Efficacy Study of a Maintenance Therapy With Immunomodulator MGN1703 in Patients With Advanced Colorectal Carcinoma

Advanced Colorectal Carcinoma Clinical Trial

— IMPACT  

Official title:

Phase 2, Randomized, Double-blind, Placebo-controlled, Multi-Center Study of a Maintenance Therapy With Immunomodulator MGN1703 in Patients With Advanced Colorectal Carcinoma With Disease Control After Initial First-line Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01208194
• Other study ID #: MGN1703-C02
• Secondary ID: 2009-017432-40
• Status: Completed
• Phase: Phase 2
• First received: August 27, 2010
• Last updated: June 19, 2014
• Start date: June 2010
• Est. completion date: March 2013

Study information

• Verified date: June 2014
• Source: Mologen AG
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-InstitutAustria: Federal Office for Safety in Health CareUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyFrance: Agence Francaise de Securite Sanitaire des Produits de SanteRussian Federation: Ministry of Healthcare and Social Development of the Russian FederationCzech Republic: State Institute for Drug Control
• Study type: Interventional

Clinical Trial Summary

This is a phase 2, randomized, double-blind, multi-center clinical study to evaluate efficacy and safety of a maintenance therapy with the immunomodulator MGN1703 compared to placebo control. The study will be conducted in patients with advanced colorectal carcinoma (AJCC Stage IV) with disease control after first-line standard chemotherapy regimens.

Description:

The phase 2 study will be conducted in patients with advanced colorectal carcinoma with disease control after first-line standard chemotherapy regimens with oral or intravenous fluoropyrimidines/leucovorin and irinotecan or oxaliplatin combined with a standard dose of bevacizumab lasted between 4.5 and 6 months, whereas the treatment duration with irinotecan or oxaliplatin should not be less than 3 months. Studies confirmed that completely chemotherapy-free intervals can be applicable in patients with advanced colorectal carcinoma who achieved disease control after initial first-line chemotherapy. Those therapy holidays minimize toxicity and unnecessary treatment load, reduce intensity of treatment, allow patients to stay longer on therapy, prevent therapy discontinuations due to toxicity, preserve the ability to re-administer chemotherapy later, and increase quality of life of the patients. The therapy-free interval represents a possibility to evaluate the efficacy of the study drug, MGN1703.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: March 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male and female subjects older than 18 years of age

• Histologically confirmed colorectal carcinoma

• Radiological confirmation of unresectable advanced colorectal carcinoma (AJCC Stage IV) prior to start of initial first-line therapy

• At least one measurable lesion according to RECIST measured within 2 weeks prior to treatment start in case of partial response or stable disease

• Prior initial first-line therapy included oral or intravenous fluoropyrimidines/leucovorin,irinotecan or oxaliplatin with or without a standard dose of bevacizumab lasted between 4.5 and 6 months and finished (last day of last cycle) within 2 weeks prior to treatment start (treatment duration with irinotecan or oxaliplatin should not be less than 3 months)

• Patients who achieved disease control measured as objective response or disease stabilization after initial first-line therapy

• No curative standard therapy is available for the patient after first-line treatment

• ECOG performance status 0-1

• Adequate organ function, hemoglobin = 9 g/L, white blood cell count (WBC) = 3.0 x 109/L, absolute neutrophil count = 1.5 x 109/L, platelets > 100 x109/L, aspartate and alanine aminotransferase (AST and ALT) = 2.5 x ULN, bilirubin < 1.5 x ULN, blood creatinine = 1.5 X ULN, prothrombin time (PT) and activated thromboplastin time (aPTT) within normal range

• Negative pregnancy test in women with childbearing potential

• Expected adequacy of follow-up

• Signed informed consent form (ICF)

Exclusion Criteria:

• More than one line of systemic chemotherapy for metastatic colorectal carcinoma

• Tumor progression after initial first-line therapy

• Clinically significant concomitant diseases or conditions, which in opinion of the investigator would lead to an unacceptable risk for the subject to participate in the study

• Prior or current other malignancy, except adequately treated superficial bladder cancer, basal or squamous cell carcinoma of the skin or other cancer for which the subject has been disease free for more than 3 years

• Known central nervous system metastases

• Active or uncontrolled infections

• Transfusion-dependent anemia

• History of autoimmune disease or immune deficiency

• Known hypersensitivity to oligonucleotides or excipients of the formulation

• Pregnancy and/or nursing

• Concurrent chronic systemic immune therapy or immunosuppressant medication, including steroid treatment

• Concurrent chemotherapy, hormonal therapy (except hormonal contraception and hormonal replacement therapy for menopausal women), or immunotherapy within the last 2 weeks prior to randomization or during the conduct of the study - Concurrent radiotherapy within the last 6 months prior to randomization or during the conduct of the study

• Known HIV seropositivity or active hepatitis B or C infection

• Planned major surgery during the study

• Participation in another clinical study with other investigational drugs within 30 days prior to the first treatment day

• Vaccination within 3 months prior to the first treatment day

• Any medical, mental, psychological or psychiatric condition which in opinion of the investigator would not permit the subject to complete the study or understand the patient information

• Presence of drug and/or alcohol abuse

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Colorectal Carcinoma
• Carcinoma
• Colorectal Neoplasms

Intervention

Drug:
• MGN1703
solution, 60 mg, twice a week, until progression
• Placebo
solution, 60 mg, twice a week, until progression

Locations

Country	Name	City	State
Austria	Klinik für Innere Medizin I, Abteilung für Klinische Onkologie, Medizinische Universität Wien	Wien
Czech Republic	Oncology Clinic, Faculty Hospital Olomouc	Olomouc
France	Service de Cancérologie Digestive, Institut de Cancérologie Gustave Roussy	Villejuif
Germany	Onkologischer Schwerpunkt am Oskar-Helene-Heim	Berlin
Germany	Klinik für Innere Medizin IV, Onkologie/ Hämatologie/ Hämostaseologie, Universitätsklinikum Halle (Saale)	Halle
Germany	Kath. Marienkrankenhaus GmbH, Allgemeine Onkologie	Hamburg
Germany	Schwerpunktpraxis für Hämatologie und Onkologie	Magdeburg
Germany	Klinik für Innere Medizin, Klinik für Hämatologie, Onkologie, Immunologie, Universitätsklinikum Giessen und Marburg GmbH	Marburg
Germany	Medizinische Klinik, Abteilung für Onkologie, Hämatologie Immunologie, Rheumatologie und Pulmologie Universität Tübingen, Immuntherapie, Station 65 Med. Klinik Abt. II	Tübingen
Russian Federation	Non-state health care institution "Central Clinical Hospital No. 2 named after N.A. Semashko OAO "RZHD"	Moscow
Russian Federation	State Institution "Russian Scientific Oncology Center named after N.N. Blokhin RAMN"	Moscow
United Kingdom	Mount Vernon Cancer Centre	Northwood	Middlesex

Sponsors (1)

Lead Sponsor	Collaborator
Mologen AG

Countries where clinical trial is conducted

Austria,  Czech Republic,  France,  Germany,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of median progression-free survival (PFS) in both treatment groups		Measured on accrual time 3 years	No
Secondary	Assessment of PFS rate		Measured at landmarks 12, 18 and 24 weeks after treatment start, and afterwards every 6 weeks until treatment stop	No
Secondary	Evaluation of median overall survival (OS)		Measured on accrual time 3 years	No
Secondary	Assessment of OS proportion in both groups		Measured at landmarks 12, 18 and 24 weeks after treatment start, and afterwards every 6 weeks until treatment stop	No
Secondary	Evaluation of overall response rate (ORR)		Measured on accrual time 3 years	No
Secondary	Evaluation of duration of response (complete response, partial response, stable disease) as time from initial determination of response to progressive disease measured by RECIST		Measured on accrual time 3 years	No
Secondary	Assessment of the dynamic of clinical and laboratory parameters		An average time: participants are followed until progress	No
Secondary	Evaluation of immunologic response to MGN1703		An average time: participants are followed until progress	No
Secondary	Assessment of quality of life (QOL)		An average time: participants are followed until progress	No
Secondary	Assessment of the safety profile of MGN1703		An average time: participants are followed until progress	No