A Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma - Full Text View

Sponsor:	Celldex Therapeutics
Information provided by (Responsible Party):	Celldex Therapeutics
ClinicalTrials.gov Identifier:	NCT01498328

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: Cancer

Drug Information available for: Sargramostim Bevacizumab

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: Yes ]
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: Yes ]
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 bevacizumab will be administered rindopepimut/GM-CSF while continuing 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:

Age ≥18 years of age.
Histologic diagnosis of glioblastoma (WHO Grade IV).
Previous treatment for glioblastoma must include surgery,conventional radiation therapy and temozolomide (TMZ).
First or second relapse of primary glioblastoma.
Screening MRI must be obtained at least 4 weeks after any salvage surgery, and at least 12 weeks after radiation therapy.
KPS of ≥ 70%.
Life expectancy > 12 weeks.
Documented EGFRvIII positive tumor status by a Sponsor designated laboratory.
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.

Exclusion Criteria:

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

Subjects unable to undergo an MRI with contrast.
History, presence, or suspicion of metastatic disease
Prior receipt of vaccination against EGFRvIII.
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.
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.
Clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment
Evidence of recent hemorrhage on screening MRI of the brain
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

Show 22 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:	May 16, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Celldex Therapeutics:

EGFRvIII
Glioblastoma
Rindopepimut
CDX-110
Small cell
Giant cell
Gliosarcoma
oligodendroglial

radiotherapy
chemoradiation
Tumor
Bevacizumab
Relapsed
Returned
Recurrent

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 23, 2012