A Phase II Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma
Overview
- Phase
- Phase 2
- Intervention
- Bevacizumab
- Conditions
- Glioblastoma
- Sponsor
- Celldex Therapeutics
- Enrollment
- 127
- Locations
- 45
- Primary Endpoint
- Groups 1 and 2: Progression-free survival rate
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility 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).
- •Documented EGFRvlll positive tumor status (central lab confirmation).
- •First or second relapse of de novo glioblastoma or first diagnosis or first relapse of secondary glioblastoma.
- •Previous treatment must include surgery, conventional radiation therapy and temozolomide (TMZ).
- •Screening MRI must be obtained at least 4 weeks after any salvage surgery, and at least 12 weeks after radiation therapy.
- •KPS of ≥ 70%.
- •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
- •Evaluable disease in Groups 1 and 2; measurable disease in Group 2C
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
- •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.
- •Patients in Group 1 must not have received prior treatment with bevacizumab.
Arms & Interventions
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.
Intervention: Bevacizumab
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.
Intervention: Rindopepimut (CDX-110) with GM-CSF
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.
Intervention: Bevacizumab
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.
Intervention: KLH
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).
Intervention: Bevacizumab
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).
Intervention: Rindopepimut (CDX-110) with GM-CSF
Outcomes
Primary Outcomes
Groups 1 and 2: Progression-free survival rate
Time Frame: 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
Time Frame: 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 Outcomes
- Safety and Tolerability(Until 28 days or initiation of other anti-cancer treatment, whichever is first)
- Anti-tumor activity(During treatment and every 8 weeks through follow up)
- EGFRvIII-specific immune response(Several times during the first month of treatment and then approximately every 8 weeks until treatment is stopped.)