An International, Randomized, Double-Blind, Controlled Study of Rindopepimut/GM-CSF with Adjuvant Temozolomide in Patients with newly Diagnosed, Surgically Resected, EGFRvlll-positive Glioblastoma
- Conditions
- brain tumorGlioblastoma10029211
- Registration Number
- NL-OMON39791
- Lead Sponsor
- Celldex Therapeutics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 12
1.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.
2. Attempted surgical resection followed by convential chemoradiation, consisting of radiotherapy at a minimally acceptable total dose of at least 90% of the planned radiation therapy dose (usually 60Gy 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.
3. Tumor tissue specimens (paraffin-embedded) from surgical resection must be available for central pathology review, MGMT status determination and analysis of EGFRvIII status.
4. Documented EGFRvIII positive tumor status, determined by reverse transcriptase polymerase chain reaction (PCR) assay on tumor tissue, performed at a sponsor designated central laboratory.
5. 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-chemoradiationperiod (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).
6. 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.
7. Candidate for, and agrees to receive, adjuvant (maintenance) temozolomide therapy.
8. Systemic corticosteroid therapy at * 2 mg of dexamethasone or
equivalent per day for at least 3 days prior to randomization.
9. WHO-ECOG Performance Status * 2 throughout the 7 days prior to randomization.
10. Men or woman who are 18 years of age or older.
11. Patients of childbearing/reproductive potential should use highly effective method of birth control as defined by the investigator, for example those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner.
12. Personally signed and dated informed consent document indicating that the patient has been informed of and agreed with all pertinent aspects of the study.
D5a. In English
1. Stereotactic biopsy only (without further surgical resection).
2. Presence of diffuse leptomeningeal disease, gliomatosis cerebri or infra-tentorial disease
3.History, presence, or suspicion of metastatic disease
4. Patients who have received an 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.
5.Active systemic infection requiring treatment. Infection controlled by therapy will not be exclusionary provided it is not consistent with exclusion criterion 7.
6.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 or 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..
7.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.
8.Planned major surgery.
9.Evidence of current drug or alcohol abuse.
10.Women who are pregnant or lactating. All female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 7 days prior to starting treatment (Priming Day 1).
11.Known allergy or hypersensitivity to KLH, GM-CSF (sargramostim; LEUKINE®), polysorbate 80 or yeast-derived products, or a history of anaphylactic reactions to shellfish proteins.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary objective of the study is to confirm that the addition of<br /><br>rindopepimut/GM-CSF to adjuvant temozolomide improves overall survival in<br /><br>patients with newly diagnosed, resected, EGFRvIII positive glioblastoma who<br /><br>have undergone gross-total resection.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Compare Progression-Free Survival between the two treatment arms<br /><br>* Further characterize the safety and tolerability profile of the rindopepimut<br /><br>vaccination in combination with temozolomide<br /><br>* Assess health-related quality of life and symptom severity/interference using<br /><br>the patient-reported tools, QLQ-C30/BN20 and MDASI-BT.<br /><br>* Compare objective tumor response rates between the two treatment arms<br /><br>(applicable only for patients with evaluable disease at study entry, as defined<br /><br>per RANO criteria).<br /><br>Correlative Objectives:<br /><br>* Further characterize the EGFRvIII-specific immune response to rindopepimut<br /><br>vaccinations and the overall immunogenicity of the vaccine<br /><br>* Assess whether treatment with rindopepimut/GM-CSF results in elimination of<br /><br>EGFRvIII expression</p><br>