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

Glioblastoma Clinical Trial

— ReACT  

Official title:

A Phase II Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01498328
• Other study ID #: CDX110-06
• Status: Completed
• Phase: Phase 2
• Start date: December 2011
• Est. completion date: May 17, 2016

Study information

• Verified date: April 2017
• Source: Celldex Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: May 17, 2016
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Giant Cell Glioblastoma
• Glioblastoma
• Glioblastoma With Oligodendroglial Component
• Gliosarcoma
• Recurrent Glioblastoma
• Relapsed Glioblastoma
• Small Cell Glioblastoma

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Lehigh Valley Hospital-John and Dorothy Morgan Cancer Center	Allentown	Pennsylvania
United States	Dent Neurologic Institute, 3980 Sheridan Dr, 3rd Flr Clinical Rsch	Amherst	New York
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Atlanta Cancer Care	Atlanta	Georgia
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	University of Colorado, Denver	Aurora	Colorado
United States	Texas Oncology Midtown	Austin	Texas
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute and Mass General Hospital	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	University of Cincinnati Cancer Institute	Cincinnati	Ohio
United States	Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	The Long Island Brain Tumor Center at Neurology Surgery, P.C.	Commack	New York
United States	Baylor Research Institute	Dallas	Texas
United States	The Preston Robert Tisch Brain Tumor Center; Duke University Medical Center	Durham	North Carolina
United States	New Jersey Neuroscience Institute JFK Medical Center	Edison	New Jersey
United States	NorthShore University Health System	Evanston	Illinois
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Memorial Cancer Institute	Hollywood	Florida
United States	UT Health Science Center, Houston Memorial Hermann Hospital, 6400 Fannin Street, #2800	Houston	Texas
United States	Sparrow Cancer Center	Lansing	Michigan
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	University of Southern California (USC) Norris Comprehensive Cancer Center	Los Angeles	California
United States	John Nasseff Neuroscience Institute, Abbott Northwestern Hospital, 800 e. 28th Str. MR	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	UC Irvine Chao Family Comprehensive Cancer Center	Orange	California
United States	Orlando Health, Inc.	Orlando	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	St. Joseph's Hospital and Medical Center / Barrow Neurological Institute	Phoenix	Arizona
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Legacy Research Institute	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	University of Rochester Medical Center	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	University of California San Francisco	San Francisco	California
United States	Swedish Neuroscience Research	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Stanford Cancer Institute, Stanford University	Stanford	California
United States	Stony Brook University Hospital	Stony Brook	New York
United States	Tampa General Hospital	Tampa	Florida
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Celldex Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (1)

Reardon DA, Desjardins A, Vredenburgh JJ, O'Rourke DM, Tran DD, Fink KL, Nabors LB, Li G, Bota DA, Lukas RV, Ashby LS, Duic JP, Mrugala MM, Cruickshank S, Vitale L, He Y, Green JA, Yellin MJ, Turner CD, Keler T, Davis TA, Sampson JH; ReACT trial investiga — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Groups 1 and 2: Progression-free survival rate	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).	6 months post-Day 1
Primary	Group 2C: Objective Response Rate	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.	Every 8 weeks from Day 1 through progression or initiation of other anti-cancer therapy
Secondary	Safety and Tolerability	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	Until 28 days or initiation of other anti-cancer treatment, whichever is first
Secondary	Anti-tumor activity	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.	During treatment and every 8 weeks through follow up
Secondary	EGFRvIII-specific immune response	Characterize the EGFRvIII specific immune response to rindopepimut.	Several times during the first month of treatment and then approximately every 8 weeks until treatment is stopped.