Metastatic Colorectal CancerPhase 1/2APECNCT00778830
Study Evaluating the Safety and Efficacy of FOLFIRI Plus Cetuximab or FOLFOX Plus Cetuximab as First-line Therapy in Subjects With KRAS Wild-type Metastatic Colorectal Cancer (APEC-Study)
A Phase 1/2 study testing Cetuximab, FOLFIRI and FOLFOX in people with Metastatic Colorectal Cancer, run by Merck KGaA, Darmstadt, Germany at 1 site in Singapore.
Trial summary
This is an open-label, non-randomized, multicenter Phase II study evaluating folinic acid + fluorouracil + irinotecan (FOLFIRI) plus cetuximab (Erbitux) or folinic acid + fluorouracil + oxaliplatin (FOLFOX) plus cetuximab as first-line therapy of patients with KRAS wild-type metastatic colorectal cancer. 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, FOLFIRI and FOLFOX
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 289 participants
- Where
- 1 siteSingapore
- Study dates
- Feb 2009to Apr 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Signed written informed consent
- Inpatient or outpatient subjects, 18 years of age
- Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum
- Metastatic disease (M1)
- Life expectancy of at least 12 weeks
- Presence of at least 1 measurable index lesion (not lie in an irradiated area) by computed tomography (CT) scan or magnetic resonance imaging (MRI)
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- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry
- Effective contraception for both male and female subjects if the risk of conception exists
- White blood cell count greater than or equal to (>=) 3,000 per cubic millimeter (/mm^3) with neutrophils >=1,500/mm3, platelet count >=100,000/mm3, hemoglobin >=5.6 millimole per liter (mmol/L) (9 gram per deciliter [g/dL])
- Total bilirubin less than or equal to (<=) 1.5 x upper reference range
- Aspartate aminotransferase (AST) <=2.5 x upper reference range, or <=5 x upper reference range in case of liver metastasis
- Serum creatinine <=1.5 x upper reference range
- Recovery from relevant toxicity to previous treatment before study entry
- KRAS wild-type status of tumor tissue
Who cannot join
- Previous chemotherapy for colorectal cancer except adjuvant treatment if terminated >6 months before the start of treatment in this study
- Radiotherapy, surgery (excluding prior diagnostic biopsy) or any investigational drug in the 30 days before the start of treatment in this study
- Concurrent chronic systemic immune therapy, targeted therapy, anti-vascular endothelial growth factor (VEGF) therapy, or epidermal growth factor receptor (EGFR-) pathway targeting therapy not indicated in this study protocol
- Concurrent hormone therapy not indicated in this study protocol except for physiologic replacement or contraception
- Known hypersensitivity reaction to any of the components of study treatments
- Pregnancy (absence to be confirmed by beta human choriongonadotrophin [beta-hCG] test) or lactation period
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- Brain metastasis and/or leptomeningeal disease (known or suspected)
- 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
- Peripheral neuropathy > grade 1
- Previous malignancy other than colorectal cancer in the last 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix
- Known alcohol or drug abuse
- Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent
- Participation in another clinical study within the past 30 days
- Significant disease which, in the investigator's opinion, would exclude the patient from the study
- Legal incapacity or limited legal capacity
- KRAS mutated status of tumor tissue
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Asia Pacific Non-randomized, Open-label Phase II Study Evaluating the Safety and Efficacy of FOLFIRI Plus Cetuximab (Erbitux) or FOLFOX Plus Cetuximab as First-line Therapy in Subjects With KRAS Wild-type Metastatic Colorectal Cancer (APEC-Study)
This is an open-label, non-randomized, multicenter Phase II study evaluating folinic acid + fluorouracil + irinotecan (FOLFIRI) plus cetuximab (Erbitux) or folinic acid + fluorouracil + oxaliplatin (FOLFOX) plus cetuximab as first-line therapy of patients with KRAS wild-type metastatic colorectal cancer.
Only subjects with k-ras oncogene (KRAS) wild-type tumors are eligible. Efficacy will be assessed every 8 weeks. Treatment will be continued until progressive disease or unacceptable adverse events occur. After the end of study treatment, information on further anticancer treatment and survival will be collected every 3 months.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Cetuximab, FOLFIRI, FOLFOX
- Keywords
- mCRC
- 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
Cetuximab will be administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.
FOLFIRIDrug
Irinotecan will be administered intravenously at a dose of 180 mg/m^2 along with folinic acid administration intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form) and 5-fluorouracil will be administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion of 2,400 mg/m^2 given biweekly until disease progression, death, or consent withdrawal.
FOLFOXDrug
Oxaliplatin will be administered intravenously at a dose of 100 mg/m^2 along with folinic acid administration intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form) and 5-fluorouracil administration intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion of 2,400 mg/m^2 given biweekly until disease progression, death, or consent withdrawal.
| Study group | Role | What they receive |
|---|---|---|
| Cetuximab plus FOLFIRI | Experimental | Not described Receives: Drug: Cetuximab; Drug: FOLFIRI |
| Cetuximab plus FOLFOX | Experimental | Not described Receives: Drug: Cetuximab; Drug: FOLFOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Subjects With Best Overall Confirmed Response Rate (BORR)
Response rate was defined as the percentage of subjects with BORR (confirmed complete response [CR] or partial response [PR]) according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. As per RECIST v 1.0 criteria for target lesions and assessed by magnetic resonance imaging (MRI): CR = disappearance of all target lesions; PR = at least 30 percent (%) decrease in the sum of the longest diameter of target lesions. Response rate will be assessed every 8 weeks.
Measured: From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited until data cut-off date (31 May 2012)
Secondary outcomes (3)
Progression-Free Survival (PFS) Time
PFS time was defined as the time from first administration of study drug until first observation of disease progression or death when death occurs within 90 days of the last tumor assessment or first study drug dose whichever occurred.
Measured: From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014)
Overall Survival (OS) Time
OS time was defined as the time from first administration of study drug until date of death, assessed up to 5 years. OS time was censored if the subject was found to be alive on the last date of the assessment.
Measured: From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014)
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and TEAEs Leading to Death
An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Measured: From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2008 (estimated)
- Study startFeb 2009
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 289 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Pte. Ltd., Singapore
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck Pte. Ltd., Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00778830
- Sponsor's protocol ID
- EMR 62202-505
- Acronym
- APEC
- Status last verified
- Apr 2015
- First submitted
- 22 Oct 2008
- Last updated
- 14 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Asia Pacific Non-randomized, Open-label Phase II Study Evaluating the Safety and Efficacy of FOLFIRI Plus Cetuximab (Erbitux) or FOLFOX Plus Cetuximab as First-line Therapy in Subjects With KRAS Wild-type Metastatic Colorectal Cancer (APEC-Study)
- ClinicalTrials.gov ID
- NCT00778830
- Acronym / sponsor ID
- APEC / EMR 62202-505
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- mCRC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 289 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Collaborators
- Merck Pte. Ltd., Singapore
- Study start
- Feb 2009
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 23 Oct 2008 (estimated)
- Results
- Posted 14 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, non-randomized, multicenter Phase II study evaluating folinic acid + fluorouracil + irinotecan (FOLFIRI) plus cetuximab (Erbitux) or folinic acid + fluorouracil + oxaliplatin (FOLFOX) plus cetuximab as first-line therapy of patients with KRAS wild-type metastatic colorectal cancer.
Only subjects with k-ras oncogene (KRAS) wild-type tumors are eligible. Efficacy will be assessed every 8 weeks. Treatment will be continued until progressive disease or unacceptable adverse events occur. After the end of study treatment, information on further anticancer treatment and survival will be collected every 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cetuximab plus FOLFIRI | Experimental | Drug: Cetuximab, Drug: FOLFIRI |
| Cetuximab plus FOLFOX | Experimental | Drug: Cetuximab, Drug: FOLFOX |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Signed written informed consent
- Inpatient or outpatient subjects, 18 years of age
- Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum
- Metastatic disease (M1)
- Life expectancy of at least 12 weeks
Key exclusion criteria (17 listed)
- Previous chemotherapy for colorectal cancer except adjuvant treatment if terminated >6 months before the start of treatment in this study
- Radiotherapy, surgery (excluding prior diagnostic biopsy) or any investigational drug in the 30 days before the start of treatment in this study
- Concurrent chronic systemic immune therapy, targeted therapy, anti-vascular endothelial growth factor (VEGF) therapy, or epidermal growth factor receptor (EGFR-) pathway targeting therapy not indicated in this study protocol
- Concurrent hormone therapy not indicated in this study protocol except for physiologic replacement or contraception
- Known hypersensitivity reaction to any of the components of study treatments
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: ErbituxCetuximab will be administered intravenously at a dose of 500 milligram per square meter (mg/m^2) biweekly on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent. | Drug | Cetuximab plus FOLFIRI, Cetuximab plus FOLFOX |
| FOLFIRIIrinotecan will be administered intravenously at a dose of 180 mg/m^2 along with folinic acid administration intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form) and 5-fluorouracil will be administered intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion of 2,400 mg/m^2 given biweekly until disease progression, death, or consent withdrawal. | Drug | Cetuximab plus FOLFIRI |
| FOLFOXOxaliplatin will be administered intravenously at a dose of 100 mg/m^2 along with folinic acid administration intravenously at a dose of 400 mg/m^2 (racemic) or 200 mg/m^2 (L-form) and 5-fluorouracil administration intravenously at a dose of 400 mg/m^2 bolus followed by a 46-hour continuous infusion of 2,400 mg/m^2 given biweekly until disease progression, death, or consent withdrawal. | Drug | Cetuximab plus FOLFOX |
Primary outcome
Percentage of Subjects With Best Overall Confirmed Response Rate (BORR)
Time frame: From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited until data cut-off date (31 May 2012)
Response rate was defined as the percentage of subjects with BORR (confirmed complete response [CR] or partial response [PR]) according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. As per RECIST v 1.0 criteria for target lesions and assessed by magnetic resonance imaging (MRI): CR = disappearance of all target lesions; PR = at least 30 percent (%) decrease in the sum of the longest diameter of target lesions. Response rate will be assessed every 8 weeks.
3 secondary outcomes
Progression-Free Survival (PFS) Time
Time frame: From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014)
Overall Survival (OS) Time
Time frame: From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014)
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and TEAEs Leading to Death
Time frame: From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Medical Responsible study director
Merck Pte. Ltd., Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cetuximab, FOLFIRI and FOLFOX in people with Metastatic Colorectal Cancer, run by Merck KGaA, Darmstadt, Germany at 1 site in Singapore.
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 17 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 14 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 14 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Subjects With Best Overall Confirmed Response Rate (BORR) (time frame: From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited until data cut-off date (31 May 2012)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 May 2015.