E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Maintenance treatment with Cvac in patients with resected stage I or stage II adenocarcinoma (cancer) of the pancreas |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of pancreatic cancer |
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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 | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033609 |
E.1.2 | Term | Pancreatic carcinoma |
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 |
To assess the safety and tolerability of Cvac in patients with resected stage I or stage II adenocarcinoma (cancer) of the pancreas |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives • To assess the duration of Progression-Free Survival (PFS) and Overall Survival (OS) following the initiation of Cvac in this patient population
Exploratory Objectives • To evaluate the time to next treatment (TTNT) • To evaluate immunologic response to Cvac administration in this patient population • To investigate biomarkers, including tumor and immune characteristics, of clinical efficacy of Cvac in this patient population • To assess the change in quality of life (QoL) following the initiation of Cvac in this patient population
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients may be enrolled if they meet all of the following criteria at screening: 1. Histologically or cytologically diagnosed adenocarcinoma of the pancreas, stage I or stage II disease; 2. Postoperative confirmed R0 or R1 resection status with no evidence of residual disease based on radiographic imaging; 3. CA 19-9 less than 2 × the ULN by the central laboratory; 4. No greater than 6 weeks since completion of prior therapy, which includes surgery with or without radiation or chemotherapy; 5. Mucin 1-positive tumor as determined by central immunohistopathology. Sites will be asked to submit archival tissue (patients may start the study if tissue is available at an outside hospital, but not yet requested or received); 6. Signed an ICF; 7. Willing and able to complete study procedures within the study timelines; 8. Life expectancy of at least 6 months in the investigator’s opinion; 9. ≥ 18 years of age; 10. ECOG performance status < 2 (Karnofsky ≥ 70%); 11. Normal organ and marrow function: serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN and serum bilirubin ≤ 1.5 × ULN unless Gilbert’s syndrome has previously been confirmed for the patient, white blood cells (WBCs) ≥ 3.0 K/µL, absolute neutrophil count (ANC) ≥ 1.0 × 109/L, hemoglobin ≥ 8 g/dL, and platelets ≥ 100 × 109/L; 12. Not pregnant, and if of childbearing potential, agrees to use a highly effective method of birth control (implanted, injectable, or oral combination hormonal method alone or in possible combinations, intrauterine device, vasectomized partner, or abstinence) prior to study entry, for the duration of the study, and for 3 months after the last dose of Cvac. Male partners of a study patient must use a condom in addition to the acceptable method of contraception for the female partner as specified above. |
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E.4 | Principal exclusion criteria |
1. Active, acute, or chronic clinically significant infections or bleeding; 2. Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg) or history of congestive heart failure (≥ Grade 2); 3. Active angina pectoris, stroke, or recent myocardial infarction (within 6 months); 4. Additional uncontrolled, serious medical or psychiatric illness; 5. Evidence or history of central nervous system metastases; 6. Inadequate renal function defined as a creatinine clearance < 60 mL/min as determined by the central laboratory; 7. Additional malignancy diagnosed within 5 years of study enrolment, except carcinoma in situ of the cervix or basal cell and squamous cell carcinomas of the skin; 8. Treatment with any other investigational agent (for any condition) within 4 weeks of screening; 9. Infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or syphilis (Treponema pallidum [TPHA]); 10. Concurrent systemic treatment with steroids or other immunosuppressant agents at a dose considered by the investigator to be higher than a standard physiological dose; 11. Active autoimmune disease; any previous autoimmune disease must not require chronic treatment in the 6 months prior to screening.
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
See Protocol Table 1 for Schedule of Safety and Tolerability Assessments
Safety and tolerability will be assessed by the following: • Adverse events evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4 • Clinically relevant changes from baseline in vital signs • Clinically relevant changes from screening in 12-lead ECG • Clinically relevant changes from baseline in physical examinations • Clinically relevant changes from baseline in safety laboratory assessments (haematology with differential count, biochemistry, and urinalysis) • Clinically relevant autoantibody laboratory assessments
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E.5.2 | Secondary end point(s) |
EFFICACY ENDPOINTS The efficacy endpoints for this pilot study include OS and PFS. OS is defined as the number of days between the start date of treatment with Cvac and the date of death from any cause. The duration of OS will be right-censored based on the date the patient was last known to be alive for those who are alive or lost to follow-up as of the data analysis cut off date.
PFS is defined as the number of days between the start date of treatment with Cvac and the earlier of documented disease progression as defined by RECIST criteria or death without prior progression. The date of disease progression or censoring for PFS will be determined according to the conventions listed in the May 2007 FDA Guidance for Industry, ‘Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics’ (www.fda.gov/cder/guidance/7478fnl.htm).
QUALITY OF LIFE Change from baseline for the following QoL measures: • European Organization for Research and Treatment of Cancer–Quality of Life Questionnaire (EORTC QLQ-C30, version 3) • Module QLQ-PAN26
EXPLORATORY ENDPOINTS • Time to Next Treatment (TTNT) • Change in immunologic parameters • Change in CA 19-9 • Change in ECOG performance status • Change in tumour and immune biomarkers (protein and RNA)
DEFINITIONS • TTNT is defined as the time from baseline (Week 0) to the date when a next treatment for Pancreatic cancer is started. • PFS is defined as the time from baseline (Week 0) to the date of the radiological scan used to determine PD or date of death from any cause (PFS event). • Each patient will be assessed for PD per standard of care at the clinical site, until PD is determined by the investigator, or until death, or until end of study, whichever occurs first for the patient. • Radiological scans should be performed using the same technique (CT or MRI) throughout the study if possible. • QoL will be assessed at baseline, after each dose of study agent, and at PFS Follow-Up Visits.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
See Protocol Table 1 for Schedule of Efficacy and Other Assessments
OVERALL SURVIVAL After documented PD, approximately every 24 weeks for at least 3 years following baseline or until death or the end of the study, investigators will continue to contact patients or caretakers to assess survival.
PROGRESSION-FREE SURVIVAL Each patient will be assessed for PD at approximately 12 weeks after baseline, and then every 12 weeks thereafter, until PD is determined by the investigator, or until death, or until the end of the study, whichever occurs first. For any patients who progress and continue to receive Cvac, the date and type of response (e.g., stable disease, disease progression) should be collected for any subsequent radiological scans completed. |
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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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
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 | No |
E.8.2.3 | Other | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Bulgaria |
Germany |
Poland |
Ukraine |
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E.8.7 | Trial has a data monitoring committee | No |
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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DURATION OF THE STUDY: Patient enrollment is expected to occur over approximately 12 months. The maximum time on study is estimated at approximately 47 months (screening period, 44 weeks of treatment, and 36 months of post-treatment evaluation). Follow-up visits will be made every 12 weeks until PD and then telephone contacts every 24 weeks until, death or end of study, whichever occurs first . |
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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 |