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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) (APEC)

Primary Purpose

Metastatic Colorectal Cancer

Status
Completed
Phase
Phase 1
Locations
Singapore
Study Type
Interventional
Intervention
Cetuximab
FOLFIRI
FOLFOX
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring mCRC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cetuximab plus FOLFIRI

Cetuximab plus FOLFOX

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
October 22, 2008
Last Updated
April 28, 2015
Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Pte. Ltd., Singapore
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1. Study Identification

Unique Protocol Identification Number
NCT00778830
Brief Title
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)
Acronym
APEC
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

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Pte. Ltd., Singapore

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
mCRC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
289 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cetuximab plus FOLFIRI
Arm Type
Experimental
Arm Title
Cetuximab plus FOLFOX
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
FOLFIRI
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
FOLFOX
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Subjects With Best Overall Confirmed Response Rate (BORR)
Description
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.
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)
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS) Time
Description
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.
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)
Title
Overall Survival (OS) Time
Description
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.
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)
Title
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and TEAEs Leading to Death
Description
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.
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck Pte. Ltd., Singapore
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Singapore
Country
Singapore

12. IPD Sharing Statement

Learn more about this trial

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)

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