E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052362 |
E.1.2 | Term | Metastatic colorectal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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).
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
to characterize the safety and tolerability profile |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
there is no real comparator as it is a add on design |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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An updated efficacy evaluation will be provided after 173 subjects experienced death or disease progression. The trial will end when both conditions will apply: • all subjects have received the last dose of trial treatment (including 28 days of safety follow-up and the EOT Visit) • 2/3 of the subjects have experienced death |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |