E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rectal cancer subjects undergoing neoadjuvant
chemoradiotherapy |
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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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038043 |
E.1.2 | Term | Rectal cancer Duke's C |
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 |
The objective of this mechanistic study is to determine the impact of L-BLP25 vaccine on the mucinous glycoprotein 1 - (MUC1) specific immune response in patients with newly diagnosed rectal cancer who are eligible for neoadjuvant therapy.
L-BLP25 is designed to induce an immune response that may lead to immune rejection of tumor tissues that aberrantly express MUC1 antigen. MUC1 is highly expressed in all colorectal cancers and since the adaptive immune system plays a role in the prognosis of rectal cancer, it is reasonable to speculate that the vaccination with L BLP25 might boost the tumor-specific immune response and increase the number of TILs.
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male and female subjects with histologically documented resectable rectal adenocarcinoma in stage II-IV.
2.Availability of tumor biopsy sufficient for immunological analysis.
3.Indication to receive neoadjuvant concomitant chemoradiotherapy consisting of a radiation dose of 45-52 Gy and capecitabine 825 mg/m² orally twice daily. The use of an equivalent schedule based on 5-fluorouracil (5-FU) is acceptable.
4.MRI small pelvis / CT thorax / abdomen (or X-ray thorax) to document absence of metastatic disease. Imaging must not be older than 6 weeks prior to randomization.
5.Eastern Cooperative Oncology Group (ECOG) performance 5. status of 0 or 1.
6.Written informed consent.
7.18 years of age.
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E.4 | Principal exclusion criteria |
1. Previous chemotherapy and/or previous radiotherapy of the pelvic region.
2. Relapsing disease.
3. Previous vaccination with any MUC1 vaccine and other therapeutic cancer vaccines.
4. Previous organ transplantation (bone marrow or solid organs).
5. Subjects with metastatic disease (except for solitary, resectable liver or lung metastases).
6. Inadequate hematological function (i.e. platelet count < 140*10^9/L, or WBC < 2.5*10^9/L, or hemoglobin < 90 g/L). Clinically significant hepatic dysfunction (i.e. alanine aminotransferase [ALT] > 2.5 times upper limit of normal [ULN], or aspartate aminotransferase [AST] > 2.5*ULN, or bilirubin > 1.5*ULN). Inadequate renal function (i.e. serum creatinine > 1.5*ULN).
7. Autoimmune diseases.
8. Recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; subjects who have hereditary or congenital immunodeficiencies.
9. Clinically significant cardiac disease, e.g. New York Heart Association classes III-IV; uncontrolled angina, uncontrolled arrhythmia or uncontrolled hypertension, myocardial infarction in the previous 6 months as confirmed by medical history and an electrocardiogram (ECG)
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E.5 End points |
E.5.1 | Primary end point(s) |
Intratumoral immune parameters and peripheral antigenspecific immune parameters (response to MUC1 and CEA) are the primary endpoints. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Analysis of primary endpoint will take place after all patients completed the study and database was locked.
For the safety monitoring committee there will be interim safety analyses during the study. |
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E.5.2 | Secondary end point(s) |
•Immunological changes from baseline in the tumor microenvironment [ Time Frame: 4 months ] [ Designated as safety issue: No ]
•Immunological changes compared to baseline in peripheral blood [ Time Frame: 4 months ] [ Designated as safety issue: No ]
•Immunological Response to Treatment in Relation to Microsatellite Instability (MSI) Status [ Time Frame: 4 months ] [ Designated as safety issue: No ]
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Analysis of secondary endpoints will take place after all patients completed the study and database was locked.
For the safety monitoring committee there will be interim safety analyses during the study. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | 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 | Information not present in EudraCT |
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 | Yes |
E.8.2.3.1 | Comparator description |
standard radiochemotherapy and surgery only (Arm C) |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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If the trial is not terminated for a reason given in Section 5.6 of the protocol, the trial is finished when the last evaluable subject has the Follow-up / End-of-Trial visit, about 4 months after randomization. |
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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 | |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |