E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018337 |
E.1.2 | Term | Glioblastoma multiforme |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to compare overall survival (OS) between patients randomized to DCVax-L and control patients from comparable, contemporaneous trials who received standard of care therapy only, in patients with newly diagnosed glioblastoma. This endpoint will be assessed using 3 different analyses |
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E.2.2 | Secondary objectives of the trial |
The first secondary objective is to compare overall survival (OS) between patients randomized to placebo who received DCVax-L treatment following disease recurrence and control patients from comparable, contemporaneous clinical trials, in patients with recurrent GBM. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Determined at pre-screening • Patients ≥18 and ≤70 years of age at surgery • Patients must be able to understand and sign the informed consent. The consent for tumor donation may be signed by a legally authorized representative (LAR) if allowed by the institution. • Patients must have a life expectancy of ≥8 weeks determined at or around surgery, and prior to pre-leukapheresis • Primary therapy must consist of surgical resection with the intent for a gross or near gross total resection of the contrast-enhancing tumor mass as confirmed by central review, followed by external beam radiation therapy and concurrent temozolomide chemotherapy. • Patients with newly diagnosed, unilateral GBM (Grade IV) without metastases are eligible for this protocol. • All Patients must have sufficient tumor lysate protein that was generated from the surgically obtained tumor material.
Determined at pre-leukapheresis • Patients must have adequate bone marrow function ( • Adequate liver function
Determined at baseline (or baseline2 for pseudoprogression patients) • Patients must have a KPS rating of ≥70 at the Baseline Visit (Visit 5) • Patients may have received steroid therapy as part of their primary treatment. Steroid treatment must preferably be stopped; or if continued steroid use is clinically indicated, be tapered down to 2-4 mg dexamethasone qd at least 7 days prior to the first immunization. • Patients must be willing to forego cytotoxic anti-tumor therapies except temozolomide while being treated with study drug. • A minimum of 5 immunizations must be available for treatment as determined by the contracted manufacturer. |
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E.4 | Principal exclusion criteria |
Determined at pre-screening • History of prior malignancy except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or other cancers that were deemed fully resolved 5 or more years prior to Visit 1 (surgery) of the study. • History of immunodeficiency disease or unresolved autoimmune disease • Known HIV-1,2, HTLV-1,2 or Hepatitis B, C infection • Pregnancy • Inability to obtain informed consent because of psychiatric or complicating medical problems. • Any known genetic cancer-susceptibility syndromes.
Determined at or around surgery • Bilateral or metastatic disease detected at diagnosis, during surgery or at post-surgical magnetic resonance imaging (MRI). Tumors may cross into, but not beyond the corpus callosum. • Post operative MRI scan evidence of biopsy only without significant tumor resection. • Implantation of Gliadel® wafers (polifeprosan 20 with carmustine implant) at surgery. • Positive test(s) for infectious agents (HIV 1 and 2, Anti-HIV-1,2, Hepatitis B, HBsAg, Anti HBc, Hepatitis C, Anti-HCV-Ab, Syphilis) that would preclude eligibility for tumor procurement and processing per manufacturing guidelines.
Determined at pre-leukapheresis • Positive HIV-1, HIV-2, HTLV-1, 2, hepatitis B surface antigen, or hepatitis C antibody. • Patients with organ allografts. • Allergies to reagents used in this study. • Patients who are unable to stop or taper steroid treatment to less than 8mg of dexamethasone qd prior to leukapheresis • Inability or unwillingness to return for required visits and follow-up exams. • Any previous cytotoxic drug therapies for the current disease. *note, cytotoxic therapy received for previous malignancies (resolved greater than 5 years prior) is not excluded
Determined at or prior to baseline • Patients who have evidence of disease progression (including possible pseudoprogression) as determined by central review are not eligible for the study • Patients taking medications that might affect immune function and that have documented anti-tumor activity. • Acute infection: any active viral, bacterial, or fungal infection that requires specific therapy. Antibiotic therapy must be completed at least 7 days prior to the first immunization. • Active uncontrolled infection e.g. a sexually transmitted disease (STD), herpes, uncontrolled tuberculosis, malaria, etc. • Fever ≥101.5oF. If considered possibly transient, retesting is allowed. • Unstable or severe intercurrent medical conditions e.g., unstable angina, uncontrolled arrhythmias, Crohn's Disease, ulcerative colitis etc. • Females of child-bearing potential who are pregnant or lactating or who are not using adequate contraception. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is overall survival (OS) compared between patients randomized to DCVax-L and control patients from comparable, contemporaneous trials who received standard of care therapy only, in patients with newly diagnosed glioblastoma.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The first secondary endpoint is overall survival (OS) compared between patients randomized to placebo who received DCVax-L treatment following disease recurrence, and control patients from comparable, contemporaneous clinical trials, in patients with recurrent GBM.
The second secondary endpoint, confirmed progression-free survival (cPFS), is confirmed disease progression (cPD) compared between subjects randomized to DCVax®-L and those randomized to Placebo within Study 020221.
The third secondary endpoint, PFS, is progression-free survival compared between subjects randomized to DCVax®-L and those randomized to Placebo within Study 020221.
The fourth secondary objective, OS, is overall survival compared between subjects randomized to DCVax®-L and those randomized to Placebo within Study 020221.
The fifth secondary objective is tumor response compared between subjects randomized to DCVax®-L and those randomized to Placebo within Study 020221. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Germany |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |