An International, Randomized, Double-Blind, Controlled Study of Rindopepimut/GM-CSF with Adjuvant Temozolomide in Patients with Newly Diagnosed, Surgically Resected, EGFRvIII-positive Glioblastoma (The ACT IV” Study)

• Conditions: ewly Diagnosed, Surgically Resected, EGFRvIII-positive Glioblastoma; MedDRA version: 14.1Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-006068-32-GR
• Lead Sponsor: Celldex Therapeutics, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-10-19
• Last Update Posted: 2 May 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 440

Inclusion Criteria

Patients may be included in the study only if they meet all of the following inclusion criteria at the time of randomization:
1) Histologically confirmed, newly diagnosed, de novo glioblastoma including the following recognized variants of glioblastoma: small cell glioblastoma, giant cell glioblastoma, gliosarcoma and glioblastoma with oligodendroglial component (central pathologic review will be performed and histologic confirmation will be required prior to study entry).
2) Attempted surgical resection followed by conventional chemoradiation, consisting of radiotherapy at a minimally acceptable total dose of at least 90% of the planned dose (approximately 60 Gy) of absorbed radiation, concurrent with temozolomide at a targeted dose of 75 mg/m2
3) Tumor tissue specimens (paraffin-embedded) from surgical resection must be available for central pathology review, MGMT status determination and analysis of EGFRvIII status. body surface area per day. Patients who received an incomplete course of temozolomide may be eligible, provided inclusion criterion 7 is met.
4) Documented EGFRvIII positive tumor status, determined by polymerase chain reaction (PCR) assay on tumor tissue, performed at a sponsor-designated central laboratory.
5) Brain MRIs from the post-operative period (ideally obtained within 72 hours of surgery) and post-chemoradiation period (within 1-14 days of completion of chemoradiation) available for submission to the independent review committee by the time of randomization. (Note: In certain circumstances where MRI is not possible for a particular patient, CT scans may be utilized. However, the same imaging modality must be used from the post-chemoradiation scan throughout the study.)
6) No evidence of progressive disease from the post-operative period to the post-chemoradiation period, based on changes in the neurologic exam, steroid use, or evident radiographic progression, according to RANO criteria.
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 (Appendix 3) = 2 throughout the week prior to randomization.
10)Men or women 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 352
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 88

Exclusion Criteria

Patients will be excluded from the study for any of the following reasons:
1) Stereotactic biopsy only (without further surgical resection)
2) Presence of diffuse leptomeningeal disease or gliomatosis cerebri
3) History, presence, or suspicion of metastatic disease
4) Patients who have received any additional treatment for glioblastoma, aside from surgical resection and chemoradiation with temozolomide. 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 any other intratumoral or intracavity treatment, receipt of other chemotherapies, bevacizumab, or investigational agents.
5) Active systemic infection requiring treatment. A patient with an infection controlled by therapy will not be excluded 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.
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) HIV, or chronic hepatitis B or hepatitis C infection,
b) Immunosuppressive 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 keyhole limpet hemocyanin (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 clinical trial of medicinal product
• Study Design: Not specified