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

NCT ID: NCT01008475

Last Updated: 2016-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 232 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2015-04-30

Brief 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 alfa integrins, in combination with irinotecan and cetuximab in K-ras wildtype metastatic colorectal cancer patients.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Safety part: EMD 525797 250 mg + Standard of Care (SoC)

EMD 525797 250 mg in combination with cetuximab and irinotecan

Group Type: EXPERIMENTAL

EMD 525797 250 mg

Intervention Type: DRUG

EMD 525797 will be administered at a target dose of 250 mg as a 1-hour intravenous infusion for every 2 week until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Cetuximab

Intervention Type: DRUG

Safety part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until DLT.

Randomized part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Irinotecan

Intervention Type: DRUG

Safety part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Randomized part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Safety part: EMD 525797 500 mg + SoC

EMD 525797 500 mg in combination with cetuximab and irinotecan

Group Type: EXPERIMENTAL

EMD 525797 500 mg

Intervention Type: DRUG

Safety part: EMD 525797 will be administered at a target dose of 500 mg as a 1-hour intravenous infusion for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Randomized part: EMD 525797 will be administered at a target dose of 500 mg as a 1-hour intravenous infusion for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Cetuximab

Intervention Type: DRUG

Safety part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until DLT.

Randomized part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Irinotecan

Intervention Type: DRUG

Safety part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Randomized part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Safety part: EMD 525797 750 mg + SoC

EMD 525797 750 mg in combination with cetuximab and irinotecan

Group Type: EXPERIMENTAL

EMD 525797 750 mg

Intervention Type: DRUG

EMD 525797 will be administered at a target dose of 750 mg as a 1-hour intravenous infusion for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Cetuximab

Intervention Type: DRUG

Safety part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until DLT.

Randomized part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Irinotecan

Intervention Type: DRUG

Safety part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Randomized part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Safety part: EMD 525797 1000 mg + SoC

EMD 525797 1000 mg in combination with cetuximab and irinotecan

Group Type: EXPERIMENTAL

EMD 525797 1000 mg

Intervention Type: DRUG

Safety part: EMD 525797 will be administered at a target dose of 1000 mg as a 1-hour intravenous infusion for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Randomized part: EMD 525797 will be administered at a target dose of 1000 mg as a 1-hour intravenous infusion for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Cetuximab

Intervention Type: DRUG

Safety part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until DLT.

Randomized part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Irinotecan

Intervention Type: DRUG

Safety part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Randomized part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Randomized part: EMD 525797 500 mg + SoC

EMD 525797 500 mg in combination with cetuximab and irinotecan

Group Type: EXPERIMENTAL

EMD 525797 500 mg

Intervention Type: DRUG

Safety part: EMD 525797 will be administered at a target dose of 500 mg as a 1-hour intravenous infusion for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Randomized part: EMD 525797 will be administered at a target dose of 500 mg as a 1-hour intravenous infusion for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Cetuximab

Intervention Type: DRUG

Safety part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until DLT.

Randomized part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Irinotecan

Intervention Type: DRUG

Safety part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Randomized part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Randomized Part: EMD 525797 1000 mg + SoC

EMD 525797 1000 mg (or dose as defined by safety monitoring committee (SMC)\] in combination with cetuximab and irinotecan.

Group Type: EXPERIMENTAL

EMD 525797 1000 mg

Intervention Type: DRUG

Safety part: EMD 525797 will be administered at a target dose of 1000 mg as a 1-hour intravenous infusion for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Randomized part: EMD 525797 will be administered at a target dose of 1000 mg as a 1-hour intravenous infusion for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Cetuximab

Intervention Type: DRUG

Safety part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until DLT.

Randomized part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Irinotecan

Intervention Type: DRUG

Safety part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Randomized part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Randomized Part: SoC

Cetuximab and irinotecan

Group Type: OTHER

Cetuximab

Intervention Type: DRUG

Safety part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until DLT.

Randomized part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Irinotecan

Intervention Type: DRUG

Safety part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Randomized part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Interventions

EMD 525797 250 mg

EMD 525797 will be administered at a target dose of 250 mg as a 1-hour intravenous infusion for every 2 week until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Intervention Type: DRUG

EMD 525797 500 mg

Safety part: EMD 525797 will be administered at a target dose of 500 mg as a 1-hour intravenous infusion for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Randomized part: EMD 525797 will be administered at a target dose of 500 mg as a 1-hour intravenous infusion for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Intervention Type: DRUG

EMD 525797 750 mg

EMD 525797 will be administered at a target dose of 750 mg as a 1-hour intravenous infusion for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Intervention Type: DRUG

EMD 525797 1000 mg

Safety part: EMD 525797 will be administered at a target dose of 1000 mg as a 1-hour intravenous infusion for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Randomized part: EMD 525797 will be administered at a target dose of 1000 mg as a 1-hour intravenous infusion for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Intervention Type: DRUG

Cetuximab

Safety part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until DLT.

Randomized part: Cetuximab will be administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Intervention Type: DRUG

Irinotecan

Safety part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent .

Randomized part: Irinotecan will be administered at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator's assessment), or withdrawal of consent.

Intervention Type: DRUG

Other Intervention Names

Abituzumab; Abituzumab

Eligibility Criteria

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 greater than or equal to (>=) 2 centimeter (cm) by conventional techniques or >=1 cm by spiral computed tomography (CT) scan
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, or Karnofsky performance status (KPS) >= 80 percent (%)
• Absolute Neutrophil Count (ANC) >=1.5 x 10^9/Liter
• Platelets >=100 x 10^9/Liter
• Hemoglobin >=9 gram per deciliter (g/dL) (without transfusions)
• Bilirubin less than or equal to (<=) 1.5 x upper limit normal (ULN)
• Aspartate transaminase (AST) <=5 x ULN and alanine transaminase (ALT) <=5 x ULN
• Serum creatinine <=1.25 x ULN and/or creatinine clearance >=50 milliliter per minute (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 millimeter of mercury (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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Prof. Josep Tabernero

Role: PRINCIPAL_INVESTIGATOR

HU Vall d' Hebron, Servei d'oncologia. E difici General

Locations

Research Site

Brussels, , Belgium

Research Site

Edegem, , Belgium

Research Site

Ghent, , Belgium

Research Site

Leuven, , Belgium

Research Site

Sofia, , Bulgaria

Research Site

Stróvolos, Nicosia, Cyprus

Research Site

Brno, , Czechia

Research Site

Hořovice, , Czechia

Research Site

Kutná Hora, , Czechia

Research Site

Olomouc, , Czechia

Research Site

Pardubice, , Czechia

Research Site

Prague, , Czechia

Research Site

Dresden, , Germany

Research Site

Essen, , Germany

Research Site

Freiburg im Breisgau, , Germany

Research Site

Hamburg, , Germany

Research site

Hanover, , Germany

Research Site

Heilbronn, , Germany

Research Site

Landshut, , Germany

Research Site

Leipzig, , Germany

Research Site

Munich, , Germany

Research Site

Recklinghausen, , Germany

Research Site

Ulm, , Germany

Research Site

Thessaloniki, Cyprus, Greece

Research Site

Mournies Chania, , Greece

Research Site

Budapest, , Hungary

Research Site

Győr, , Hungary

Research Site

Kecskemét, , Hungary

Research Site

Miskolc, , Hungary

Research Site

Nyíregyháza, , Hungary

Research Site

Szolnok, , Hungary

Research Site

Haifa, , Israel

Research Site

Jerusalem, , Israel

Research Site

Ramat Gan, , Israel

Research Site

Rehovot, , Israel

Research Site

Tel Aviv, , Israel

Research Site

Elblag, , Poland

Research Site

Gdansk, , Poland

Research Site

Gliwice, , Poland

Research Site

Lodz, , Poland

Research Site

Rybnik, , Poland

Research Site

Warsaw, , Poland

Research

Arkhangelsk, , Russia

Research Site

Moscow, , Russia

Research Site

Novosibirsk, , Russia

Research Site

Omsk, , Russia

Research Site

Saint Petersburg, , Russia

Research Site

Tomsk, , Russia

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, , Spain

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, , United Kingdom

Countries

Belgium; Bulgaria; Cyprus; Czechia; Germany; Greece; Hungary; Israel; Poland; Russia; Spain; United Kingdom

References

Elez E, Kocakova I, Hohler T, Martens UM, Bokemeyer C, Van Cutsem E, Melichar B, Smakal M, Csoszi T, Topuzov E, Orlova R, Tjulandin S, Rivera F, Straub J, Bruns R, Quaratino S, Tabernero J. Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial. Ann Oncol. 2015 Jan;26(1):132-140. doi: 10.1093/annonc/mdu474. Epub 2014 Oct 15.

Reference Type: DERIVED

PMID: 25319061 (View on PubMed)

Other Identifiers

EMR62242-004

Identifier Type: -

Identifier Source: org_study_id