Clinical trial NCT01462513: L-BLP25 in Patients With Colorectal Carcinoma After Curative Resection of Hepatic Metastases
Official title: LICC: L-BLP25 in Patients With Colorectal Carcinoma After Curative Resection of Hepatic Metastases - a Randomized, Placebo-controlled, Multicenter, Multinational, Double Blinded Phase II Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colon Carcinoma
Rectum Carcinoma
Keywords: Colon carcinoma
Rectum carcinoma
Liver metastases
Lead sponsor: Johannes Gutenberg University Mainz
Sponsor class: OTHER
First posted: 2011-10-31
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Comparative evaluation of recurrence-free survival (RFS) time and 3 year overall survival (OS) time between the treatment groups (L-BLP25 plus cyclophosphamide versus placebo and saline infusion).

Detailed description: This trial is designed for patients with metastatic colorectal carcinoma (CRC), who have undergone a complete resection of their primary tumor and recent resection of their liver metastases (R0 or R1) with curative intent. No generally accepted standard care is available following curative-intent resection of hepatic metastases in colorectal cancer patients. L-BLP25 is a cancer vaccine that targets MUC1, a well known tumor-associated antigen. Recently, it has been shown that MUC1 is associated with cellular transformation as demonstrated by tumorigenicity and can confer resistance to genotoxic agents. High levels of MUC1 cell surface expression, reported immunosuppressive activities of its released ectodomain, and anti-adhesive properties all contribute to the ability of the MUC1 antigen to protect and promote tumor cell growth and survival, and make MUC1 an attractive target for cancer immunotherapy.

Based on these results, L BLP25 may have potential as adjuvant therapy after curative resection of hepatic metastases in colorectal cancer patients.

Eligibility criteria: Inclusion Criteria:

* Signed written informed consent.
* Female patients of childbearing potential (and if appropriate male patients with female partners of childbearing potential) must be willing to use an adequate method of contraception for 4 weeks prior to, during and 12 weeks after the last dose of trial medication. A negative pregnancy test is required for female subjects. Adequate contraception for female subjects is defined as two barrier methods, or one barrier method with a spermicide, or intrauterine device or use of hormonal female contraceptive.
* Histologically confirmed diagnosis of adenocarcinoma of the colon or rectum with complete resection of primary tumor and no evidence of local relapse.
* Metastatic disease of the liver, with recent (\< 8 weeks prior to randomization), both primary or secondary resection (R0 or R1) of all liver metastases. Metastasectomy may have been either synchronous or metachronous. Neoadjuvant therapy may have been applied prior to metastasectomy.
* Subject has had a colonoscopy or rectoscopy within the last three months prior to initiation of therapy
* Subject has an ECOG performance status of 0 or 1.
* Subject has adequate hematologic, hepatic, and renal function within 2 weeks prior to initiation of therapy as defined by the following: Absolute neutrophils \> 1,500/mm3 and platelets \> 140,000/mm3. Bilirubin \< 1.5 x upper limit of normal (ULN). AST and ALT \< 2.5 x ULN. Creatinine \< 1.5 x ULN.
* International Normalized Ratio (INR) and partial thromboplastin time (PTT) within normal range respectively within therapeutic range in case of anticoagulation.
* Willingness to comply with study protocol requirements.

Exclusion Criteria:

* Metastases other than liver metastases.
* R2 and Rx resected liver metastases. Patients with R1 resected liver metastases can be included if a further surgical resection is seen as not indicated or necessary in the surgeon´s opinion.
* Chemotherapy within 4 weeks prior to randomization.
* Receipt of immunotherapy (e.g. interferons, tumor necrosis factor, interleukins, or growth factors \[GM-CSF, G-CSF, M- CSF\], monoclonal antibodies) within 4 weeks (28 days) prior to randomization.
* Any known autoimmune disease, past or current.
* A recognized immunodeficiency disease including cellular immuno-deficiencies, hypogammaglobulinemia or dysgammaglobulinemia; hereditary or congenital immunodeficiencies.
* Known or newly diagnosed active hepatitis B infection and/or hepatitis C infection, autoimmune hepatitis, known human immunodeficiency virus infection, or any other infectious process that in the opinion of the investigator could compromise the subject's ability to mount an immune response, or expose him/ her to likelihood of more and/or severe side effects.
* Past or current history of malignant neoplasm other than CRC, except for curatively treated non-melanoma skin cancer, in-situ carcinoma of the cervix or other cancer curatively treated and with no evidence of disease for at least 5 years.
* Medical or psychiatric conditions that would interfere with ability to provide informed consent, communicate side effects, or comply with protocol requirements.
* Clinically significant cardiac disease, e.g. cardiac failure of New York Heart Association classes III-IV; uncontrolled angina pectoris, uncontrolled arrhythmia, uncontrolled hypertension, myocardial infarction in the previous 12 months as confirmed by an ECG.
* Splenectomy.
* Previous (less than 4 weeks prior to randomization) or concurrent treatment with a non-permitted drug.
* Pregnancy and lactation period.
* Participation in another clinical study within 30 days prior to randomization.
* Known hypersensitivity to the study treatment drugs.
* Known alcohol or drug abuse.
* Legal incapacity or limited legal capacity.
* Any other reason that, in the opinion of the investigator, precludes the subject from participating in this study.

Primary outcomes:
measure: Comparative evaluation of recurrence-free survival (RFS) time and 3 year overall survival (OS) time between the treatment groups (L-BLP25 plus cyclophosphamide versus placebo and saline infusion).
timeFrame: until December 2017
Secondary outcomes:
measure: Safety / Tolerability
timeFrame: until December 2017
measure: Recurrence-free survival time in the subgroup of MUC1 positive cancers
timeFrame: until December 2017
measure: Overall survival time in a subgroup of MUC1 positive cancers
timeFrame: until December 2017
Other outcomes:
Locations:
city: Salzburg
country: Austria
facility: Salzburger Universitätsklinikum, Universitätsklinik für Innere Medizin III
city: Altenburg
country: Germany
facility: Klinikum Altenburger Land
city: Berlin
country: Germany
facility: Campus Virchow-Klinikum, Charite Centrum 8
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt
city: Essen
country: Germany
facility: Universitätsklinikum Essen WTZ-Ambulanz, Innere Medizin (Tumorforschung)
city: Esslingen
country: Germany
facility: Klinik für Allgemeine Innere Medizin, Onkologie / Hämatologie
city: Frankfurt
country: Germany
facility: Klinikum der Johann W- Goethe Unversität, Klinik für Allgemein- und Viszeralchirurgie
city: Hamburg
country: Germany
facility: Onkologische Schwerpunktpraxis Eppendorf
city: Karlsruhe
country: Germany
facility: Städtisches Klinikium Abt. Allgemein- und Visceralchirurgie
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
city: Marburg
country: Germany
facility: Universtitäsmedizin Gießen und Marburg
city: Mülheim an der Ruhr
country: Germany
facility: Praxis für Hämatologie und Onkologie
city: München
country: Germany
facility: Klinikum der Universität München-Grosshadern, Medizinische Klinik III
city: Offenburg
country: Germany
facility: GP für Hämatologie und Onkologie Offenburg
city: Recklinghausen
country: Germany
facility: Oncologianova GmbH
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Stuttgart
country: Germany
facility: Robert-Bosch Krankenhaus, Zentrum für Innere Medizin
city: Trier
country: Germany
facility: Krankenhaus der Barmherzigen Brüder
city: Weiden
country: Germany
facility: Klinikum Weiden, Medizinische Klinik I
Study officials:
affiliation: Universitätsmedizin Mainz
name: Carl Christoph Schimanski, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schimanski CC, Kasper S, Hegewisch-Becker S, Schroder J, Overkamp F, Kullmann F, Bechstein WO, Vohringer M, Ollinger R, Lordick F, Heinemann V, Geissler M, Schulz-Abelius A, Bernhard H, Schon MR, Greil R, Galle P, Lang H, Schmidtmann I, Moehler M. Adjuvant MUC vaccination with tecemotide after resection of colorectal liver metastases: a randomized, double-blind, placebo-controlled, multicenter AIO phase II trial (LICC). Oncoimmunology. 2020 Aug 23;9(1):1806680. doi: 10.1080/2162402X.2020.1806680.