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)

NCT00778830 | Completed Phase 1 Results

• 1 other identifier: EMR 62202-505
• Study Type: interventional
• Target: 289
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Colorectal Cancer

Keywords

mCRC

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  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

  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)

Study Arms (2)

Cetuximab plus FOLFIRI

EXPERIMENTAL

Drug: Cetuximab; Drug: FOLFIRI

Cetuximab plus FOLFOX

EXPERIMENTAL

Drug: Cetuximab; Drug: FOLFOX

Interventions

Cetuximab DRUG

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.

Also known as: Erbitux

Cetuximab plus FOLFIRI; Cetuximab plus FOLFOX

FOLFIRI DRUG

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.

Cetuximab plus FOLFIRI

FOLFOX DRUG

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.

Cetuximab plus FOLFOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead
• Merck Pte. Ltd., Singapore: collaborator

Study Sites (1)

Research Site

Singapore, Singapore

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; IFL protocol; Folfox protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Pte. Ltd., Singapore

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2008
• First Posted: October 23, 2008
• Study Start: February 1, 2009
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: May 14, 2015
• Results First Posted: May 14, 2015

Record last verified: 2015-04

Locations

SG (1)