Tecemotide (L-BLP25) in Rectal Cancer (SPRINT)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01507103
First received: January 6, 2012
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

The objective of this mechanistic study is to determine the impact of Tecemotide (L-BLP25) administration on the mucin 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 L BLP25 administration might boost the tumor-specific immune response and increase the number of tumor-infiltrating lymphocytes (TILs).


Condition Intervention Phase
Rectal Cancer
Other: Chemoradiation Therapy
Drug: Cyclophosphamide (CPA)
Other: Biological: Tecemotide (L-BLP25)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Change from Baseline in tumor-infiltrating lymphocytes (TILs) evaluated by immunohistochemical analysis at Month 4 [ Time Frame: Baseline and Month 4 ] [ Designated as safety issue: No ]
  • Change from Baseline in the Enzyme-linked Immunosorbent Spot (ELISPOT) level of MUC1-specific T-cells at Month 4 [ Time Frame: Baseline and Month 4 ] [ Designated as safety issue: No ]
  • Change from Baseline in the Enzyme-linked Immunosorbent Spot (ELISPOT) level of carcinoembryonic antigen (CEA)-specific T-cells at Month 4 [ Time Frame: Baseline and Month 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Immunological changes from Baseline in the tumor microenvironment at Month 4 [ Time Frame: Baseline and Month 4 ] [ Designated as safety issue: No ]
  • Immunological changes from Baseline in peripheral blood at Month 4 [ Time Frame: Baseline and Month 4 ] [ 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 ]

Enrollment: 124
Study Start Date: February 2012
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemoradiation Therapy, L-BLP25 with Cyclophosphamide (CPA)
Following randomization, subjects in this investigational arm will receive, a single intravenous infusion of CPA, 300 milligram per square meter (mg/m^2) (to a maximum of 600 milligram), three days before the first Tecemotide (L-BLP25) administration. Subjects will then receive Tecemotide (L-BLP25), 806 microgram, as eight consecutive weekly subcutaneous administration (primary treatment phase) followed by ninth Tecemotide (L-BLP25) administration 7-11 days prior to surgery.
Other: Chemoradiation Therapy
Radiotherapy: 45-52 grays (Gy) will be applied for 5 weeks. Oral Capecitabine (825 mg/m^2, twice daily) or 5-fluorouracil (5-FU), starting at the first day of radiotherapy and given 5-7 days per week during the time of radiotherapy.
Drug: Cyclophosphamide (CPA)
A single intravenous infusion of 300 milligram per square meter (to a maximum of 600 milligram) of CPA will be given 3 days before the first Tecemotide (L-BLP25) administration.
Other Names:
  • L01AA01
  • Endoxana
Other: Biological: Tecemotide (L-BLP25)
Eight consecutive weekly subcutaneous administrations with reconstituted Tecemotide (L-BLP25), 806 microgram (concomitant to chemoradiation), followed by ninth Tecemotide (L-BLP25) administrations 7-11 days prior to surgery.
Other Names:
  • EMD531444
  • Tecemotide
Experimental: Chemoradiation Therapy, Tecemotide (L-BLP25)
Following randomization, subjects in this investigational arm will receive Tecemotide (L-BLP25), 806 microgram, as eight consecutive weekly subcutaneous administration (primary treatment phase) followed by ninth Tecemotide (L-BLP25) administration 7-11 days prior to surgery.
Other: Chemoradiation Therapy
Radiotherapy: 45-52 grays (Gy) will be applied for 5 weeks. Oral Capecitabine (825 mg/m^2, twice daily) or 5-fluorouracil (5-FU), starting at the first day of radiotherapy and given 5-7 days per week during the time of radiotherapy.
Other: Biological: Tecemotide (L-BLP25)
Eight consecutive weekly subcutaneous administrations with reconstituted Tecemotide (L-BLP25), 806 microgram (concomitant to chemoradiation), followed by ninth Tecemotide (L-BLP25) administrations 7-11 days prior to surgery.
Other Names:
  • EMD531444
  • Tecemotide
Active Comparator: Chemoradiation Therapy
Following randomization, subjects in this comparator arm will receive, standard neoadjuvant treatment.
Other: Chemoradiation Therapy
Radiotherapy: 45-52 grays (Gy) will be applied for 5 weeks. Oral Capecitabine (825 mg/m^2, twice daily) or 5-fluorouracil (5-FU), starting at the first day of radiotherapy and given 5-7 days per week during the time of radiotherapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 (MRI) small pelvis / computed tomography (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 status of 0 or 1
  6. Written informed consent
  7. 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 [g/L]). Clinically significant hepatic dysfunction (that is alanine aminotransferase [ALT] greater than 2.5*upper limit of normal [ULN], or aspartate aminotransferase [AST] 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 (ECG)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01507103

Locations
Netherlands
NKI (Nederlands Kanker Instituut)
Amsterdam, Netherlands
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Prof. Sonia Quaratino Merck KGaA
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01507103     History of Changes
Other Study ID Numbers: EMR063325-013, 2011-000847-25
Study First Received: January 6, 2012
Last Updated: January 29, 2014
Health Authority: Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Portugal: National Pharmacy and Medicines Institute

Keywords provided by Merck KGaA:
Tecemotide (L-BLP25)
Cyclophosphamide
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

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents
Cyclophosphamide
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on April 17, 2014