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Sym004 in Combination With FOLFIRI in Metastatic Colorectal Cancer Patients

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ClinicalTrials.gov Identifier: NCT02568046
Recruitment Status : Terminated (Discontinued development of Sym004 in combination with FOLFIRI)
First Posted : October 5, 2015
Results First Posted : January 9, 2019
Last Update Posted : March 26, 2019
Sponsor:
Information provided by (Responsible Party):
Symphogen A/S

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Colorectal Cancer
Interventions Drug: Sym004
Drug: FOLFIRI
Enrollment 10
Recruitment Details The first patient was enrolled in March 2016. In January 2017, the trial was terminated early and enrollment was prematurely discontinued.
Pre-assignment Details  
Arm/Group Title Dose Level 1: Sym004 12 mg/kg + FOLFIRI Dose Level -1: Sym004 9 mg/kg + FOLFIRI
Hide Arm/Group Description

Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR).

The standard FOLFIRI regimen consists of Irinotecan (180 mg/m^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m^2 IV bolus, then 2400 mg/m^2 infused over 46 hours).

Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR).

The standard FOLFIRI regimen consists of Irinotecan (180 mg/m^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m^2 IV bolus, then 2400 mg/m^2 infused over 46 hours).

Period Title: Overall Study
Started 5 5
Completed [1] 0 2
Not Completed 5 3
Reason Not Completed
Adverse Event             0             1
Death             2             0
Progressive Disease             1             0
Withdrawal by Subject             2             1
Other Events             0             1
[1]
Two (2) patients were ongoing at the time of data cut-off for Primary Completion.
Arm/Group Title Dose Level 1: Sym004 12 mg/kg + FOLFIRI Dose Level -1: Sym004 9 mg/kg + FOLFIRI Total
Hide Arm/Group Description

Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR).

The standard FOLFIRI regimen consists of Irinotecan (180 mg/m^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m^2 IV bolus, then 2400 mg/m^2 infused over 46 hours).

Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR).

The standard FOLFIRI regimen consists of Irinotecan (180 mg/m^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m^2 IV bolus, then 2400 mg/m^2 infused over 46 hours).

Total of all reporting groups
Overall Number of Baseline Participants 5 5 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5 participants 5 participants 10 participants
69.3  (8.55) 61.1  (9.95) 65.2  (9.76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 5 participants 10 participants
Female
2
  40.0%
2
  40.0%
4
  40.0%
Male
3
  60.0%
3
  60.0%
6
  60.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 5 participants 10 participants
Hispanic or Latino
1
  20.0%
2
  40.0%
3
  30.0%
Not Hispanic or Latino
4
  80.0%
3
  60.0%
7
  70.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 5 participants 10 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
5
 100.0%
5
 100.0%
10
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 5 participants 10 participants
United States
3
  60.0%
2
  40.0%
5
  50.0%
Spain
2
  40.0%
3
  60.0%
5
  50.0%
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters (cm)
Number Analyzed 5 participants 5 participants 10 participants
170.4  (8.57) 171.3  (4.47) 170.9  (6.46)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms (kg)
Number Analyzed 5 participants 5 participants 10 participants
76.6  (11.97) 82.5  (16.10) 79.6  (13.73)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 5 participants 5 participants 10 participants
26.5  (4.20) 28.0  (4.52) 27.3  (4.19)
Body Surface Area (BSA)  
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 5 participants 5 participants 10 participants
1.9  (0.17) 2.0  (0.24) 1.9  (0.20)
1.Primary Outcome
Title Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03).
Hide Description AEs were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. The incidence and type of AEs (e.g., treatment-emergent AE [TEAE]) were summarized according to MedDRA system organ classes and preferred terms. An AE was considered as treatment-emergent if it occurred after the first treatment administration.
Time Frame 15 months
Hide Outcome Measure Data
Hide Analysis Population Description
All safety analyses were conducted using the Full Analysis Set (FAS) population, defined as all patients who received at least 1 dose of trial treatment.
Arm/Group Title Dose Level 1: Sym004 12 mg/kg + FOLFIRI Dose Level -1: Sym004 9 mg/kg + FOLFIRI
Hide Arm/Group Description:

Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR).

The standard FOLFIRI regimen consists of Irinotecan (180 mg/m^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m^2 IV bolus, then 2400 mg/m^2 infused over 46 hours).

Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR).

The standard FOLFIRI regimen consists of Irinotecan (180 mg/m^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m^2 IV bolus, then 2400 mg/m^2 infused over 46 hours).

Overall Number of Participants Analyzed 5 5
Measure Type: Count of Participants
Unit of Measure: Participants
At least 1 TEAE
5
 100.0%
5
 100.0%
At least 1 Serious TEAE
3
  60.0%
2
  40.0%
At least 1 Serious TEAE related to Sym004 only
0
   0.0%
0
   0.0%
At least 1 TEAE leading to Sym004 dose reduction
1
  20.0%
2
  40.0%
At least 1 TEAE leading to interruption of Sym004
3
  60.0%
5
 100.0%
At least 1 TEAE leading to Sym004 withdrawal
2
  40.0%
2
  40.0%
At least 1 TEAE leading to FOLFIRI withdrawal
1
  20.0%
2
  40.0%
At least 1 TEAE leading to trial termination
0
   0.0%
1
  20.0%
At least 1 TEAE related to Sym004 + FOLFIRI
4
  80.0%
3
  60.0%
At least 1 TEAE related to Sym004 only
4
  80.0%
5
 100.0%
At least 1 TEAE related to FOLFIRI only
4
  80.0%
4
  80.0%
At least 1 TEAE Grade ≥3 related to Sym004+FOLFIRI
2
  40.0%
2
  40.0%
At least 1 TEAE Grade ≥ 3 related to Sym004 only
0
   0.0%
2
  40.0%
At least 1 TEAE Grade ≥ 3 related to FOLFIRI only
1
  20.0%
1
  20.0%
At least 1 dermatologic toxicity
3
  60.0%
5
 100.0%
At least 1 TEAE of hypomagnesaemia
3
  60.0%
0
   0.0%
At least 1 Infusion related reaction TEAE
3
  60.0%
3
  60.0%
At least 1 TEAE resulting in death
0
   0.0%
0
   0.0%
Time Frame The adverse event data collection period was 15 months.
Adverse Event Reporting Description Adverse event data were collected beginning with the signing of informed consent and continued through 1 month (i.e., at least 28 days) after the last administration of treatment (i.e., after both Sym004 and FOLFIRI were discontinued). After the decision was made to prematurely discontinue the trial, collection of adverse event data continued through 1 month after the last administration of Sym004.
 
Arm/Group Title Dose Level 1: Sym004 12 mg/kg + FOLFIRI Dose Level -1: Sym004 9 mg/kg + FOLFIRI
Hide Arm/Group Description

Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR).

The standard FOLFIRI regimen consists of Irinotecan (180 mg/m^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m^2 IV bolus, then 2400 mg/m^2 infused over 46 hours).

Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR).

The standard FOLFIRI regimen consists of Irinotecan (180 mg/m^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m^2 IV bolus, then 2400 mg/m^2 infused over 46 hours).

All-Cause Mortality
Dose Level 1: Sym004 12 mg/kg + FOLFIRI Dose Level -1: Sym004 9 mg/kg + FOLFIRI
Affected / at Risk (%) Affected / at Risk (%)
Total   2/5 (40.00%)   0/5 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Dose Level 1: Sym004 12 mg/kg + FOLFIRI Dose Level -1: Sym004 9 mg/kg + FOLFIRI
Affected / at Risk (%) Affected / at Risk (%)
Total   3/5 (60.00%)   2/5 (40.00%) 
Gastrointestinal disorders     
Diarrhoea  1  2/5 (40.00%)  0/5 (0.00%) 
Intestinal obstruction  1  0/5 (0.00%)  1/5 (20.00%) 
Metabolism and nutrition disorders     
Hyponatraemia  1  1/5 (20.00%)  0/5 (0.00%) 
Nervous system disorders     
Syncope  1  0/5 (0.00%)  1/5 (20.00%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Dose Level 1: Sym004 12 mg/kg + FOLFIRI Dose Level -1: Sym004 9 mg/kg + FOLFIRI
Affected / at Risk (%) Affected / at Risk (%)
Total   5/5 (100.00%)   5/5 (100.00%) 
Blood and lymphatic system disorders     
Neutropenia  1  1/5 (20.00%)  4/5 (80.00%) 
Lymphopenia  1  1/5 (20.00%)  0/5 (0.00%) 
Eye disorders     
Cataract  1  0/5 (0.00%)  1/5 (20.00%) 
Gastrointestinal disorders     
Diarrhoea  1  3/5 (60.00%)  2/5 (40.00%) 
Stomatitis  1  3/5 (60.00%)  2/5 (40.00%) 
Vomiting  1  2/5 (40.00%)  3/5 (60.00%) 
Cheilitis  1  2/5 (40.00%)  1/5 (20.00%) 
Nausea  1  2/5 (40.00%)  1/5 (20.00%) 
Abdominal pain  1  1/5 (20.00%)  1/5 (20.00%) 
Abdominal pain upper  1  1/5 (20.00%)  0/5 (0.00%) 
Ascites  1  1/5 (20.00%)  0/5 (0.00%) 
Chapped lips  1  1/5 (20.00%)  0/5 (0.00%) 
Dry mouth  1  1/5 (20.00%)  0/5 (0.00%) 
Odynophagia  1  0/5 (0.00%)  1/5 (20.00%) 
Oral pain  1  1/5 (20.00%)  0/5 (0.00%) 
General disorders     
Fatigue  1  4/5 (80.00%)  2/5 (40.00%) 
Asthenia  1  1/5 (20.00%)  1/5 (20.00%) 
Non-cardiac chest pain  1  0/5 (0.00%)  2/5 (40.00%) 
Oedema peripheral  1  2/5 (40.00%)  0/5 (0.00%) 
Chest discomfort  1  0/5 (0.00%)  1/5 (20.00%) 
Chills  1  0/5 (0.00%)  1/5 (20.00%) 
Hepatobiliary disorders     
Hyperbilirubinaemia  1  1/5 (20.00%)  0/5 (0.00%) 
Infections and infestations     
Conjunctivitis  1  0/5 (0.00%)  1/5 (20.00%) 
Cystitis  1  0/5 (0.00%)  1/5 (20.00%) 
Hordeolum  1  0/5 (0.00%)  1/5 (20.00%) 
Influenza  1  0/5 (0.00%)  1/5 (20.00%) 
Paronychia  1  0/5 (0.00%)  1/5 (20.00%) 
Pneumonia  1  0/5 (0.00%)  1/5 (20.00%) 
Injury, poisoning and procedural complications     
Infusion related reaction  1  3/5 (60.00%)  3/5 (60.00%) 
Investigations     
Weight decreased  1  1/5 (20.00%)  1/5 (20.00%) 
Aspartate aminotransferase increased  1  1/5 (20.00%)  0/5 (0.00%) 
Blood bilirubin increased  1  1/5 (20.00%)  0/5 (0.00%) 
Lipase increased  1  1/5 (20.00%)  0/5 (0.00%) 
Weight increased  1  0/5 (0.00%)  1/5 (20.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  3/5 (60.00%)  0/5 (0.00%) 
Hypomagnesaemia  1  3/5 (60.00%)  0/5 (0.00%) 
Hyperglycaemia  1  1/5 (20.00%)  0/5 (0.00%) 
Hyperkalaemia  1  1/5 (20.00%)  0/5 (0.00%) 
Hypoalbuminaemia  1  1/5 (20.00%)  0/5 (0.00%) 
Hypokalaemia  1  0/5 (0.00%)  1/5 (20.00%) 
Hypophosphataemia  1  1/5 (20.00%)  0/5 (0.00%) 
Hypovolaemia  1  1/5 (20.00%)  0/5 (0.00%) 
Nervous system disorders     
Dysgeusia  1  1/5 (20.00%)  1/5 (20.00%) 
Syncope  1  1/5 (20.00%)  0/5 (0.00%) 
Amnesia  1  0/5 (0.00%)  1/5 (20.00%) 
Aphasia  1  0/5 (0.00%)  1/5 (20.00%) 
Dizziness  1  0/5 (0.00%)  1/5 (20.00%) 
Hypoaesthesia  1  0/5 (0.00%)  1/5 (20.00%) 
Paraesthesia  1  0/5 (0.00%)  1/5 (20.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  1/5 (20.00%)  2/5 (40.00%) 
Epistaxis  1  0/5 (0.00%)  2/5 (40.00%) 
Nasal inflammation  1  0/5 (0.00%)  1/5 (20.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis acneiform  1  2/5 (40.00%)  5/5 (100.00%) 
Dry skin  1  0/5 (0.00%)  2/5 (40.00%) 
Skin fissures  1  1/5 (20.00%)  1/5 (20.00%) 
Dermatitis allergic  1  0/5 (0.00%)  1/5 (20.00%) 
Dermatitis contact  1  0/5 (0.00%)  1/5 (20.00%) 
Rash maculo-papular  1  1/5 (20.00%)  0/5 (0.00%) 
Skin toxicity  1  0/5 (0.00%)  1/5 (20.00%) 
Vascular disorders     
Hypotension  1  1/5 (20.00%)  1/5 (20.00%) 
Capillary leak syndrome  1  1/5 (20.00%)  0/5 (0.00%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
The trial was terminated as development of Sym004 in combination with FOLFIRI was discontinued. The primary objective changed to assess the safety of the treatment combination; collection of data for secondary and exploratory objectives was omitted.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Publications shall not disclose any Sponsor confidential information and property (not including the trial results). The Sponsor reserves the right to review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The Sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Scientific Officer
Organization: Symphogen A/S
Phone: +45 8838 2600
EMail: info@symphogen.com
Layout table for additonal information
Responsible Party: Symphogen A/S
ClinicalTrials.gov Identifier: NCT02568046     History of Changes
Other Study ID Numbers: Sym004-09
2015-003047-19 ( EudraCT Number )
First Submitted: September 30, 2015
First Posted: October 5, 2015
Results First Submitted: December 19, 2018
Results First Posted: January 9, 2019
Last Update Posted: March 26, 2019