E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pancreatic Cancer, post resection R0/R1 status, with tumor sequence confirmation of Ras mutations |
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E.1.1.1 | Medical condition in easily understood language |
Surgically removed tumor of the pancreas with alteration to the Ras gene. |
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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 | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033575 |
E.1.2 | Term | Pancreas cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of weekly followed by monthly doses of GI-4000 in combination with adjuvant gemcitabine versus adjuvant gemcitabine with placebo in post-resection pancreatic cancer patients, as measured by time to recurrence. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate secondary endpoints of disease response as measured by the duration of recurrence-free survival, time to mortality, duration of overall survival, changes in symptom scores, and CA 19-9 levels. 2.To evaluate the immunogenicity of GI-4000, as measured by antigen specific T-cell responses. Genome wide association studies including full length genomic sequencing in a subset of subjects will also be applied to the current study to evaluate whether genetic determinants can influence immune response to blinded study therapy (GI-4000 versus placebo) as well as clinical outcomes such as time to disease recurrence and mortality. 3. To evaluate the safety of GI-4000 in a regimen combined with gemcitabine, as measured by SAEs, discontinuation due to AEs, and dosing interruptions/reductions due to AEs.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1 Subjects must have resectable pancreas cancer, ductal adenocarcinoma type, with post-resection confirmation of non-metastatic disease. 2 Confirmed product related mutation in Ras from tumor sample. 3 ECOG performance status (PS) of ≤2 prior to randomization. 4 Confirmed R0 or R1 status post-resection. 5 Negative scratch test (immediate hypersensitivity, IgE mediated) to S. cerevisiae. 6 Age ≥18 years. 7 Signed, written, informed consent from the patient or legal representative before any study-specific procedures are performed
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E.4 | Principal exclusion criteria |
1 Non-resectable pancreatic cancer, or histologic types other than ductal adenocarcinoma (e.g. papillary cystoadenocarcinoma, mucinous cystoadenocarcinoma). Tumors classified as T4. 2 Prior chemotherapy, radiation therapy, targeted therapy, or immunotherapy for pancreatic cancer. 3 History of another cancer within the last 5 years with the exception of localized basal or squamous cell carcinoma of the skin, Stage 1A cervical cancer, or melanoma in situ. 4 History of splenectomy. 5 History of Crohn’s disease or ulcerative colitis. 6 History of major organ transplantation. 7 Concurrent and chronic therapy with corticosteroids (greater than 10 mg per day of prednisone or an equipotent dose of another corticosteroid) or any other immunosuppressive drugs. Use of dexamethasone as an antiemetic during gemcitabine dosing will be permitted during the trial. 8 History of allergy to S. cerevisiae. 9 Presence of an unstable or poorly controlled medical condition that in the opinion of the principal investigator may impair the ability of the subject to participate safely or to potentially benefit from the study. 10 Pregnancy and nursing mothers. 11 Alcohol and/or IV drug abuse within the past year. 12 Participation in any experimental treatment protocol or therapy within 28 days before screening (experimental peri-operative procedures such as the use of novel drains which are anticipated to affect the acute post-operative course, may be allowed after discussion with the medical monitor). 13 History of autoimmune disease (subjects with a history of resolved autoimmune thyroiditis may be eligible with consultation of the study medical monitor). 14 Known history of hypersensitivity to gemcitabine. 15. High risk for noncompliance with the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
Recurrence free survival at 15 months after randomization. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Duration of recurence free survival is number of days from randomization to the earlier date of disease progression or death due to any cause. |
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E.5.2 | Secondary end point(s) |
1. Time to mortality 2. Biochemical recurrence (CA19-9) 3. Duration of recurrence-free survival measured from the date of randomization 4. Duration of recurrence-free survival measured from the date of surgery 5. Duration of overall survival measured from the date of randomization 6. Duration of overall survival measured from the date of surgery 7. Longitudinal changes in CA 19-9 levels relative to the baseline level 8. Longitudinal changes in EORTC QLQ C30 symptom scores from baseline for nausea/vomiting, pain, and fatigue 9. Longitudinal changes in ECOG performance status scores from baseline
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Time to mortality - from randomization to subject's death 2. Biochemical recurrence (CA19-9), Longitudinal changes in CA 19-9 levels relative to the baseline level, Longitudinal changes in EORTC QLQ C30 symptom scores, Longitudinal changes in ECOG performance status scores - from screening to disease progression 3. Duration of recurrence-free survival measured from the date of randomization, Duration of overall survival measured from the date of randomization - from randomization to disease progression or death 4. Duration of recurrence-free survival measured from the date of surgery, Duration of overall survival measured from the date of surgery - from the surgery to disease progression or death
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
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 |
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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 | 5 |
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 | 5 |
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 |