A Randomized, Placebo-controlled, Double-blind Phase II Study Evaluating if Glucophage Can Avoid Liver Injury Due to Chemotherapy Associated Steatosis (G-LUCAS)
This study is currently recruiting participants.
Verified November 2012 by Austrian Breast & Colorectal Cancer Study Group
Sponsor:
Austrian Breast & Colorectal Cancer Study Group
Collaborator:
Merck Gesellschaft mbH, Austria
Information provided by (Responsible Party):
Austrian Breast & Colorectal Cancer Study Group
ClinicalTrials.gov Identifier:
NCT01523639
First received: January 26, 2012
Last updated: November 28, 2012
Last verified: November 2012
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Purpose
This multicenter randomized, placebo-controlled phase II study will enroll 132 first-line palliative treated subjects with metastatic KRAS wild type CRC. Subjects with histologically confirmed, KRAS wild-type CRC without previous chemo-therapy for metastatic disease will be screened for this study.
Approximately 10 sites in Austria will participate in the study. Subjects will be randomized in a ratio of 1:1 into two groups.
| Condition | Intervention | Phase |
|---|---|---|
|
Colorectal Cancer Steatohepatitis |
Drug: Metformin/Placebo |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | A Randomized, Placebo-controlled, Double-blind Multicenter Phase II Study to Investigate the Protectivity and Efficacy of Metformin Against Steatosis in Combination With FOLFIRI and Cetuximab in Subjects With First-line Palliative Treated, KRAS-Wild-Type, Metastatic Colorectal Cancer |
Resource links provided by NLM:
Further study details as provided by Austrian Breast & Colorectal Cancer Study Group:
Primary Outcome Measures:
- Reduction in the chemotherapy-associated steatosis [ Time Frame: up to 24 weeks ] [ Designated as safety issue: Yes ]Reduction in the chemotherapy-associated steatosis, as assessed by the steatosis subcore of NAFLD activity score (NAS)
Secondary Outcome Measures:
- Progression Free Survival [ Time Frame: up to 30 months ] [ Designated as safety issue: No ]PFS will be evaluated after final study visits. Subjects who terminate the study before their scheduled final study visits will be censored.
- Overall Survival [ Time Frame: up to 30 months ] [ Designated as safety issue: No ]OS will be evaluated after final study visits. Subjects who terminate the study before their scheduled final study visits will be censored.
- Safety assessment of all randomized subjects with at least one administration of study treatment [ Time Frame: up to 24 weeks ] [ Designated as safety issue: Yes ]All subjects who received at least one dose of IMP. Additional safety analyses of reported AEs will be performed after the evaluation of 20 and 54 patients (between the 2 treatment groups) at the time of interim analysis.
- Occured Adverse Events of all randomized subjects with at least one administration of study treatment [ Time Frame: up to 30 months ] [ Designated as safety issue: Yes ]All subjects who received at least one dose of IMP. Additional safety analyses of reported AEs will be performed after the evaluation of 20 and 54 patients (between the 2 treatment groups) at the time of interim analysis.
- Objective response rate (CR/PR) [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]Objective response rate (CR/PR), as assessed by RECIST criteria, version 1.1
- Reduction in chemo-therapy associated steatohepatitis (CASH) [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]Reduction in chemo-therapy associated steatohepatitis (CASH) as assessed by NAS
| Estimated Enrollment: | 132 |
| Study Start Date: | April 2012 |
| Estimated Study Completion Date: | July 2016 |
| Estimated Primary Completion Date: | December 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Metformin
FOLFIRI + cetuximab + metformin every 2 weeks for 12 cycles
|
Drug: 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 Name: Glucophage
|
|
Placebo Comparator: Placebo
FOLFIRI + cetuximab + placebo every 2 weeks for 12 cycles
|
Drug: 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 Name: Glucophage
|
Detailed Description:
This multicenter randomized, placebo-controlled phase II study will enroll 132 first-line palliative treated subjects with metastatic KRAS wild type CRC.
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).
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Signed written informed consent
- 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:
- Brain metastasis (if suspected, brain scan indicated)
- 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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01523639
Contacts
| Contact: Birgit Gruenberger, MD | +43-1-4080436 | birgit.gruenberger@chello.at |
| Contact: Gesa Ziesel, MSc | +43-1-4089230 ext 16 | gesa.ziesel@abcsg.at |
Locations
| Austria | |
| Medical University Graz, Oncology | Not yet recruiting |
| Graz, Styria, Austria, 8036 | |
| Contact: Hellmut Samonigg, MD +43-316-385 ext 13112 hellmut.samonigg@klinikum-graz.at | |
| Principal Investigator: Hellmut Samonigg, MD | |
| Medical University Innsbruck, Internal Medicine | Not yet recruiting |
| Innsbruck, Tyrol, Austria, 6020 | |
| Contact: Wolfgang Eisterer, MD +43-512-504 ext 23333 wolfgang.eisterer@i-med.ac.at | |
| Principal Investigator: Wolfgang Eisterer, MD | |
| Hospital St. Vinzenz | Not yet recruiting |
| Zams, Tyrol, Austria, 6511 | |
| Contact: Ewald Woell, MD +43-5442-600 ext 7421 e.woell@krankenhaus-zams.at | |
| Principal Investigator: Ewald Woell, MD | |
| Hospital BHS Ried | Recruiting |
| Ried, Upper Austria, Austria, 4910 | |
| Contact: Friedrich Renner, MD +43-7752-602 ext 1515 friedrich.renner@bhs.at | |
| Principal Investigator: Friedrich Renner, MD | |
| Med. Univ. Vienna, General Hospital Vienna | Recruiting |
| Vienna, Austria, 1090 | |
| Contact: Thomas Gruenberger, MD +43-1-40400 ext 5621 thomas.gruenberger@meduniwien.ac.at | |
| Principal Investigator: Thomas Gruenberger, MD | |
| KH BHB Vienna | Recruiting |
| Vienna, Austria, 1021 | |
| Contact: Birgit Gruenberger, MD +43-1-21121 ext 5168 birgit.gruenberger@bbwien.at | |
| Principal Investigator: Birgit Gruenberger, MD | |
| KH St. Josef KH | Not yet recruiting |
| Vienna, Austria, 1130 | |
| Contact: Leopold Oehler, MD, Head +43-1-87844 leopold.oehler@sjk-wien.at | |
| Principal Investigator: Leopold Oehler, MD, Head | |
Sponsors and Collaborators
Austrian Breast & Colorectal Cancer Study Group
Merck Gesellschaft mbH, Austria
Investigators
| Principal Investigator: | Birgit Gruenberger, MD | Austrian Breast & Colorectal Cancer Study Group |
More Information
Additional Information:
Publications:
| Responsible Party: | Austrian Breast & Colorectal Cancer Study Group |
| ClinicalTrials.gov Identifier: | NCT01523639 History of Changes |
| Other Study ID Numbers: | G-LUCAS, 200084-610, 2011-001010-34 |
| Study First Received: | January 26, 2012 |
| Last Updated: | November 28, 2012 |
| Health Authority: | Austria: Federal Office for Safety in Health Care |
Keywords provided by Austrian Breast & Colorectal Cancer Study Group:
|
liver injury steatosis KRAS-Wild-Type metastatic colorectal cancer |
metformin placebo chemotherapy |
Additional relevant MeSH terms:
|
Colorectal Neoplasms Fatty Liver Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases |
Colonic Diseases Intestinal Diseases Rectal Diseases Liver Diseases Metformin Hypoglycemic Agents Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 21, 2013