Clinical trial NCT01008475: EMD 525797 in Combination With Cetuximab and Irinotecan in K-ras Wild Type Metastatic Colorectal Cancer
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 (mCRC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: EMD 525797
Cetuximab
Irinotecan
metastatic colorectal cancer
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2009-11-05
Enrollment: 232
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Safety Part: Number of Subjects Experiencing DLTs (Dose Limiting Toxicity)
timeFrame: Time from the first dose of study drug up to 2 weeks
measure: Randomized Part: Progression Free Survival (PFS)
timeFrame: Time from randomization until progressive disease or death; assessed up to 18 months (i.e data cut-off date: 09 Oct 2013)
Secondary outcomes:
measure: Overall Survival (OS) Time
timeFrame: Time from randomization until death assessed up to 18 months (i.e data cut-off date: 09 Oct 2013)
measure: Time to Progression (TTP)
timeFrame: Time from randomization until disease progression assessed up to 18 months (i.e data cut-off date: 09 Oct 2013)
measure: Number of Subjects With Tumor Response
timeFrame: Time from randomization up to 18 months (i.e data cut-off date: 09 Oct 2013)
measure: Time to Treatment Failure (TTF)
timeFrame: Time from randomization until discontinuation assessed up to 18 months (i.e data cut-off date: 09 Oct 2013)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Research Site
city: Edegem
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Strovolos
country: Cyprus
facility: Research Site
state: Nicosia
city: Brno
country: Czech Republic
facility: Research Site
city: Horovice
country: Czech Republic
facility: Research Site
city: Kutna Hora
country: Czech Republic
facility: Research Site
city: Olomouc
country: Czech Republic
facility: Research Site
city: Pardubice
country: Czech Republic
facility: Research Site
city: Prague
country: Czech Republic
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Freiburg
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research site
city: Heilbronn
country: Germany
facility: Research Site
city: Landshut
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Munich
country: Germany
facility: Research Site
city: Recklinghausen
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
state: Cyprus
city: Mournies Chania
country: Greece
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Gyor
country: Hungary
facility: Research Site
city: Kecskemet
country: Hungary
facility: Research Site
city: Miskolc
country: Hungary
facility: Research Site
city: Nyiregyhaza
country: Hungary
facility: Research Site
city: Szolnok
country: Hungary
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Rechovot
country: Israel
facility: Research Site
city: Tel-Aviv
country: Israel
facility: Research Site
city: Elblag
country: Poland
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Gliwice
country: Poland
facility: Research Site
city: Rybnik
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Arkhangelsk
country: Russian Federation
facility: Research
city: Moscow
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Tomsk
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Elche
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Mallorca
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
facility: Research Site
city: Terrassa
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Aberdeen
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
affiliation: HU Vall d' Hebron, Servei d'oncologia. E difici General
name: Prof. Josep Tabernero
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.