Rectal cancer subjects undergoing neoadjuvant chemoradiotherapy MedDRA version: 14.1 Level: LLT Classification code 10038043 Term: Rectal cancer Duke's C System Organ Class: 100000004864
Conditions
Sponsors
Merck KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
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. 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 44 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 44
Exclusion criteria
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 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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. ;Secondary Objective: ;Primary end point(s): Intratumoral immune parameters and peripheral antigenspecific immune parameters (response to MUC1 and CEA) are the primary endpoints.;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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 ] ;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. | — |
Countries
Austria, Belgium, Germany, Netherlands, Portugal
Contacts
Public ContactCommunication Centre Merck KGaA
Merck KGaA
Outcome results
None listed