, whichever is first ] [ Designated as safety issue: No ]
    Safety and tolerability will be evaluated by comparing the treatment regimens in regards to vital sign measurements, physical and neurological examinations, adverse events reporting, and Karnofsky performance status

  • Anti-tumor activity [ Time Frame: During treatment and every 8 weeks through follow up ] [ Designated as safety issue: No ]
    Evaluated by comparing the treatment regimens for anti-tumor activity, including objective response rate, overall progression free survival, and overall survival (OS).

  • EGFRvIII-specific immune response [ Time Frame: Several times during the first month of treatment and then approximately every 8 weeks until treatment is stopped. ] [ Designated as safety issue: No ]
    Characterize the EGFRvIII specific immune response to rindopepimut.


Estimated Enrollment: 95
Study Start Date: December 2011
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1a: Bevacizumab Naïve with Bevacizumab + rindopepimut.
About half of the patients who have never received treatment with bevacizumab will receive rindopepimut/GM-CSF in a blinded fashion in combination with bevacizumab.
 Drug: Bevacizumab
A vascular endothelial growth factor (VEGF)-specific humanized monoclonal antibody angiogenesis inhibitor. Infusions of 10 mg/kg of bevacizumab will begin on day 1 and will be administered every two weeks until progression of disease or intolerance during the treatment period.
Other Name: Avastin
Drug: Rindopepimut (CDX-110) with GM-CSF
Rindopepimut/GM-CSF will initially be given three times, two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8 mL containing approximately 500 mcg CDX-110 and 150 mcg GM-CSF.
Experimental: Group 1b: Bevacizumab Naïve with Bevacizumab + KLH control
About half of the patients who have never received treatment with bevacizumab will receive KLH in a blinded fashion in combination with bevacizumab.
 Drug: Bevacizumab
A vascular endothelial growth factor (VEGF)-specific humanized monoclonal antibody angiogenesis inhibitor. Infusions of 10 mg/kg of bevacizumab will begin on day 1 and will be administered every two weeks until progression of disease or intolerance during the treatment period.
Other Name: Avastin
Drug: KLH
KLH will initially be given three times, two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8 mL containing approximately 100 mcg of KLH.
Experimental: Group 2: Refractory to Bevacizumab
Patients with progressive disease while currently on or within two months after discontinuing bevacizumab will be administered rindopepimut/GM-CSF while continuing (or restarting if they had stopped bevacizumab).
 Drug: Bevacizumab
A vascular endothelial growth factor (VEGF)-specific humanized monoclonal antibody angiogenesis inhibitor. Infusions of 10 mg/kg of bevacizumab will begin on day 1 and will be administered every two weeks until progression of disease or intolerance during the treatment period.
Other Name: Avastin
Drug: Rindopepimut (CDX-110) with GM-CSF
Rindopepimut/GM-CSF will initially be given three times, two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8 mL containing approximately 500 mcg CDX-110 and 150 mcg GM-CSF.

Detailed Description:

This Phase II study will enroll patients into two groups. Group 1 are patients who have never been treated with bevacizumab. These patients will be randomly assigned to receive either rindopepimut/GM-CSF or KLH, each along with bevacizumab. Treatment assignment for Group 1 will be blinded. Group 2 patients are those who are refractory to bevacizumab (experienced recurrence or progression of glioblastoma while on bevacizumab). These patients will all receive rindopepimut/GM-CSF along with bevacizumab. Patients will be treated until disease progression or intolerance and all patients will be followed for survival. Patients may be treated with other therapies that are not part of the study after discontinuing treatment with the study vaccine.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Among other criteria, patients must meet the following conditions to be eligible for the study:

  1. Age ≥18 years of age.
  2. Histologic diagnosis of glioblastoma (WHO Grade IV).
  3. Previous treatment for glioblastoma must include surgery,conventional radiation therapy and temozolomide (TMZ).
  4. First or second relapse of de novo glioblastoma.
  5. Screening MRI must be obtained at least 4 weeks after any salvage surgery, and at least 12 weeks after radiation therapy.
  6. KPS of ≥ 70%.
  7. Life expectancy > 12 weeks.
  8. Documented EGFRvIII positive tumor status by a Sponsor designated laboratory.
  9. If applicable, systemic corticosteroid therapy must be at a dose of ≤ 4 mg of dexamethasone or equivalent per day during the week prior to Day 1.
  10. Evaluable disease

Exclusion Criteria:

Among other criteria, patients who meet the following conditions are NOT eligible for the study:

  1. Subjects unable to undergo an MRI with contrast.
  2. History, presence, or suspicion of metastatic disease
  3. Prior receipt of vaccination against EGFRvIII.
  4. Any known contraindications to receipt of study drugs, including known allergy or hypersensitivity to keyhole limpet hemocyanin (KLH), GM-CSF (sargramostim; LEUKINE®), polysorbate 80 or yeast derived products, or a history of anaphylactic reactions to shellfish proteins.
  5. Use of non-protein based investigational therapy within 14 days prior to Day 1 or use of antibody-based investigational therapy within 28 days prior to Day 1.
  6. Clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment
  7. Evidence of recent hemorrhage on screening MRI of the brain
  8. Evidence of current drug or alcohol abuse.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01498328

Contacts
Contact: Celldex Therapeutics Info@celldextherapeutics.com

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Thiru B Pillay, RN     205-934-1813     thiru@uab.edu    
Contact: Shirley Gibbs     205-975-0447     sgibbs@uab.edu    
Principal Investigator: Louis B Nabors, MD            
United States, Arizona
St. Joseph's Hospital and Medical Center / Barrow Neurological Institute Recruiting
Phoenix, Arizona, United States, 85013
Contact: Andrea E Ralph, RN         andrea.ralph@dignityhealth.org    
Principal Investigator: Lynn S Ashby, MD            
United States, California
University of Southern California (USC) Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90089
Contact: Aida Lozada, MA     323-865-3980     lozada@usc.edu    
Contact: Sandy Leong, RN     323-442-7532     sandyleo@usc.edu    
Principal Investigator: Rose K Lai, MD            
UC Irvine Chao Family Comprehensive Cancer Center Recruiting
Orange, California, United States, 92868
Contact: Christina Siwak, Ph.D     714-456-8549     csiwak@uci.edu    
Contact: Daniela Bota, M.D., Ph.D     714-456-7214        
Principal Investigator: Daniela Bota, M.D., Ph.D            
Stanford Cancer Institute, Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Sophie N Bertrand     650-723-4467     sophieb@stanford.edu    
Contact: Cathy Recht, RN     650-723-6095        
Principal Investigator: Gordon Li, MD            
United States, Colorado
University of Colorado, Denver Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Monica Robischon, RN, BSN     720-848-0661     Monica.robischon@ucdenver.edu    
Principal Investigator: Denise Damek, MD            
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Contact: Jennifer West, RN, BSN, CCRP     352-273-7981     Jennifer.West@Neurosurgery.ufl.edu    
Contact: Erin M Dunbar, MD     352-273-9000     edunbar@neurosurgery.ufl.edu    
Principal Investigator: Erin M Dunbar, MD            
United States, Georgia
Atlanta Cancer Care Recruiting
Atlanta, Georgia, United States, 30342
Contact: Jennifer Keller, BSN     770-851-2359     jkeller@atlantacancercare.com    
Contact: Julie F Carney, RN, BSN     770-777-1315     jcarney@atlantacancercare.com    
Principal Investigator: Ronald G Steis, MD            
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637-1470
Contact: Christina Amidei, RN PhD     773-834-0323     camidei1@bsd.uchicago.edu    
Contact: Crista Brawley, PhD     1-773-702-0316        
Principal Investigator: Maciej Lesniak, MD            
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Amanda Begley, R.N. , B.S.     312-563-2713     Amanda_Begley@Rush.edu    
Contact: Suzanne Matney, R.N.     312-942-2388        
Principal Investigator: Nina Paleologos, MD            
NorthShore University Health System Recruiting
Evanston, Illinois, United States, 60201
Contact: Ryan Merrell, MD     847-570-2025     NeuroOncResearch@northshore.org    
Contact: Pat Lada, RN     847-570-2025     NeuroOncResearch@northshore.org    
Principal Investigator: Ryan Merrell, MD            
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: David A Reardon, MD     617-632-2166     David_Reardon@DFCI.Harvard.edu    
Contact: Debra LaFrankie, RN, OCN     617-632-6327        
Principal Investigator: David A Reardon, MD            
United States, Michigan
Sparrow Cancer Center Recruiting
Lansing, Michigan, United States, 48912
Contact: Vicki Gilreath, RN, OCN     517-364-2811     Vicki.Gilreath@sparrow.org    
Contact: Harsha Trivedi, PhD, RN     517-364-3712        
Principal Investigator: Gordan Srkalovic, MD, PhD            
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Lisa Ochsner     314-286-2585     lochsner@dom.wustl.edu    
Principal Investigator: David Tran, MD, PhD            
United States, Nevada
S. Nevada Cancer Research Foundation Withdrawn
Las Vegas, Nevada, United States, 89106
United States, New York
The Long Island Brain Tumor Center at Neurology Surgery, P.C. Recruiting
Commack, New York, United States, 11725
Contact: R. Kimberly Prabhu, MA, CCRP     516-478-0010     kprabhu@nspc.com    
Contact: Kerry McConie, RN, OCN     516-478-0010     kmcconie@nspc.com    
Principal Investigator: J. Paul Duic, MD            
University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Contact: Jennifer Serventi, PA-C     585-276-3971     jennifer_serventi@urmc.rochester.edu    
Contact: Nimish Mohile, MD     585-275-5863        
Principal Investigator: Nimish Mohile, MD            
United States, North Carolina
The Preston Robert Tisch Brain Tumor Center; Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Annick DesJardins, MD     919-681-3824        
Contact: Susan Boulton, RN, BSN     919-668-0896     boult001@mc.duke.edu    
Principal Investigator: Annick DesJardins, MD            
Wake Forest Baptist Health Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Jennifer MacLean, BS, RN, OCN     336-713-3539     jemaclea@wakehealth.edu    
Contact: Glenn Lesser, MD     336-713-5440     glesser@wakehealth.edu    
Principal Investigator: Glenn Lesser, MD            
United States, Ohio
University of Cincinnati Cancer Institute Recruiting
Cincinnati, Ohio, United States, 45267
Contact: University of Cincinnati Cancer Institute     513-584-7698        
Principal Investigator: Rekha Chaudhary, MD            
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Andrew Sloan, MD     216-844-6054     andrew.sloan@uhhospitals.org    
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: David Peereboom, MD     216-445-6068     Peerebd@ccf.org    
Contact: Cathy Brewer, RN     216-444-7937        
Principal Investigator: David Peereboom, MD            
United States, Oregon
Legacy Research Institute Recruiting
Portland, Oregon, United States, 97232
Contact: Susan Staat, RN     503-413-8330     sstaat@lhs.org    
Contact: Amy Reiter, RN     503-413-7094     areiter@lhs.org    
Principal Investigator: Jefferson Chen, MD            
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Lisa D. Pritchett or Eileen Maloney-Wilensky, MSN,RN, MHA and MSN, CRNP     215-615-4597     lisa.pritchett@uphs.penn.edu    
Contact: Suzanne Frangos, RN, CNRN     215-285-2885     frangoss@uphs.upenn.edu    
Principal Investigator: James Schuster, MD            
United States, Rhode Island
Rhode Island Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Heinrich Elinzano, MD     401-444-4673        
Principal Investigator: Heinrich Elinzano, MD            
United States, Texas
Texas Oncology Midtown Recruiting
Austin, Texas, United States, 78705
Contact: Sheree Adams     512-421-4183     sheree.adams@usoncology.com    
Contact: Marlena Griffin, BSc     512-421-4100     marlena.griffin@usoncology.com    
Principal Investigator: Morris D Groves, MD            
Baylor Research Institute Recruiting
Dallas, Texas, United States, 75246
Contact: Grace Rivera     214-818-8472     Grace.Rivera@BaylorHealth.edu    
Contact: Valerie Clark     214-820-6168        
Principal Investigator: Karen Fink, MD PhD            
United States, Utah
Utah Cancer Specialists Recruiting
Salt Lake City, Utah, United States, 84116
Contact: Nitin Chandramouli, MD     801-269-0231        
Contact: Johnny Walker     801-281-6864     research@utahcancer.com    
Principal Investigator: Nitin Chandramouli, MD            
United States, Washington
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98195
Contact: Fereshteh Assadian, RN     206-288-6693     fassadia@uw.edu    
Contact     206-685-5597        
Principal Investigator: Maciej Mrugala, MD            
Sponsors and Collaborators
Celldex Therapeutics
  More Information

No publications provided

Responsible Party: Celldex Therapeutics
ClinicalTrials.gov Identifier: NCT01498328     History of Changes
Other Study ID Numbers: CDX110-06
Study First Received: December 21, 2011
Last Updated: May 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Celldex Therapeutics:
EGFRvIII
Glioblastoma
Rindopepimut
CDX-110
Small cell
Giant cell
Brain Cancer
Brain Tumor
Gliosarcoma
 oligodendroglial
radiotherapy
chemoradiation
Tumor
Bevacizumab
Relapsed
Returned
Recurrent
EGFR variant III

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
 Neoplasms, Nerve Tissue
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 19, 2013