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

Phase 2

Completed

• Conditions: Recurrent Glioblastoma; Small Cell Glioblastoma; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Glioblastoma With Oligodendroglial Component; Relapsed Glioblastoma
• Interventions: Drug: Bevacizumab; Drug: Rindopepimut (CDX-110) with GM-CSF; Drug: KLH

• Registration Number: NCT01498328
• Lead Sponsor: Celldex Therapeutics

Brief 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.

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.

Study Timeline

• Study Start: 2011-12
• Study First Submitted: 2011-12-21
• Study First Submitted QC: 2011-12-22
• Study First Posted: 2011-12-23
• Primary Completion: 2015-04
• Study Completion: 2016-05-17
• Status Verified: 2017-04
• Disposition First Submitted: 2017-04-06
• Disposition First Submitted QC: 2017-04-06
• Disposition First Posted: 2017-04-07
• Last Update Submitted: 2020-02-12
• Last Update Posted: 2020-02-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 127

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1a: Bevacizumab Naïve with Bevacizumab + rindopepimut.	Bevacizumab	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.
Group 1a: Bevacizumab Naïve with Bevacizumab + rindopepimut.	Rindopepimut (CDX-110) with GM-CSF	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.
Group 1b: Bevacizumab Naïve with Bevacizumab + KLH control	KLH	About half of the patients who have never received treatment with bevacizumab will receive KLH in a blinded fashion in combination with bevacizumab.
Group 2 and 2C: Refractory to Bevacizumab	Rindopepimut (CDX-110) with GM-CSF	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).
Group 1b: Bevacizumab Naïve with Bevacizumab + KLH control	Bevacizumab	About half of the patients who have never received treatment with bevacizumab will receive KLH in a blinded fashion in combination with bevacizumab.
Group 2 and 2C: Refractory to Bevacizumab	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).

Primary Outcome Measures

Name	Time	Method
Groups 1 and 2: Progression-free survival rate	6 months post-Day 1	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	Every 8 weeks from Day 1 through progression or initiation of other anti-cancer therapy	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

Name	Time	Method
EGFRvIII-specific immune response	Several times during the first month of treatment and then approximately every 8 weeks until treatment is stopped.	Characterize the EGFRvIII specific immune response to rindopepimut.
Safety and Tolerability	Until 28 days or initiation of other anti-cancer treatment, whichever is first	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	During treatment and every 8 weeks through follow up	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.

Trial Locations

Locations (45)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

St. Joseph's Hospital and Medical Center / Barrow Neurological Institute; 🇺🇸 Phoenix, Arizona, 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

UC Irvine Chao Family Comprehensive Cancer Center; 🇺🇸 Orange, California, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Stanford Cancer Institute, Stanford University; 🇺🇸 Stanford, California, United States

University of Colorado, Denver; 🇺🇸 Aurora, Colorado, United States

Memorial Cancer Institute; 🇺🇸 Hollywood, Florida, United States

Orlando Health, Inc.; 🇺🇸 Orlando, Florida, United States

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