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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Celldex Therapeutics
Sponsor:
Information provided by (Responsible Party):
Celldex Therapeutics
ClinicalTrials.gov Identifier:
NCT01498328
First received: December 21, 2011
Last updated: September 3, 2014
Last verified: September 2014
  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:


Further study details as provided by Celldex Therapeutics:

Primary Outcome Measures:
  • Groups 1 and 2: 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).

  • Group 2C: Objective Response Rate [ Time Frame: Every 8 weeks from Day 1 through progression or initiation of other anti-cancer therapy ] [ Designated as safety issue: No ]
    Evaluate the anti-tumor activity of rindopepimut in adult patients with relapsed glioblastoma, as measured by the objective response rate (ORR) for patients with measurable disease at study entry.


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 (PFS), and overall survival (OS) for Groups 1 and 2; and PFS6, overall PFS, and OS for Group 2C.

  • 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: 168
Study Start Date: December 2011
Estimated Primary Completion Date: June 2015 (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 and 2C: 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 three 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 and Group 2C patients are those who are refractory to bevacizumab (experienced recurrence or progression of glioblastoma while on bevacizumab or within 2 months of discontinuing 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. Documented EGFRvlll positive tumor status (central lab confirmation).
  4. First or second relapse of de novo glioblastoma or first diagnosis or first relapse of secondary glioblastoma.
  5. Previous treatment must include surgery, conventional radiation therapy and temozolomide (TMZ).
  6. Screening MRI must be obtained at least 4 weeks after any salvage surgery, and at least 12 weeks after radiation therapy.
  7. KPS of ≥ 70%.
  8. 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.
  9. Evaluable disease in Groups 1 and 2; measurable disease in Group 2C
  10. Life expectancy > 12 weeks.
  11. Patients in Group 2 and 2C must have had disease progression while receiving bevacizumab or within 2 months of treatment with bevacizumab.

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.
  9. Patients in Group 1 must not have received prior treatment with bevacizumab.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: Naveed Wagle, MD         
Kaiser Permanente Los Angeles Medical Center Recruiting
Los Angeles, California, United States, 90027
Contact: Sandra Baker-Bolden, RN    323-783-5532    sandra.t.baker@kp.org   
Principal Investigator: Richard Green, MD         
UC Irvine Chao Family Comprehensive Cancer Center Recruiting
Orange, California, United States, 92868
Contact: Daniela Bota, M.D., Ph.D    714-456-7214      
Principal Investigator: Daniela Bota, M.D., Ph.D         
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Thelma Munoz    415-353-2523    Munozt@neurosurg.ucsf.edu   
Principal Investigator: Nicholas Butowski, MD         
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 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, Connecticut
Hartford Hospital Not yet recruiting
Hartford, Connecticut, United States, 06102
Contact: Tamara Montgomery    860-972-9828    tamara.montgomery@hhchealth.org   
Contact: Kathryne Alexander    860-545-3553    kathy.alexander@hhchealth.org   
Principal Investigator: Alexandra Flowers, MD         
United States, Florida
University of Florida Withdrawn
Gainesville, Florida, United States, 32610
Memorial Cancer Institute Recruiting
Hollywood, Florida, United States, 33021
Contact: Norma Cuervo    954-265-6363    NCuervo@mhs.net   
Principal Investigator: Atif Hussein, MD         
Orlando Health, Inc. Recruiting
Orlando, Florida, United States, 32806
Contact: Mollie Geismer, RN, CCRP    321-841-1620    Cancerclinicaltrials@orlandohealth.com   
Principal Investigator: Nicholas Avgeropoulos, MD         
Tampa General Hospital Recruiting
Tampa, Florida, United States, 33606
Contact: Denise Fife, RN    813-844-7829    dafife@tgh.org   
Contact: Sharon Porth    813-844-7829    sharonaporth@tgh.org   
Principal Investigator: Lawrence Berk, MD         
United States, Georgia
Atlanta Cancer Care Recruiting
Atlanta, Georgia, United States, 30342
Contact: Kathy Frank    770-777-1315    kfrank@atlantacancercare.com   
Contact: Julie F Carney, RN, BSN    770-777-1315    jcarney@atlantacancercare.com   
Principal Investigator: Ronald G Steis, MD         
Piedmont Atlanta Hospital Recruiting
Atlanta, Georgia, United States, 30309
Contact: Erin Dunbar, MD    404-605-2050      
Contact: Michelle Humphreys    404-425-7943      
Principal Investigator: Erin Dunbar, 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   
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   
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, Maryland
The Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Michael Lim, MD    410-614-1627      
Contact: Susan Zhen, RN    410-502-4081      
Principal Investigator: Michael Lim, MD         
United States, Massachusetts
Dana-Farber Cancer Institute and Mass General Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Jorge Dietrich, MD    617-643-1935    jdietrich1@partners.org   
Contact: Karley Griffen, RN, OCN    617-632-6749    karley.griffen@dfci.harvard.edu   
Principal Investigator: David A Reardon, MD         
United States, Michigan
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Larry Junck, MD    734-936-7910    ljunck@umich.edu   
Contact    1-800-865-1125    canceranswerline@umich.edu   
Principal Investigator: Larry Junck, MD         
Sparrow Cancer Center Recruiting
Lansing, Michigan, United States, 48912
Contact: Vicki Gilreath, RN, OCN    517-364-2811    Vicki.Gilreath@sparrow.org   
Principal Investigator: Gordan Srkalovic, MD, PhD         
United States, Minnesota
John Nasseff Neuroscience Institute, Abbott Northwestern Hospital, 800 e. 28th Str. MR Recruiting
Minneapolis, Minnesota, United States, 55407
Contact: Amy Schrecengost, BS, CCRC    612-863-3452      
Contact: Nilanjana Banerji, PhD    612-863-3452      
Principal Investigator: John E Trusheim, MD         
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Madelyn Kissel    314-747-5384    mkissel@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 Jersey
New Jersey Neuroscience Institute JFK Medical Center Recruiting
Edison, New Jersey, United States, 08818
Contact: Charles Porbeni, MD, MSC    732-321-7000 ext 68897      
Contact: Nnamdi A Uhegwu, MD    732-321-7000 ext 62623      
Principal Investigator: Joseph Landolfi, DO         
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Lori Cappello, RN    551-996-5098    lcappello@hackensackumc.org   
Principal Investigator: Samuel Goldlust, MD         
United States, New York
Dent Neurologic Institute, 3980 Sheridan Dr, 3rd Flr Clinical Rsch Recruiting
Amherst, New York, United States, 14226
Contact: Olga Ananina, B.S., CCRC    716-558-5670    oananina@dentinstitute.com   
Principal Investigator: Laszlo Mechtler, M.D.         
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         
Stony Brook University Hospital Recruiting
Stony Brook, New York, United States, 11794-8121
Contact: Susan Fiore, MS    631-444-9425    susan.fiore@stonybrookmedicine.edu   
Contact: Daryl McHugh, BA       daryl.mchugh@stonybrookmedicine.edu   
Principal Investigator: Agnes Kowalska, 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: Suzie Sifri    513-584-0618      
Principal Investigator: Richard Curry, 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   
Contact: Gina Cascone    216-983-3021    gina.cascone@uhhospitals.org   
Principal Investigator: Andrew Sloan, MD         
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 Active, not recruiting
Portland, Oregon, United States, 97232
United States, Pennsylvania
Lehigh Valley Hospital-John and Dorothy Morgan Cancer Center Recruiting
Allentown, Pennsylvania, United States, 18103
Contact: Yasmin Candelo, RN    610-402-9543      
Contact: Kathleen Bolsover, RN    610-402-9543      
Principal Investigator: Tara Morrison, MD         
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Eileen Maloney-Wilensky, MSN,RN, MHA and MSN, CRNP    267-809-2525      
Contact: Suzanne Frangos, RN, CNRN    215-285-2885    frangoss@uphs.upenn.edu   
Principal Investigator: James Schuster, MD         
University of Pittsburgh Cancer Institute Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Melinda Vargas-Jaffe, RN    412-235-1320    vargasjaffeme@upmc.edu   
Contact: Kelli Davis, RN, MSN    (412) 235-1316    skoviraka@upmc.edu   
Principal Investigator: Jan Drappatz, MD         
United States, Rhode Island
Rhode Island Hospital Active, not recruiting
Providence, Rhode Island, United States, 02903
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Reid C Thompson, MD    800-811-8480      
Principal Investigator: Reid C Thompson, MD         
United States, Texas
Texas Oncology Midtown Recruiting
Austin, Texas, United States, 78705
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: Sara Gonzales    214-820-6168    sara.gonzales@baylorhealth.edu   
Principal Investigator: Karen Fink, MD PhD         
UT Health Science Center, Houston Memorial Hermann Hospital, 6400 Fannin Street, #2800 Recruiting
Houston, Texas, United States, 77030
Contact: Greg Lu    713-704-2359    guangrong@uth.tmc.edu   
Contact: Jay-Jiguang Zhu, MD, PhD.    713-704-7100      
Sub-Investigator: Jay-Jiguang Zhu, MD, PhD.         
Principal Investigator: Sigmund Hsu, MD         
United States, Utah
Utah Cancer Specialists Recruiting
Salt Lake City, Utah, United States, 84116
Contact: Nitin Chandramouli, MD    801-269-0231      
Contact: Robbyn Oliver    801-267-5605    roliver@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         
Swedish Neuroscience Research Recruiting
Seattle, Washington, United States, 98122
Contact: Nathan Hansen    206-320-3542    nathan.hansen@swedish.org   
Contact: Mary Lessig    206-386-3878    mary.lessig@swedish.org   
Principal Investigator: Tara Benkers, 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: September 3, 2014
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
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014