Metastatic Colorectal CancerPhase 2CEBIFOXNCT01051167
Bi-weekly Cetuximab Combined With 5-fluorouracil/Leucovorin/Oxaliplatin (FOLFOX-6) in Metastatic Colorectal Cancer
A Phase 2 study testing Cetuximab in people with Metastatic Colorectal Cancer, run by Martin Schuler, Prof. Dr. med. at 3 sites in Germany.
Trial summary
Cetuximab is normally given as a weekly schedule in the therapy of patients with metastatic colorectal cancer. In order to improve the convenience for the patients in first line-therapy this study will evaluate the efficacy and safety of a bi-weekly combination of cetuximab with FOLFOX. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 3 sitesGermany
- Study dates
- Feb 2009to Sep 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven metastatic colorectal cancer
- Molecular test showing no mutation in the k-ras gene of colorectal carcinoma cells
- Male and female subjects ≥ 18 years of age
- 1st occurrence of metastatic disease (not curatively resectable)
- Life expectancy ≥ 12 weeks
- Presence of at least 1 bi-dimensionally measurable index lesion (not in an irradiated area)
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- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at study entry
- Adequate bone marrow reserve:
- leucocytes ≥ 3.0 x 109/l with neutrophils ≥ 1.5 x 109/l, platelets ≥ 100 x 109/l, haemoglobin ≥ 6.21 mmol/l (10 g/dl)
- Aspartate-aminotransferase (ASAT) and alanine-aminotransferase (ALAT) ≤ 2.5 x upper reference range, in case of liver metastasis ≤ 5 x upper reference range
- Serum creatinine ≤ 1.5 x upper reference range
- Bilirubin ≤ 1.5 x upper reference range
- Negative pregnancy test for female and effective contraception for both male and female subjects if the risk of conception exists
- Signed written informed consent
Who cannot join
- Evidence for a mutation of the k-ras gene in the colorectal carcinoma cells
- Previous exposure to epidermal growth factor receptor-targeting therapy
- Prior chemotherapy for metastatic disease
- Prior oxaliplatin based adjuvant chemotherapy or < 6 months after end of adjuvant treatment
- Other previous malignancy with exception of a history of a previous curatively treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
- Radiotherapy, surgery (excluding prior diagnostic biopsy) or any investigational drug in the 30 days before registration
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- Concurrent chronic systemic immune therapy or hormone therapy not indicated in this study protocol
- Creatinine clearance < 30 ml/min
- Known hypersensitivity reaction to any of the components of study treatment
- Pregnancy (absence to be confirmed by ß-human chorionic gonadotropin (hCG) test) or lactation period
- Clinically relevant coronary artery disease, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia
- Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease
- Brain metastasis (known or suspected)
- Medical or psychological conditions that would not permit the subject to complete the study or sign informed consent
- Known alcohol or drug abuse
- Participation in another clinical study within the 30 days before registration
- Peripheral neuropathy > grade 1
- Significant disease which, in the investigator's opinion, would exclude the patient from the study
- Legal incapacity or limited legal capacity
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
University of Duisburg-Essen Medical School
Essen, North Rhine-Westphalia, 45122
Alfried Krupp von Bohlen und Halbach Krankenhaus gGmbH
Essen, North Rhine-Westphalia, 45131
Prosper Hospital Recklinghausen
Recklinghausen, North Rhine-Westphalia, 45659
About this study
Official title: Bi-weekly Cetuximab Combined With FOLFOX-6 as First-line Treatment in Metastatic Colorectal Cancer Patients With Wild-type K-ras Status
Cetuximab is normally given as a weekly schedule in the therapy of patients with metastatic colorectal cancer.
In order to improve the convenience for the patients in first line-therapy this study will evaluate the efficacy and safety of a bi-weekly combination of cetuximab with FOLFOX.
Read the detailed description
For years the effective treatment of advanced colorectal carcinoma (CRC) was limited to fluorouracil (5-FU). Combination of 5-FU or a 5-FU analog with oxaliplatin, which has some antitumor activity as a single agent, shows synergistic activity. Combining oxaliplatin with a twice monthly folinic acid/5-FU schedule leads to a further improvement in first-line treatment of advanced CRC thus emerging to a standard regimen in first-line therapy of metastatic CRC.
Cetuximab is normally given as a weekly schedule. As recently shown a biweekly schedule with 500 mg/m² instead of the weekly standard regimen (initial dose of 400 mg/m² followed by 250 mg/m² every week) exhibits similar pharmacokinetic results with a comparable efficacy.
In order to improve the convenience for the patients, this study will evaluate the efficacy and safety of a bi-weekly combination of cetuximab with FOLFOX. Out of the various FOLFOX regimens the most convenient FOLFOX-6 schedule is chosen for the study, which has been tested before in two studies in combination with the standard weekly schedule of cetuximab. Recent data suggest a decreased efficacy of cetuximab in patients bearing a k-ras mutation in their CRC. Therefore only patients with no evidence for a mutated k-ras gene in the colorectal carcinoma cells will be included in this study.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Cetuximab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
Also called Erbitux®
500 mg /m² cetuximab as an intravenous infusion over 120 minutes on day 1 every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Cetuximab + Folfox-6-regime | Experimental | Cetuximab 500 mg/m² administered as an intravenous infusion over 120 minutes on day 1 every 2 weeks. Combined with the following FOLFOX-6-regime:
Oxaliplatin 85 mg/m² i.v. for 2 h on day 1, Folinic acid 400 mg/m² i.v. for 2 h concurrently with Oxaliplatin on day 1, Fluorouracil 400 mg/m² i.v. bolus after Folinic Acid on day 1, followed by Fluorouracil 2400 mg/m² i.v. over 46 h. Receives: Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate (RECIST-Criteria)
Measured: Every 8 weeks
Secondary outcomes (1)
Secondary objectives: Safety, Quality of life
Measured: Every 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2010 (estimated)
- Study startFeb 2009
- Primary completionSep 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Martin Schuler, Prof. Dr. med.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Martin Schuler, Prof. Dr. med., Universität Duisburg-Essen
- Investigators
- Martin Schuler, Prof.Dr.med., Study director, University of Duisburg-Essen Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01051167
- Sponsor's protocol ID
- TT1-2007
- Other IDs
- 2007-000460-24
- Acronym
- CEBIFOX
- Status last verified
- May 2017
- First submitted
- 15 Jan 2010
- Last updated
- 8 May 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Kasper S, Meiler J, Knipp H, Hohler T, Reimer P, Steinmetz T, Berger W, Linden G, Reis H, Markus P, Paul A, Dechene A, Schumacher B, Kostbade K, Virchow I, Ting S, Worm K, Schmid KW, Herold T, Wiesweg M, Schuler M, Trarbach T. Biweekly Cetuximab Plus FOLFOX6 as First-Line Therapy in Patients With RAS Wild-Type Metastatic Colorectal Cancer: The CEBIFOX Trial. Clin Colorectal Cancer. 2020 Dec;19(4):236-247.e6. doi: 10.1016/j.clcc.2020.03.003. Epub 2020 Mar 19.
PubMed 32737003
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bi-weekly Cetuximab Combined With FOLFOX-6 as First-line Treatment in Metastatic Colorectal Cancer Patients With Wild-type K-ras Status
- ClinicalTrials.gov ID
- NCT01051167
- Acronym / sponsor ID
- CEBIFOX / TT1-2007
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Martin Schuler, Prof. Dr. med.University, hospital or other
- Study start
- Feb 2009
- Primary completion
- Sep 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 18 Jan 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cetuximab is normally given as a weekly schedule in the therapy of patients with metastatic colorectal cancer.
In order to improve the convenience for the patients in first line-therapy this study will evaluate the efficacy and safety of a bi-weekly combination of cetuximab with FOLFOX.
Detailed description
For years the effective treatment of advanced colorectal carcinoma (CRC) was limited to fluorouracil (5-FU). Combination of 5-FU or a 5-FU analog with oxaliplatin, which has some antitumor activity as a single agent, shows synergistic activity. Combining oxaliplatin with a twice monthly folinic acid/5-FU schedule leads to a further improvement in first-line treatment of advanced CRC thus emerging to a standard regimen in first-line therapy of metastatic CRC.
Cetuximab is normally given as a weekly schedule. As recently shown a biweekly schedule with 500 mg/m² instead of the weekly standard regimen (initial dose of 400 mg/m² followed by 250 mg/m² every week) exhibits similar pharmacokinetic results with a comparable efficacy.
In order to improve the convenience for the patients, this study will evaluate the efficacy and safety of a bi-weekly combination of cetuximab with FOLFOX. Out of the various FOLFOX regimens the most convenient FOLFOX-6 schedule is chosen for the study, which has been tested before in two studies in combination with the standard weekly schedule of cetuximab. Recent data suggest a decreased efficacy of cetuximab in patients bearing a k-ras mutation in their CRC. Therefore only patients with no evidence for a mutated k-ras gene in the colorectal carcinoma cells will be included in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cetuximab + Folfox-6-regime | Experimental | Drug: CetuximabCetuximab 500 mg/m² administered as an intravenous infusion over 120 minutes on day 1 every 2 weeks. Combined with the following FOLFOX-6-regime: Oxaliplatin 85 mg/m² i.v. for 2 h on day 1, Folinic acid 400 mg/m² i.v. for 2 h concurrently with Oxaliplatin on day 1, Fluorouracil 400 mg/m² i.v. bolus after Folinic Acid on day 1, followed by Fluorouracil 2400 mg/m² i.v. over 46 h. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histologically proven metastatic colorectal cancer
- Molecular test showing no mutation in the k-ras gene of colorectal carcinoma cells
- Male and female subjects ≥ 18 years of age
- 1st occurrence of metastatic disease (not curatively resectable)
- Life expectancy ≥ 12 weeks
Key exclusion criteria (19 listed)
- Evidence for a mutation of the k-ras gene in the colorectal carcinoma cells
- Previous exposure to epidermal growth factor receptor-targeting therapy
- Prior chemotherapy for metastatic disease
- Prior oxaliplatin based adjuvant chemotherapy or < 6 months after end of adjuvant treatment
- Other previous malignancy with exception of a history of a previous curatively treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CetuximabAlso: Erbitux®500 mg /m² cetuximab as an intravenous infusion over 120 minutes on day 1 every 2 weeks | Drug | Cetuximab + Folfox-6-regime |
Primary outcome
Response rate (RECIST-Criteria)
Time frame: Every 8 weeks
1 secondary outcome
Secondary objectives: Safety, Quality of life
Time frame: Every 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2017.
- Derived from this study: PubMed 32737003Kasper S, Meiler J, Knipp H, Hohler T, Reimer P, Steinmetz T, Berger W, Linden G, Reis H, Markus P, Paul A, Dechene A, Schumacher B, Kostbade K, Virchow I, Ting S, Worm K, Schmid KW, Herold T, Wiesweg M, Schuler M, Trarbach T. Biweekly Cetuximab Plus FOLFOX6 as First-Line Therapy in Patients With RAS Wild-Type Metastatic Colorectal Cancer: The CEBIFOX Trial. Clin Colorectal Cancer. 2020 Dec;19(4):236-247.e6. doi: 10.1016/j.clcc.2020.03.003. Epub 2020 Mar 19.
- Individual participant dataSharing planned: No
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CRC
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Schuler, Prof.Dr.med. study director
University of Duisburg-Essen Medical School
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cetuximab in people with Metastatic Colorectal Cancer, run by Martin Schuler, Prof. Dr. med. at 3 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response rate (RECIST-Criteria) (time frame: Every 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01051167, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2017.