Tecemotide (L-BLP25) in Rectal Cancer
Condition: Rectal Cancer
MeSH terms: Rectal Neoplasms
Intervention: Tecemotide (L-BLP25); cyclophosphamide (CPA); Chemoradiotherapy
Intervention description: Subjects will receive 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 1, 2, 3, 4, 5, 6, 7 and 8, which will be administered concomitantly with the chemoradiotherapy, followed by a 9th subcutaneous injection 7 to 11 days prior to surgery.; A single intravenous infusion of 300 milligram per square meter (mg/m^2) (to a maximum 600 mg) of CPA will be given 3 days before the first tecemotide (L-BLP25) administration.; Radiotherapy of 45-52 grays (Gy) will be applied 5 times per week, over a minimum period of 5 weeks. Capecitabine at a dose of 825 mg/m^2, twice daily or equivalent dose of 5-fluorouracil (5-FU) will be given orally, starting at the first day of radiotherapy and given 5 to 7 days per week during the time of radiotherapy.
Intervention MeSH terms: Cyclophosphamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 124.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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

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