LICC: L-BLP25 in Patients With Colorectal Carcinoma After Curative Resection of Hepatic Metastases

Sponsor

Prof. Dr. Carl Schimanski (Other)

Overall Status

Completed

CT.gov ID

NCT01462513

Collaborator

(none)

122

Enrollment

Locations

Arms

Duration (Months)

5.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Colon Carcinoma Rectum Carcinoma	Biological: L-BLP25 Biological: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

122 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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 Start Date :

Aug 1, 2011

Actual Primary Completion Date :

Dec 31, 2017

Actual Study Completion Date :

Jan 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: L-BLP25 L-BLP25 treatment	Biological: L-BLP25 Treatment: 930µg per treatment once weekly for 8 weeks, then at 6-week intervals during years 1 and 2. Other Names: MUC1-antibody
Placebo Comparator: Placebo Placebo	Biological: Placebo Treatment: Placebo 930µg per treatment, once weekly for 8 weeks, then at 6-week intervals during years 1 and 2.

Arm

Intervention/Treatment

Experimental: L-BLP25

L-BLP25 treatment

Biological: L-BLP25

Treatment: 930µg per treatment once weekly for 8 weeks, then at 6-week intervals during years 1 and 2.

Other Names:

MUC1-antibody

Placebo Comparator: Placebo

Placebo

Biological: Placebo

Treatment: Placebo 930µg per treatment, once weekly for 8 weeks, then at 6-week intervals during years 1 and 2.

Outcome Measures

Primary Outcome Measures

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). [until December 2017]
The primary variable of this trial is recurrence free survival (RFS) time. RFS time will be measured from the date of randomization to the date of recurrence. For subjects not known to have experienced recurrence or death at the time of analysis, the time between the date of randomization and the date of last evaluation for recurrence will be calculated and used as a censored observation in the analysis.

Secondary Outcome Measures

Safety / Tolerability [until December 2017]
Assessment of safety will include: AEs, SAEs Vital signs (body temperature, respiratory rate, heart rate, and blood pressure) and physical examinations, Clinical laboratory assessments from hematology and biochemistry samples
Recurrence-free survival time in the subgroup of MUC1 positive cancers [until December 2017]
Recurrence free survival (RFS) time of MUC1 positive cancers will be measured from the date of randomization to the date of relapse based on standard imaging. For subjects not known to have experienced recurrence or death at the time of analysis, the time between the date of randomization and the date of last evaluation for recurrence or death will be calculated and used as a censored observation in the analysis.
Overall survival time in a subgroup of MUC1 positive cancers [until December 2017]
Overall survival time of MUC1 positive cancers will be measured from the date of randomization to the date of death. For subjects not known to be deceased at the time of analysis, the time between the date of randomization and the date of last contact, or date lost to follow-up, will be calculated and used as a censored observation in the analysis.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Salzburger Universitätsklinikum, Universitätsklinik für Innere Medizin III	Salzburg	Austria	5020
2	Klinikum Altenburger Land	Altenburg	Germany	04600
3	Campus Virchow-Klinikum, Charite Centrum 8	Berlin	Germany	13353
4	Klinikum Darmstadt	Darmstadt	Germany	64283
5	Universitätsklinikum Essen WTZ-Ambulanz, Innere Medizin (Tumorforschung)	Essen	Germany	45122
6	Klinik für Allgemeine Innere Medizin, Onkologie / Hämatologie	Esslingen	Germany	73730
7	Klinikum der Johann W- Goethe Unversität, Klinik für Allgemein- und Viszeralchirurgie	Frankfurt	Germany	60590
8	Onkologische Schwerpunktpraxis Eppendorf	Hamburg	Germany	20249
9	Städtisches Klinikium Abt. Allgemein- und Visceralchirurgie	Karlsruhe	Germany	76133
10	Universitätsklinikum Leipzig	Leipzig	Germany	04103
11	Universitätsklinikum Magdeburg	Magdeburg	Germany	39120
12	Universitätsmedizin Mainz	Mainz	Germany	55131
13	Universtitäsmedizin Gießen und Marburg	Marburg	Germany	35033
14	Praxis für Hämatologie und Onkologie	Mülheim an der Ruhr	Germany	45468
15	Klinikum der Universität München-Grosshadern, Medizinische Klinik III	München	Germany	81377
16	GP für Hämatologie und Onkologie Offenburg	Offenburg	Germany	77654
17	Oncologianova GmbH	Recklinghausen	Germany	45657
18	Universitätsklinikum Regensburg	Regensburg	Germany	93042
19	Robert-Bosch Krankenhaus, Zentrum für Innere Medizin	Stuttgart	Germany	70376
20	Krankenhaus der Barmherzigen Brüder	Trier	Germany	54292
21	Klinikum Weiden, Medizinische Klinik I	Weiden	Germany	92637