Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01008475
Recruitment Status : Completed
First Posted : November 5, 2009
Results First Posted : March 30, 2016
Last Update Posted : March 30, 2016
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: EMD 525797 250 mg Drug: EMD 525797 500 mg Drug: EMD 525797 750 mg Drug: EMD 525797 1000 mg Drug: Cetuximab Drug: Irinotecan Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 232 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : October 2009
Actual Primary Completion Date : April 2015
Actual Study Completion Date : April 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Safety part: EMD 525797 250 mg + Standard of Care (SoC)
EMD 525797 250 mg in combination with cetuximab and irinotecan
Drug: 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 .

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.


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.


Experimental: Safety part: EMD 525797 500 mg + SoC
EMD 525797 500 mg in combination with cetuximab and irinotecan
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.


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.


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.


Experimental: Safety part: EMD 525797 750 mg + SoC
EMD 525797 750 mg in combination with cetuximab and irinotecan
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 .
Other Name: Abituzumab

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.


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.


Experimental: Safety part: EMD 525797 1000 mg + SoC
EMD 525797 1000 mg in combination with cetuximab and irinotecan
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.

Other Name: Abituzumab

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.


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.


Experimental: Randomized part: EMD 525797 500 mg + SoC
EMD 525797 500 mg in combination with cetuximab and irinotecan
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.


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.


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.


Experimental: 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.
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.

Other Name: Abituzumab

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.


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.


Randomized Part: SoC
Cetuximab and irinotecan
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.


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.





Primary Outcome Measures :
  1. Safety Part: Number of Subjects Experiencing DLTs (Dose Limiting Toxicity) [ Time Frame: Time from the first dose of study drug up to 2 weeks ]
    DLT was defined as any Grade 4 hematologic toxicity or Grade 3/4 non-hematologic toxicity assessed as related to trial treatment by the Investigator and/or Sponsor and confirmed by the safety monitoring committee (SMC) to be relevant to the combination treatment within the first cycle of therapy. Any Grade 3 or 4 non haematological toxicity, any Grade 4 hematological toxicity, treatment related deaths within the first 2 weeks of therapy. Toxicities excluded from DLT: alopecia, rash, nausea, vomiting and hypomagnesemia of Grade 3 or 4 severity, Grade 4 neutropenia or leukopenia lasting for =< 5 days and not associated with fever; Single laboratory values out of normal range without any clinical correlation and resolve within 7 days; Grade 3 or 4 diarrhoea without adequate supportive care. Adequate supportive care has been administered and Grade 4 diarrhea persists (investigator decision); isolated Grade 4 lymphocytopenia and thrombocytopenia without clinical correlation.

  2. Randomized Part: Progression Free Survival (PFS) [ Time Frame: Time from randomization until progressive disease or death; assessed up to 18 months (i.e data cut-off date: 09 Oct 2013) ]
    PFS was defined as the time from the randomization date to first documented sign of objective radio-graphic disease progression (PD) as per Response Evaluation Criteria In Solid Tumors version 1. (RECIST 1.0) or death from any cause if reported within 12 weeks from the last tumor assessment. PD per RECIST v 1.0 was defined as at least 20% increase in the sum of the longest diameter of target lesions, taking as the reference the smallest sum of longest diameters recorded since treatment started, or unequivocal progression of existing non-target lesion or appearance of new lesions. Subjects who did not progress or died at the time of analyses, or subjects who died without previously radio-graphically documented PD and death was observed after more than 12 weeks of last tumor assessment without progression, these subjects were censored at their last tumor assessment date or date of randomization, whichever occurred last.


Secondary Outcome Measures :
  1. Overall Survival (OS) Time [ Time Frame: Time from randomization until death assessed up to 18 months (i.e data cut-off date: 09 Oct 2013) ]
    OS was defined as the time from the date of randomization to the date of death from any cause. For subjects who were still alive at the analysis cut off date or lost to follow up, survival was censored at the last recorded date the subject was known to be alive or at the analysis cut off date, whichever occurred first.

  2. Time to Progression (TTP) [ Time Frame: Time from randomization until disease progression assessed up to 18 months (i.e data cut-off date: 09 Oct 2013) ]
    TTP was defined as the time from the date of randomization to the date of objective radiographic disease progression (PD). PD per RECIST v 1.0 was defined as at least 20% increase in the sum of the longest diameter of target lesions, taking as the reference the smallest sum of longest diameters recorded since treatment started, or unequivocal progression of existing non-target lesion or appearance of new lesions. For subjects who did not progress or who were without any post baseline tumor assessment, TTP was censored at their last tumor assessment date, or at the randomization date, whichever occurred last.

  3. Number of Subjects With Tumor Response [ Time Frame: Time from randomization up to 18 months (i.e data cut-off date: 09 Oct 2013) ]
    Tumor response was defined as the presence of at least 1 confirmed complete response (CR) or confirmed partial response (PR) as judged by RECIST version 1.0. CR was defined for target lesions (TLs) as the disappearance of all lesions, and for non-target lesions (NTLs) as the disappearance of all non-target non-measurable lesions and/or normalization of serum levels of tumor markers. PR was defined for TLs as at least a 30 percent (%) decrease from baseline (BL) in the sum of longest diameter (SLD) of TLs.

  4. Time to Treatment Failure (TTF) [ Time Frame: Time from randomization until discontinuation assessed up to 18 months (i.e data cut-off date: 09 Oct 2013) ]
    TTF was defined as the time from randomization to treatment discontinuation for any reason. For subjects on drug at the analysis cut off date or lost to follow up, TTF was censored at the trial discontinuation date or at the analysis cut off date, whichever occurred first.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01008475


  Show 62 Study Locations
Sponsors and Collaborators
Merck KGaA, Darmstadt, Germany
Investigators
Layout table for investigator information
Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany
Principal Investigator: Prof. Josep Tabernero HU Vall d' Hebron, Servei d'oncologia. E difici General

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT01008475     History of Changes
Other Study ID Numbers: EMR62242-004
First Posted: November 5, 2009    Key Record Dates
Results First Posted: March 30, 2016
Last Update Posted: March 30, 2016
Last Verified: February 2016

Keywords provided by Merck KGaA, Darmstadt, Germany:
EMD 525797
Cetuximab
Irinotecan
metastatic colorectal cancer

Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Cetuximab
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Immunological