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

Sponsor

Mologen AG (Industry)

Overall Status

Completed

CT.gov ID

NCT01208194

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

4.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Colorectal Carcinoma	Drug: MGN1703 Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

59 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Study Start Date :

Jun 1, 2010

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Mar 1, 2013

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: MGN1703

Study medication

Drug: MGN1703

solution, 60 mg, twice a week, until progression

Other Names:

immunomodulator

Placebo Comparator: Placebo

Drug: Placebo

solution, 60 mg, twice a week, until progression

Outcome Measures

Primary Outcome Measures

Evaluation of median progression-free survival (PFS) in both treatment groups [Measured on accrual time 3 years]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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

Contacts and Locations

Locations

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