Tecemotide (L-BLP25) in Rectal Cancer

NCT ID: NCT01507103

Last Updated: 2017-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2014-06-30

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).

Conditions

Rectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chemoradiotherapy+tecemotide (L-BLP25)+CPA

Group Type: EXPERIMENTAL

Tecemotide (L-BLP25)

Intervention Type: BIOLOGICAL

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.

cyclophosphamide (CPA)

Intervention Type: DRUG

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.

Chemoradiotherapy

Intervention Type: OTHER

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.

Chemoradiotherapy+tecemotide (L-BLP25)

Group Type: EXPERIMENTAL

Tecemotide (L-BLP25)

Intervention Type: BIOLOGICAL

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.

Chemoradiotherapy

Intervention Type: OTHER

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.

Chemoradiotherapy

Group Type: ACTIVE_COMPARATOR

Chemoradiotherapy

Intervention Type: OTHER

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.

Interventions

Tecemotide (L-BLP25)

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.

Intervention Type: BIOLOGICAL

cyclophosphamide (CPA)

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.

Intervention Type: DRUG

Chemoradiotherapy

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 Type: OTHER

Other Intervention Names

EMD531444; L01AA01; Endoxana

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Barbara Guenther

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

NKI (Nederlands Kanker Instituut)

Amsterdam, , Netherlands

Countries

Netherlands

Other Identifiers

2011-000847-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EMR 63325-013

Identifier Type: -

Identifier Source: org_study_id