Phase III Study of Rindopepimut/GM-CSF in Patients With Newly Diagnosed Glioblastoma

Study Overview
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Brief Summary
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This 2-arm, randomized, phase III study will investigate the efficacy and safety of the addition of rindopepimut (an experimental cancer vaccine that may act to promote anti-cancer effects in patients who have tumors that express the EGFRvIII protein) to the current standard of care (temozolomide) in patients with recently diagnosed glioblastoma, a type of brain cancer. All patients will be administered temozolomide, the standard treatment for glioblastoma. Half the patients will be randomly assigned to receive rindopepimut and half the patients will be randomly assigned to receive a control called keyhole limpet hemocyanin. Patients will be treated in a blinded fashion (neither the patient or the doctor will know which arm of the study the patient is on). Patients will be treated until disease progression or intolerance to therapy and all patients will be followed for survival.

Detailed Description
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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 chemotherapy drug temozolomide can help improve the life expectancy of patients with newly diagnosed, resected EGFRvIII positive glioblastoma. The duration of participation in this study may be up to 5 years. After you are screened and enrolled in the study, you will be administered temozolomide and either rindopepimut/GM-CSF or KLH until either disease progression or intolerance to the medications. If your tumor progresses while on this study, your doctor may treat you with other therapies that are not part of the study.

Official Title
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An International, Randomized, Double-Blind, Controlled Study of Rindopepimut/GM-CSF With Adjuvant Temozolomide in Patients With Newly Diagnosed, Surgically Resected, EGFRvIII-positive Glioblastoma

Conditions
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Glioblastoma, Small Cell Glioblastoma, Giant Cell Glioblastoma, Gliosarcoma, Glioblastoma With Oligodendroglial Component

Intervention / Treatment
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* Drug: Rindopepimut (CDX-110) with GM-CSF
* Drug: Temozolomide
* Drug: KLH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria- Among other criteria, patients must meet the following conditions to be eligible for the study: Adult patients, ≥ 18 years old Newly diagnosed glioblastoma Attempted surgical resection followed by conventional chemoradiation Documented EGFRvIII positive tumor status by a Sponsor designated laboratory No evidence of progressive disease from the post-operative period to the post-chemoradiation period Candidate for, and agrees to receive, adjuvant (maintenance) temozolomide therapy Systemic corticosteroid therapy at ≤2 mg of dexamethasone or equivalent per day for at least 3 days prior to randomization WHO-ECOG Performance Status ≤ 2 Patients of childbearing/reproductive potential will be instructed to use birth control as defined by your doctor. Exclusion Criteria- Among other criteria, patients who meet the following conditions are NOT eligible for the study: Stereotactic biopsy only (without further surgical resection) Presence of diffuse leptomeningeal disease, gliomatosis cerebri, or infratentorial disease. History, presence, or suspicion of metastatic disease Patients who have received any additional treatment for glioblastoma, aside from surgical resection and chemoradiation with temozolomide Active systemic infection requiring treatment History of any malignancy (other than glioblastoma) during the last three years except non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer, cured, early-stage prostate cancer in a patient with PSA level less than ULN,or other carcinoma in situ that has been adequately treated and cured. Planned major surgery Evidence of current drug or alcohol abuse 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 Severe acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with participating in a clinical trial Women who are pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rindopepimut/GM-CSF plus Temozolomide<br> | Drug: Rindopepimut (CDX-110) with GM-CSF<br>* Two intradermal injections 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.<br>* Other names: CDX-110 with sargramostim (GM-CSF) (Leukine®);Drug: Temozolomide<br>* 150 to 200 mg/m2 for 5 days during each 28-day cycle for a minimum of six cycles or a maximum of 12 cycles, or until intolerance or progression.<br>* Other names: Temodal;|
| Active Comparator: KLH plus Temozolomide<br> | Drug: Temozolomide<br>* 150 to 200 mg/m2 for 5 days during each 28-day cycle for a minimum of six cycles or a maximum of 12 cycles, or until intolerance or progression.<br>* Other names: Temodal;Drug: KLH<br>* Two intradermal injections two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8mL containing approximately 100mcg of KLH.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The primary efficacy endpoint of Overall Survival is defined as the number of months from randomization to the date of death (whatever the cause), and will be censored for patients who remain alive at completion of the study for patients with a gross total resection ( n=374). The overall survival of patients will be monitored and compared between the two study arms until the end of the study. | During treatment and every three months from end of treatment through end of study or approximately up to 5 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Compare progression-free survival between the two treatment arms | Every 12 weeks from Day 1 through progression or initiation of other anti-cancer therapy | 
| Safety and Tolerability | Safety and tolerability will be measured by comparing the two arms in regards to vital sign measurement, physical and neurological examination, adverse events reporting, ECOG performance status, and EORTC core Quality of Life Questionnaire | Until day 28 of follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Giant cell, Gliosarcoma, EGFRvIII, Glioblastoma, Small cell, oligodendroglial, Brain Cancer, Brain Tumor, radiotherapy, chemoradiation, Tumor, temozolomide, EGFR variant III