Newly diagnosed, surgically resected, EGFRvIII-positive Glioblastoma MedDRA version: 14.1 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Rindopepimut
Product Code: CDX-110
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: Rindopepimut
CAS Number: 946156-74-7
Current Sponsor code: CD
Sponsors
CELLDEX THERAPEUTICS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Histologically confirmed, newly diagnosed, de novo glioblastoma including the following variants of glioblastoma: small cell glioblastoma, giant cell glioblastoma, gliosarcoma and glioblastoma with oligodendroglial component. ? Attempted surgical resection (stereotactic biopsy only is not acceptable). Tumor tissue specimens (paraffin-embedded) from surgical resection must be available for central pathology review, MGMT status determination and analysis of EGFRvIII status. ? Age = 18 years. ? No history of malignancy (other than glioblastoma) during the last three years except non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer or cured, early-stage prostate cancer in a patient with PSA level less than ULN. ? No evidence of current drug or alcohol abuse. ? No allergy or hypersensitivity to KLH, GM-CSF (sargramostim; LEUKINE), polysorbate 80 or yeast-derived products, or a history of anaphylactic reactions to shellfish proteins. ? Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. ? Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations. CENTRALLY histologically confirmed, newly diagnosed, de novo glioblastoma including the following variants of glioblastoma: small cell glioblastoma, giant cell glioblastoma, gliosarcoma and glioblastoma with oligodendroglial component. ? Completed conventional chemoradiation, consisting of radiotherapy at a minimally acceptable total dose of at least 90% of the planned dose (usually 60 Gy) and concomitant TMZ chemotherapy (75 mg/m2 body surface area per day). Patients who received an incomplete course or lower dose of temozolomide may be eligible, provided all other entry criteria are met. ? Documented EGFRvIII-positive tumor status, determined by polymerase chain reaction (PCR) assay on tumor tissue, and MGMT methylation status performed at the designated central laboratory. ? Radiographic imaging from the post-operative period (ideally obtained within 72 hours of surgery, but acceptable if obtained up to the initiation of chemoradiation) and post-chemoradiation period (within 14 days of completion of chemoradiation) available for submission to the independent review committee. If multiple scans are performed within the period after surgery but prior to chemoradiation, all should be submitted. (Note: Although the preferred imaging modality is MRI, in certain circumstances where MRI is not possible for a particular patient, CT scans may be utilized. However, contrast-enhanced scans are required and the same imaging modality must be used from the post-chemoradiation scan throughout the study.). ? No unequivocal radiographic progression of disease during the pre-study chemoradiation period. This assessment should be based on review of the latest interpretable scan performed within the time interval between surgery and the first day of chemoradiation, as compared to the post-chemoradiation (baseline) scan. ? Candidate for, and agrees to receive, adjuvant (maintenance) TMZ 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 throughout the 7 days prior to randomization. ? Documented MMS
Exclusion criteria
Exclusion criteria: 1.History of malignancy (other than glioblastoma) during the last three years except non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer or cured, early-stage prostate cancer in a patient with PSA level less than ULN. 2. Evidence of current drug or alcohol abuse. 3. Allergy or hypersensitivity to KLH, GM-CSF (sargramostim; LEUKINE), polysorbate 80 or yeast-derived products, or a history of anaphylactic reactions to shellfish proteins. 4. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. Randomization 5. Unequivocal radiographic progression of disease during the pre-study chemoradiation period. This assessment should be based on review of the latest interpretable scan performed within the time interval between surgery and the first day of chemoradiation, as compared to the postchemoradiation(baseline) scan. 6. Diffuse leptomeningeal disease, gliomatosis cerebri or infra-tentorial disease. 7. History, presence, or suspicion of metastatic disease. 8. Additional treatment for glioblastoma, aside from surgical resection and chemoradiation with TMZ. Agents used for diagnosis, imaging or visualization, even if investigational, are not exclusionary. Exclusionary treatments would include, but are not limited to: stereotactic radiosurgery, placement of Gliadel® (carmustine; BCNU) wafers, any other intratumoral or intracavity treatment, receipt of other chemotherapies, bevacizumab, or investigational agents. 9. Active systemic infection requiring treatment. A patient with an infection controlled by therapy will not be excluded if the next inclusion criterion is met. 10. Severe acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with trial participation or trial drug administration or could interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into the trial. This includes but is not limited to the following: a) Known (no need for active screening) HIV or chronic hepatitis B or hepatitis C infection, b) Immuno-deficiency disease, c) Chronic renal disease / failure, d) Concurrent neurodegenerative disease, e) Cardiovascular: uncontrolled hypertension, unstable angina, myocardial infarction or symptomatic congestive heart failure within the past 12 months or serious uncontrolled cardiac arrhythmia, f) Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of the protocol. 11. Planned major surgery.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to explore, in a double-blind, controlled setting, whether the addition of rindopepimut/GM-CSF to adjuvant TMZ shows promising signals of improved OS in patients with newly diagnosed, resected, EGFRvIII-positive glioblastoma who have undergone resection and completed TMZ-based radiochemotherapy;Secondary Objective: ? Progression-free survival (PFS) and OS distributions. ? PFS probability at 6 (PFS6) and 12 (PFS12) months, OS probability at 12 months (OS 12) post-randomization will be examined. ? Safety profile characterized by type, frequency, severity and relationship to investigational therapy of adverse events and laboratory abnormalities. ? Objective tumor response rate (applicable only for patients with evaluable disease at study entry, as defined per RANO criteria (Ref. 43). An external, independent review of radiologic imaging, blinded to treatment allocation and investigator assessments, will be performed.;Primary end point(s): Overall survival (OS) rate at 24 months post-randomization;Timepoint(s) of evaluation of this end point: Date of subject death | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Progression-free survival (PFS) and OS distributions. ? PFS probability at 6 (PFS6) and 12 (PFS12) months, OS probability at 12 months (OS 12) post-randomization will be examined. ? Safety profile characterized by type, frequency, severity and relationship to investigational therapy of adverse events and laboratory abnormalities. ? Objective tumor response rate (applicable only for patients with evaluable disease at study entry, as defined per RANO criteria (Ref. 43). An external, independent review of radiologic imaging, blinded to treatment allocation and investigator assessments, will be performed.;Timepoint(s) of evaluation of this end point: Date of subject death | — |
Countries
Italy
Contacts
Public ContactRegulatory Affairs
Novella Clinical Ltd.
Outcome results
None listed