Clinical trial NCT00778830: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: mCRC
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
Collaborators: name: Merck Pte. Ltd., Singapore
First posted: 2008-10-23
Enrollment: 289
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.


Eligibility criteria: Inclusion Criteria:

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)
* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Percentage of Subjects With Best Overall Confirmed Response Rate (BORR)
timeFrame: 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:
measure: Progression-Free Survival (PFS) Time
timeFrame: 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)
measure: Overall Survival (OS) Time
timeFrame: 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)
measure: Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and TEAEs Leading to Death
timeFrame: 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)
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Research Site
Study officials:
affiliation: Merck Pte. Ltd., Singapore
name: Medical Responsible
role: STUDY_DIRECTOR
References: