A Randomized, Placebo-controlled, Double-blind Phase II Study Evaluating if Glucophage Can Avoid Liver Injury Due to Chemotherapy Associated Steatosis
NCT ID: NCT01523639
Last Updated: 2018-12-19
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE2
8 participants
INTERVENTIONAL
2012-04-30
2014-04-30
Brief Summary
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Approximately 10 sites in Austria will participate in the study. Subjects will be randomized in a ratio of 1:1 into two groups.
Detailed Description
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Wild-type KRAS is required for study entry. Further target-related parameters, based on current scientific knowledge may be assessed.
Subjects are randomized to Arm A or Arm B Arm A: FOLFIRI in combination with cetuximab and metformin Arm B: FOLFIRI in combination with cetuximab and placebo
A liver biopsy of hepatic metastasis and normal liver tissue is planned before the first cycle and at the end of treatment; with regard to the primary study objective, these subjects are evaluable.
Both efficacy and safety data will be collected. The investigators will assess response to treatment every 8 weeks based on imaging.
Following permanent treatment cessation, subjects will be followed-up for survival.
One interim analysis for futility (54 evaluable patients) and in addition two safety analysis for evaluation of reported adverse events between the two treatment groups will be performed at two different timepoints (20 evaluable patients/54 evaluable patients).
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Metformin
FOLFIRI + cetuximab + metformin every 2 weeks for 12 cycles
Metformin/Placebo
The starting dose of Metformin/Placebo is 500 mg p.o. twice daily for 7 days (daily dose 1000 mg p.o.). Dose will be increased to 1000 mg p.o. twice daily at day 8 (daily dose 2000 mg p.o.) unless no toxicity ≥ 2 due to IMP occurs.
Duration of treatment: 24 weeks
Placebo
FOLFIRI + cetuximab + placebo every 2 weeks for 12 cycles
Metformin/Placebo
The starting dose of Metformin/Placebo is 500 mg p.o. twice daily for 7 days (daily dose 1000 mg p.o.). Dose will be increased to 1000 mg p.o. twice daily at day 8 (daily dose 2000 mg p.o.) unless no toxicity ≥ 2 due to IMP occurs.
Duration of treatment: 24 weeks
Interventions
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Metformin/Placebo
The starting dose of Metformin/Placebo is 500 mg p.o. twice daily for 7 days (daily dose 1000 mg p.o.). Dose will be increased to 1000 mg p.o. twice daily at day 8 (daily dose 2000 mg p.o.) unless no toxicity ≥ 2 due to IMP occurs.
Duration of treatment: 24 weeks
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Male or female \>= 18 years of age
* Diagnosis of histologically confirmed, KRAS "wild-type" adenocarcinoma of the colon or rectum
* Non-resectable metastatic colorectal carcinoma
* Either presence of at least one liver lesion measurable unidimensionally by CT scan or MRI or at least one resectable liver metastasis with non-resectable extrahepatic disease (as assessed within 3 weeks prior to randomisation)
* Subjects scheduled to receive cetuximab and FOLFIRI
* ECOG performance status of 0 - 1 at study entry
* Leukocytes \>= 3.0 x 10\^9/L and neutrophils \>= 1.5 x 10\^9/L, platelets \>= 100 x 10\^9/L, and hemoglobin \>= 8 g/dL
* Bilirubin \<= 1.5 x ULN
* ASAT and ALAT \<= 5 x ULN
Exclusion Criteria
* Previous chemotherapy for the currently existing metastatic disease
* Known or newly diagnosed diabetes
* Patients with ACS within the last three months
* Stage 3 or 4 heart failure defined according to the NYHA criteria
* Uncontrolled angina
* Contraindications to metformin (renal impairment \[eGFR \<45 mL/min/1.73m\^2\], known hypersensitivity to metformin, acute illness \[dehydration, severe infection, shock, acute cardiac failure\]), and suspected tissue hypoxia
* Surgery (excl. diagnostic biopsy, central venous catheter) or irradiation within 2 weeks prior to study entry defined as given written informed consent
* Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol
* Administration of any investigational agent(s) within 4 weeks prior to study entry,
* Previous exposure to EGFR-pathway targeting therapy
* Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease
* Known grade 3 or 4 allergic reaction to any of the components of the treatment
* Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix. (Subjects with a previous malignancy but without evidence of disease for \>= 5 years will be allowed to enter the trial)
* Pregnancy or lactation
* Inadequate contraception (male or female patients) if of childbearing or procreative potential
* Known drug abuse/ alcohol abuse
* Legal incapacity or limited contractual capacity Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent
18 Years
ALL
No
Sponsors
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Merck Gesellschaft mbH, Austria
INDUSTRY
Austrian Breast & Colorectal Cancer Study Group
NETWORK
Responsible Party
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Principal Investigators
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Birgit Gruenberger, MD
Role: PRINCIPAL_INVESTIGATOR
Austrian Breast & Colorectal Cancer Study Group
Locations
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Medical University Graz, Oncology
Graz, Styria, Austria
Medical University Innsbruck, Internal Medicine
Innsbruck, Tyrol, Austria
Hospital St. Vinzenz
Zams, Tyrol, Austria
Hospital BHS Ried
Ried, Upper Austria, Austria
KH BHB Vienna
Vienna, , Austria
Med. Univ. Vienna, General Hospital Vienna
Vienna, , Austria
KH St. Josef KH
Vienna, , Austria
Countries
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References
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Other Identifiers
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200084-610
Identifier Type: OTHER
Identifier Source: secondary_id
2011-001010-34
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
G-LUCAS
Identifier Type: -
Identifier Source: org_study_id