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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Colorectal Carcinoma
• Intervention / Treatment: Drug: MGN1703; Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
    • Klinik für Innere Medizin I, Abteilung für Klinische Onkologie, Medizinische Universität Wien
• Czech Republic
  • Olomouc, Czech Republic, 77520
    • Oncology Clinic, Faculty Hospital Olomouc
• France
  • Villejuif, France, 94805
    • Service de Cancérologie Digestive, Institut de Cancérologie Gustave Roussy
• Germany
  • Berlin, Germany, 14195
    • Onkologischer Schwerpunkt am Oskar-Helene-Heim
  • Halle, Germany, 06120
    • Klinik für Innere Medizin IV, Onkologie/ Hämatologie/ Hämostaseologie, Universitätsklinikum Halle (Saale)
  • Hamburg, Germany, 22087
    • Kath. Marienkrankenhaus GmbH, Allgemeine Onkologie
  • Magdeburg, Germany, 39104
    • Schwerpunktpraxis für Hämatologie und Onkologie
  • Marburg, Germany, 35043
    • Klinik für Innere Medizin, Klinik für Hämatologie, Onkologie, Immunologie, Universitätsklinikum Giessen und Marburg GmbH
  • Tübingen, Germany, 72076
    • Medizinische Klinik, Abteilung für Onkologie, Hämatologie Immunologie, Rheumatologie und Pulmologie Universität Tübingen, Immuntherapie, Station 65 Med. Klinik Abt. II
• Russian Federation
  • Moscow, Russian Federation, 115478
    • State Institution "Russian Scientific Oncology Center named after N.N. Blokhin RAMN"
  • Moscow, Russian Federation, 129128
    • Non-state health care institution "Central Clinical Hospital No. 2 named after N.A. Semashko OAO "RZHD"
• United Kingdom
  • Middlesex
    • Northwood, Middlesex, United Kingdom, HA6 2RN
      • Mount Vernon Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; solution, 60 mg, twice a week, until progression
Experimental: MGN1703; Study medication	Drug: MGN1703; solution, 60 mg, twice a week, until progression; Other Names: immunomodulator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluation of median progression-free survival (PFS) in both treatment groups	Measured on accrual time 3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Assessment of PFS rate	Measured at landmarks 12, 18 and 24 weeks after treatment start, and afterwards every 6 weeks until treatment stop
Evaluation of median overall survival (OS)	Measured on accrual time 3 years
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
Evaluation of overall response rate (ORR)	Measured on accrual time 3 years
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
Assessment of the dynamic of clinical and laboratory parameters	An average time: participants are followed until progress
Evaluation of immunologic response to MGN1703	An average time: participants are followed until progress
Assessment of quality of life (QOL)	An average time: participants are followed until progress
Assessment of the safety profile of MGN1703	An average time: participants are followed until progress

Collaborators and Investigators

• Sponsor: Mologen AG
• Investigators: Principal Investigator: Hans-Joachim Schmoll, Klinik für Innere Medizin IV, Universitätsklinikum Halle (Saale)

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: August 27, 2010
• First Submitted That Met QC Criteria: September 22, 2010
• First Posted (Estimate): September 23, 2010

Study Record Updates

• Last Update Posted (Estimate): June 20, 2014
• Last Update Submitted That Met QC Criteria: June 19, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Immunomodulator; Maintenance therapy; Advanced colorectal carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Carcinoma; Colorectal Neoplasms; Physiological Effects of Drugs; Immunologic Factors
• Other Study ID Numbers: MGN1703-C02; 2009-017432-40 (EudraCT Number)