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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 July 2014 by Celldex Therapeutics
Sponsor:
Information provided by (Responsible Party):
Celldex Therapeutics
ClinicalTrials.gov Identifier:
NCT01498328
First received: December 21, 2011
Last updated: July 8, 2014
Last verified: July 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

  Show 48 Study Locations
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: July 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Celldex Therapeutics:
Rindopepimut
EGFRvIII
Glioblastoma
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 August 28, 2014