Clinical trial NCT01507103: Tecemotide (L-BLP25) in Rectal Cancer
Official title: A Multi-center, Randomized, Open-label, Mechanism of Action Trial on the Biological Effects of the Therapeutic Cancer Vaccine Stimuvax® (L-BLP25) in Rectal Cancer Subjects Undergoing Neoadjuvant Chemoradiotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: Tecemotide (L-BLP25)
Cyclophosphamide (CPA)
Mode of action
Neoplasms
Neoplasms by Site
Carcinomas
Antineoplastic Agents
Neoadjuvant
Radiotherapy Pharmacologic Actions
Immunosuppressive Agents
Immunologic Function
Therapeutic Uses
Molecular Mechanisms of Pharmacological Action
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2012-01-10
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this mechanistic study is to determine the impact of tecemotide (L-BLP25) administration on the mucinous glycoprotein 1 - (MUC1) specific immune response in subjects with newly diagnosed rectal cancer who are eligible for neoadjuvant therapy.

Tecemotide (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 tecemotide (L-BLP25) administration might boost the tumor-specific immune response and increase the number of tumor-infiltrating lymphocytes (TILs).


Eligibility criteria: Inclusion Criteria:

1. Male and female subjects with histologically documented resectable rectal adenocarcinoma in Stage 2-4
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/m\^2 orally twice daily. The use of an equivalent schedule based on 5-FU is acceptable
4. Magnetic resonance imaging small pelvis / computed tomography 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 performance status of 0 or 1
6. Written informed consent
7. Greater than or equal to (\>=) 18 years of age

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 (that is, platelet count less than 140\*10\^9 per liter \[/L\], or white blood cell less than 2.5\*10\^9/L, or hemoglobin less than 90 gram per liter). Clinically significant hepatic dysfunction (that is alanine aminotransferase greater than 2.5\*upper limit of normal \[ULN\], or aspartate aminotransferase greater than 2.5\*ULN, or bilirubin greater than 1.5\*ULN). Inadequate renal function (that is serum creatinine greater than 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, for example, 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
10. Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Change From Baseline in Tumor Immune Response Evaluated by Immunohistochemical (IHC) Analysis of Tumor Infiltrating Lymphocytes (TILs) at Week 14 (Post-surgery)
timeFrame: Baseline and Week 14 (post-surgery)
measure: Immunological Response to Treatment in Relation to Microsatellite Instability (MSI) Status: Number of Subjects Per MSI Category
timeFrame: 18 weeks
measure: Change From Baseline in Interferon (IFN)-Gamma Secretion of Mononuclear Cells in Response to MUC1 by Enzyme-linked Immunosorbent Spot (ELISpot) at Post-baseline
timeFrame: Baseline, Week 5, Week 13 (pre-surgery), and Week 18 (end-of trial)
measure: Change From Baseline in IFN-gamma Secretion of Mononuclear Cells in Response to Carcinoembryonic Antigen (CEA) by ELISpot at Post-baseline
timeFrame: Baseline, Week 5, Week 13 (pre-surgery), and Week 18 (end-of trial)
Secondary outcomes:
measure: Change From Baseline in Peritumoral Immune Response at Week 14 (Post-surgery)
timeFrame: Baseline and Week 14 (post-surgery)
measure: Change From Baseline in Immunological Response in Peripheral Blood at Week 18 (Follow-up / end-of Trial)
timeFrame: Baseline and Week 18 (follow-up / end-of trial)
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: NKI (Nederlands Kanker Instituut)
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Barbara Guenther
role: STUDY_DIRECTOR
References: