EMD 525797 in Combination With Cetuximab and Irinotecan in K-ras Wildtype Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

— POSEIDON  

Official title:

An Open-label, Randomized, Controlled, Multicenter, Phase I/II Trial Investigating 2 EMD 525797 Doses in Combination With Cetuximab and Irinotecan Versus Cetuximab and Irinotecan Alone, as Second-line Treatment for Subjects With K-ras Wild Type Metastatic Colorectal Cancer.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01008475
• Other study ID #: EMR62242-004
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: October 19, 2009
• Last updated: August 7, 2015
• Start date: October 2009
• Est. completion date: April 2015

Study information

• Verified date: August 2015
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsCzech Republic: State Institute for Drug ControlGermany: Paul-Ehrlich-InstitutSpain: Spanish Agency of MedicinesUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics CommitteeRussia: Ministry of Health of the Russian FederationPoland: Ethics CommitteePoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsIsrael: Israeli Health Ministry Pharmaceutical AdministrationIsrael: Ministry of HealthHungary: National Institute of PharmacyHungary: Scientific and Medical Research Council Ethics CommitteeGreece: Ethics CommitteeGreece: National Organization of MedicinesCyprus: Cyprus National Bioethics CommitteeBulgaria: Bulgarian Drug AgencyBulgaria: Ethics committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety and clinical activity of the experimental drug EMD 525797 (study drug), a monoclonal antibody targeting α v integrins, in combination with irinotecan and cetuximab in K-ras wildtype metastatic colorectal cancer patients.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 229
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Subjects with histologically confirmed kras wildtype (WT) colorectal carcinoma (CRC) with documented distant metastasis;

• Prior oxaliplatin/fluoropyrimidine-containing regimen for the first-line treatment of metastatic disease;

• Failed an oxaliplatin regimen for metastatic colorectal carcinoma (mCRC). Failure is defined as either progressive disease (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 Response Evaluation Criteria In Solid Tumors (RECIST, Version 1.0), i.e., this lesion must be adequately measurable in at least 1 dimension (longest diameter to be recorded) as >=2 centimeter (cm) by conventional techniques or >=1 cm by spiral CT scan;

• Eastern Cooperative Oncology Group (ECOG) performance status 0 1, or KPS >=80%;

• Absolute Neutrophil Count(ANC) >=1.5 x 10^9/L;

• Platelets >=100 x 10^9/L;

• Hemoglobin >=9 g/dL (without transfusions);

• Bilirubin <=1.5 x ULN;

• ASAT <=5 x ULN and ALAT <=5 x ULN;

• Serum creatinine <=1.25 x Upper limit of normal (ULN) and/or creatinine clearance >=50 ml/min;

• International Nationalized Ratio (INR), and partial thromboplastin time (PTT) within normal limits;

• Sodium and potassium within normal limits or =10% above or below (supplementation permitted);

Exclusion Criteria:

• Previous treatment with any inhibitor of Epidermal Growth Factor Receptor (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), clinically relevant cardiomyopathy, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia;

• Uncontrolled hypertension defined as systolic blood pressure >=160 mmHg and/or diastolic blood pressure >=100 mmHg under resting conditions;

• History of coagulation disorder associated with bleeding or recurrent thrombotic events;

• History of recent peptic ulcer disease (endoscopically proven gastric, duodenal or esophageal ulcer) 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Biological:
• EMD 525797, Irinotecan and Cetuximab
Arm A: EMD 525797 (target dose: 500 mg) every 2 weeks + cetuximab 400 mg/m2, Day 1 Cycle 1, and afterwards 250 mg/m2 weekly + irinotecan 180 mg/m2 every 2 weeks
• EMD 525797, Irinotecan and Cetuximab
Arm B: EMD 525797 (target dose: 1,000 mg or as defined by SMC) every 2 weeks + cetuximab 400 mg/m2, Day 1 Cycle 1, and afterwards 250 mg/m2 weekly + irinotecan 180 mg/m2 every 2 weeks

Drug:
• Irinotecan and Cetuximab
Arm C: Cetuximab 400 mg/m2, Day 1 Cycle 1, and afterwards 250 mg/m2 weekly + irinotecan 180 mg/m2 every 2 weeks

Locations

Country	Name	City	State
Belgium	Research Site	Brussels
Belgium	Research Site	Edegem
Belgium	Research Site	Gent
Belgium	Research Site	Leuven
Bulgaria	Research Site	Sofia
Cyprus	Research Site	Strovolos	Nicosia
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Horovice
Czech Republic	Research Site	Kutna Hora
Czech Republic	Research Site	Olomouc
Czech Republic	Research Site	Pardubice
Czech Republic	Research Site	Prague
Germany	Research Site	Dresden
Germany	Research Site	Essen
Germany	Research Site	Freiburg
Germany	Research Site	Hamburg
Germany	Research site	Hannover
Germany	Research Site	Heilbronn
Germany	Research Site	Landshut
Germany	Research Site	Leipzig
Germany	Research Site	Munich
Germany	Research Site	Recklinghausen
Germany	Research Site	Ulm
Greece	Research Site	Mournies Chania
Greece	Research Site	Thessaloniki	Cyprus
Hungary	Research Site	Budapest
Hungary	Research Site	Gyor
Hungary	Research Site	Kecskemet
Hungary	Research Site	Miskolc
Hungary	Research Site	Nyiregyhaza
Hungary	Research Site	Szolnok
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Ramat Gan
Israel	Research Site	Rechovot
Israel	Research Site	Tel-Aviv
Poland	Research Site	Elblag
Poland	Research Site	Gdansk
Poland	Research Site	Gliwice
Poland	Research Site	Lódz
Poland	Research Site	Rybnik
Poland	Research Site	Warszawa
Russian Federation	Research	Arkhangelsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	Tomsk
Spain	Research Site	Barcelona
Spain	Research Site	Elche
Spain	Research Site	Madrid
Spain	Research Site	Mallorca
Spain	Research Site	Santander
Spain	Research Site	Santiago de Compostela
Spain	Research Site	Terrassa
Spain	Research Site	Valencia
United Kingdom	Research Site	Aberdeen
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Sutton

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Countries where clinical trial is conducted

Belgium,  Bulgaria,  Cyprus,  Czech Republic,  Germany,  Greece,  Hungary,  Israel,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary endpoint of Safety Part: Number and proportion of subjects experiencing DLTs (dose limiting toxicity) using the NCI-CTCAE Version 3.0 in each dose level over the first 2 weeks after first drug intake		the first 2 weeks after first drug intake (14 days)	Yes
Primary	Primary endpoint of Randomised Part: The Progression free survival (PFS) hazard ratio of each experimental treatment over standard of care arm.		Time from randomization until radiological progressive disease confirmed by investigator or all cause death	No
Secondary	To further evaluate the efficacy of 2 EMD 525797 doses with respect to overall survival (OS) time		Time from randomization to death	No
Secondary	To further evaluate the efficacy of 2 EMD 525797 doses with respect to time to progression (TTP)		Time from randomization to progression	No
Secondary	To further evaluate the efficacy of 2 EMD 525797 doses with respect to tumor response (RECIST criteria [Version 1.0])		Time from randomization to confirmed response	No
Secondary	To further evaluate the efficacy of 2 EMD 525797 doses with respect to time to treatment failure (TTF)		Time from randomization to treatment discontinuation for any reason	No