Subjects with k-ras WT, metastatic colorectal cancer who have failed a fist line chemotherapy with an oxaliplatin-containing regimen will be eligible for this trial. MedDRA version: 15.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: DI-17E6
Product Code: EMD 525797
Pharmaceutical Form: Solution for infusion
Current Sponsor code: EMD525797
Other descriptive name: DI-17E6
Concentration unit: mg/ml milligram(s)/millili
Sponsors
Merck KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed and dated written informed consent prior to any specific trial procedure and the ability to comply with the trial and follow-up procedures; • Age =18 years of male or female gender; • Subjects with histologically-confirmed k-ras WT CRC with documented distant metastasis; • Prior oxaliplatin/fluoropyrimidine-containing regimen for the first-line treatment of metastatic disease; • Failed an oxaliplatin regimen for metastatic disease. Failure is defined as either PD (clinical or radiologic) within 6 months of the last dose of any agent of an oxaliplatin-based regimen, or intolerance to an oxaliplatin regimen. Intolerance to an oxaliplatin regimen is defined as discontinuation due to any of the following: severe allergic reaction, persistent severe neurotoxicity, or delayed recovery from toxicity preventing retreatment; • At least 1 radiographically documented measurable lesion in a previously non-irradiated area according to RECIST (Version 1.0), i.e., this lesion must be adequately measurable in at least 1 dimension (longest diameter to be recorded) as =2 cm by conventional techniques or =1 cm by spiral CT scan; • ECOG performance status 0-1, or KPS =80%; • Acceptable laboratory parameters including ANC =1.5 x 10E9/L, platelets =100 x 109/L, hemoglobin =9 g/dL (without transfusions), bilirubin =1.5 x ULN, ASAT =5 x ULN, ALAT =5 x ULN, serum creatinine =1.25 x ULN and/or creatinine clearance =50 ml/min, PT, INR, and PTT within normal limits and sodium and potassium within normal limits or =10% above or below (supplementation permitted); • Effective contraception for both male and female subjects if the risk of conception exists. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Treatment in another clinical trial within the past 30 days or previous treatment with any inhibitor of EGFR; • Known brain metastasis and/or leptomeningeal disease; • Radiotherapy (except localized radiotherapy for pain relief), major surgery, or any investigational drug in the 30 days before the start of trial treatment entry, planned major surgery during the trial; • Concurrent chronic systemic immune or hormone therapy not indicated in this trial protocol (except for physiologic replacement; steroids up to 10 mg of prednisone equivalent or topical and inhaled steroids are allowed); • Clinically relevant coronary artery disease (New York Heart Association [NYHA] functional angina classification III/IV), congestive heart failure (NYHA III/IV), or clinically relevant cardiomyopathy; • Uncontrolled hypertension defined as systolic blood pressure =160 mmHg and/or diastolic blood pressure =100 mmHg under resting conditions; • History of myocardial infarction in the last 12 months, or a high risk of uncontrolled arrhythmia, coagulation disorder associated with bleeding or recurrent thrombotic events, recent peptic ulcer disease (endoscopically proven) within 6 months of trial treatment start, chronic inflammatory bowel disease, or acute/chronic ileus; • Active infection (requiring i.v. antibiotics), including active tuberculosis, active or chronic Hepatitis B or C, or ongoing HIV infection; • Presence of any contra-indications or known hypersensitivity to treatment with EMD 525797, cetuximab, and irinotecan, or to any of the excipients of these drugs; • Pregnancy or lactation period; • Concurrent treatment with a non-permitted drug; • Previous malignancy other than CRC in the last 5 years except for basal cell cancer of the skin or pre-invasive cancer of the cervix; • Medical or psychological conditions that would not permit the subject to complete the trial or sign informed consent; • Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who are suffering or have suffered from such; • Legal incapacity or limited legal capacity; • Significant disease which, in the Investigator’s opinion, would exclude the subject from the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives are: • To characterize the safety and tolerability profile of repeated administration of different EMD 525797 dose levels in combination with cetuximab and irinotecan in subjects with k-ras WT mCRC after failure of first-line therapy with an oxaliplatin-containing regimen (Safety Part); • To assess the anti-cancer activity of 2 EMD 525797 doses in terms progression-free survival time in subjects with k-ras WT mCRC after failure of first-line therapy with an oxaliplatin-containing regimen (Randomized Part). ;Secondary Objective: The secondary objectives are to: • Further evaluate the efficacy of 2 EMD 525797 doses with respect to Overall survival (OS) time, Time to tumor progression (TTP), tumor response (RECIST criteria [Version 1.0]), and Time to treatment failure (TTF); • Evaluate the pharmacokinetic (PK) profile of EMD 525797 and its effects on cetuximab as well as the PK profile of cetuximab and its effect on EMD 525797.;Primary end point(s): Safety Part: • To characterize the safety and tolerability profile of repeated administration of different EMD 525797 dose levels in combination with cetuximab and irinotecan in subjects with k-ras WT mCRC after failure of first-line therapy with an oxaliplatin-containing regimen. Randomized Part: • To assess the anti-cancer activity of 2 EMD 525797 doses in terms of progression-free survival time in subjects with k-ras WT mCRC after failure of first-line therapy with an oxaliplatin-containing regimen.;Timepoint(s) of evaluation of this end point: After 173 events have been observed | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of the trial are OS time, TTP, TTF, Tumor Response, Disease Control, safety, and tolerability;Timepoint(s) of evaluation of this end point: After 173 events have been observed | — |
Countries
Belgium, Bulgaria, Czech Republic, Germany, Greece, Hungary, Israel, Poland, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactCommunication Centre Merck KGaA
Merck KGaA
Outcome results
None listed