Trial Outcomes & Findings for Sym004 in SCCHN Patients Failing Anti-EGFR Based Therapy (NCT NCT01417936)
NCT ID: NCT01417936
Last Updated: 2018-10-15
Results Overview
The PFS time was defined as the time from first infusion of Sym004 until progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. or death. PD was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The unequivocal progression of existing non-target lesions and the appearance of one or more lesions was also considered progression. Subjects who died without confirmed PD were considered as progressed. Subjects who died or showed PD more than 21 days after last treatment were censored (that is, were considered alive without progression on Day 21 after last treatment). Evaluation was done using Kaplan-Meier estimates.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
26 participants
Primary outcome timeframe
Time from the first infusion of Sym004 until progressive disease or death, assessed up to 24 weeks
Results posted on
2018-10-15
Participant Flow
First subject (informed consent): 15 July 2011. Last subject completed: 08 October 2012; Clinical data cut-off: 08 October 2012. Subjects randomized at 10 centers in Belgium, France and Germany.
A total of 28 subjects were screened for eligibility, 2 were excluded (mainly non-fulfillment of inclusion or exclusion criteria) and 26 subjects were randomized.
Participant milestones
| Measure |
Sym004
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Overall Study
STARTED
|
26
|
|
Overall Study
COMPLETED
|
26
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Sym004 in SCCHN Patients Failing Anti-EGFR Based Therapy
Baseline characteristics by cohort
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Age, Continuous
|
62.0 years
STANDARD_DEVIATION 10.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Time from the first infusion of Sym004 until progressive disease or death, assessed up to 24 weeksPopulation: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment.
The PFS time was defined as the time from first infusion of Sym004 until progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. or death. PD was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The unequivocal progression of existing non-target lesions and the appearance of one or more lesions was also considered progression. Subjects who died without confirmed PD were considered as progressed. Subjects who died or showed PD more than 21 days after last treatment were censored (that is, were considered alive without progression on Day 21 after last treatment). Evaluation was done using Kaplan-Meier estimates.
Outcome measures
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Progression Free Survival (PFS) Time
|
82 days
Interval 41.0 to 140.0
|
SECONDARY outcome
Timeframe: Time from first infusion of Sym004 until disease progression or death, assessed up to 18 monthsPopulation: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment.
Best objective tumor response was defined as the occurrence of complete response (CR), partial response (PR), stable disease (SD), or PD according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Objective response was defined as the occurrence of CR or PR according to RECIST Version 1.1. Disease control was defined as the occurrence of CR, PR or SD according to RECIST Version 1.1. CR: Disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 mm; PR: At least a 30% decrease in the sum of diameters of all - lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on trial.
Outcome measures
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Objective Tumor Response and Derived Endpoints (Objective Response Rate and Disease Control Rate)
CR
|
0 Percentage of subjects
Interval 0.0 to 0.0
|
|
Objective Tumor Response and Derived Endpoints (Objective Response Rate and Disease Control Rate)
PR
|
0 Percentage of subjects
Interval 0.0 to 0.0
|
|
Objective Tumor Response and Derived Endpoints (Objective Response Rate and Disease Control Rate)
SD
|
50.0 Percentage of subjects
Interval 29.9 to 70.1
|
|
Objective Tumor Response and Derived Endpoints (Objective Response Rate and Disease Control Rate)
PD
|
23.1 Percentage of subjects
Interval 9.0 to 43.6
|
SECONDARY outcome
Timeframe: Time from first infusion of Sym004 until disease progression or death, assessed up to 18 monthsPopulation: Duration of overall response could not be calculated as no subject showed CR or PR.
Duration of overall response was defined as the time from the first time point where measurement criteria are met for CR or PR until first date of recurrence or PD was objectively documented according to RECIST Version 1.1. Duration of overall response was censored at date of last imaging data of measured lesions if no confirmation of recurrence or PD was available.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time from first infusion of Sym04 until disease progression, assessed up to 18 monthsPopulation: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment.
The TTP was defined as the time from first infusion of Sym004 until disease progression according to RECIST Version 1.1 criteria. Disease progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The subjects who died without prior assessment of PD were censored for TTP.
Outcome measures
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Time to Progression (TTP)
|
85 days
Interval 42.0 to 147.0
|
SECONDARY outcome
Timeframe: Time from first infusion of Sym004 until death, assessed up to 18 monthsPopulation: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment.
Overall survival time was defined as the time from first infusion of Sym004 until date of death. Subjects who withdraw the consent or lost to follow-up were censored.
Outcome measures
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Overall Survival Time
|
156 days
Interval 86.0 to 202.0
|
SECONDARY outcome
Timeframe: Weeks 0 and 4; and 4 weeks after last dosePopulation: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. "n" signifies subjects evaluable for specified biomarker type.
The biomarkers human papilloma virus (HPV), mutated epidermal growth factor receptor (EGFRvIII), c-MET and human epidermal growth factor receptor (HER) 2, HER3 were analyzed only in tumor cells while EGFR, phosphorylated epidermal growth factor receptor (pEGFR), and Ki-67 were analyzed both in tumor and skin biopsy cells.
Outcome measures
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Number of Subjects With Detectable Biomarkers at Any Visit
Tumor biopsy: HPV (n=19)
|
1 Subjects
|
|
Number of Subjects With Detectable Biomarkers at Any Visit
Tumor biopsy: EGFRvIII (n=21)
|
0 Subjects
|
|
Number of Subjects With Detectable Biomarkers at Any Visit
Tumor biopsy: cMET (n=19)
|
6 Subjects
|
|
Number of Subjects With Detectable Biomarkers at Any Visit
Tumor biopsy: HER2 (n=17)
|
0 Subjects
|
|
Number of Subjects With Detectable Biomarkers at Any Visit
Tumor biopsy: HER3 (n=17)
|
0 Subjects
|
|
Number of Subjects With Detectable Biomarkers at Any Visit
Skin biopsy: EGFR (n=18)
|
0 Subjects
|
|
Number of Subjects With Detectable Biomarkers at Any Visit
Tumor biopsy: EGFR (n=11)
|
0 Subjects
|
|
Number of Subjects With Detectable Biomarkers at Any Visit
Tumor biopsy: pEGFR (n=26)
|
0 Subjects
|
|
Number of Subjects With Detectable Biomarkers at Any Visit
Skin biopsy: pEGFR (n=26)
|
0 Subjects
|
|
Number of Subjects With Detectable Biomarkers at Any Visit
Skin biopsy: Increase in Ki67 (n=18)
|
9 Subjects
|
|
Number of Subjects With Detectable Biomarkers at Any Visit
Skin biopsy: Decrease in Ki67 (n=18)
|
9 Subjects
|
|
Number of Subjects With Detectable Biomarkers at Any Visit
Tumor biopsy: Decrease in Ki67 (n=11)
|
4 Subjects
|
SECONDARY outcome
Timeframe: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
The AUC (0-168h) was estimated by determining the total area under the curve of the concentration versus time curve.
Outcome measures
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Area Under the Serum Concentration Curve From Time Zero to 168 Hours (AUC [0-168])
Week 0 (n=26)
|
17574.9 microgram-hour/milliliter
Standard Deviation 5863.6
|
|
Area Under the Serum Concentration Curve From Time Zero to 168 Hours (AUC [0-168])
Week 3 (n=23)
|
25690.8 microgram-hour/milliliter
Standard Deviation 14857.1
|
SECONDARY outcome
Timeframe: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
The AUC (0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Outcome measures
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Area Under the Serum Concentration Curve From Time Zero to Infinity (AUC [0-inf])
Week 0 (n=24)
|
24620.8 microgram-hour/milliliter
Standard Deviation 7883.7
|
|
Area Under the Serum Concentration Curve From Time Zero to Infinity (AUC [0-inf])
Week 3 (n=15)
|
61655.7 microgram-hour/milliliter
Standard Deviation 22954.9
|
SECONDARY outcome
Timeframe: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
Outcome measures
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Maximum Serum Concentration (Cmax)
Week 0 (n=26)
|
248.4 microgram/milliliter
Standard Deviation 82.7
|
|
Maximum Serum Concentration (Cmax)
Week 3 (n=23)
|
299.8 microgram/milliliter
Standard Deviation 139.0
|
SECONDARY outcome
Timeframe: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
Outcome measures
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Minimum Serum Concentration (Cmin)
Week 0 (n=26)
|
48.2 microgram/milliliter
Standard Deviation 20.1
|
|
Minimum Serum Concentration (Cmin)
Week 3 (n=23)
|
93.6 microgram/milliliter
Standard Deviation 45.3
|
SECONDARY outcome
Timeframe: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.
Outcome measures
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Clearance (CL)
Week 0 (n=24)
|
0.55 milliliter/hour/kilogram
Standard Deviation 0.22
|
|
Clearance (CL)
Week 3 (n=15)
|
0.22 milliliter/hour/kilogram
Standard Deviation 0.08
|
SECONDARY outcome
Timeframe: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
The apparent terminal half-life was defined as the time required for the serum concentration of Sym004 to decrease 50% in the final stage of its elimination.
Outcome measures
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Terminal Half Life (T1/2)
Week 0 (n=24)
|
89.1 hour
Standard Deviation 26.5
|
|
Terminal Half Life (T1/2)
Week 3 (n=15)
|
140.7 hour
Standard Deviation 37.6
|
SECONDARY outcome
Timeframe: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
Outcome measures
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Time to Reach Maximum Serum Concentration (Tmax)
Week 0 (n=26)
|
6.0 hour
Standard Deviation 5.4
|
|
Time to Reach Maximum Serum Concentration (Tmax)
Week 3 (n=23)
|
4.7 hour
Standard Deviation 3.4
|
SECONDARY outcome
Timeframe: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
Outcome measures
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Time to Reach Minimum Serum Concentration (Tmin)
Week 0 (n=26)
|
163.5 hour
Standard Deviation 22.9
|
|
Time to Reach Minimum Serum Concentration (Tmin)
Week 3 (n=23)
|
58.4 hour
Standard Deviation 81.8
|
SECONDARY outcome
Timeframe: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
Volume of distribution was defined as the theoretical volume in which the total amount of drug needed to be uniformly distributed to produce the desired serum concentration of a drug.
Outcome measures
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Volume of Distribution (Vz)
Week 0 (n=24)
|
67.0 milliliter/kilogram
Standard Deviation 23.2
|
|
Volume of Distribution (Vz)
Week 3 (n=15)
|
40.9 milliliter/kilogram
Standard Deviation 10.3
|
SECONDARY outcome
Timeframe: From the first dose of study drug administration up to 4 weeks after the last dose of study drug administrationPopulation: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment.
An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Outcome measures
| Measure |
Sym004
n=26 Participants
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Number of Subjects With Adverse Events (AEs), Serious AEs, AEs Leading to Death and AEs Leading to Discontinuation
AEs
|
26 Subjects
|
|
Number of Subjects With Adverse Events (AEs), Serious AEs, AEs Leading to Death and AEs Leading to Discontinuation
SAEs
|
20 Subjects
|
|
Number of Subjects With Adverse Events (AEs), Serious AEs, AEs Leading to Death and AEs Leading to Discontinuation
AEs Leading to Death
|
5 Subjects
|
|
Number of Subjects With Adverse Events (AEs), Serious AEs, AEs Leading to Death and AEs Leading to Discontinuation
AEs Leading to Discontinuation
|
6 Subjects
|
Adverse Events
Sym004
Serious events: 20 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sym004
n=26 participants at risk
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Gastrointestinal disorders
Abdominal pain upper
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Gastrointestinal disorders
Dysphagia
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Gastrointestinal disorders
Jejunal perforation
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Asthenia
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Death
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
General physical health deterioration
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Device related infection
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Herpes zoster ophthalmic
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Pneumonia
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Sepsis
|
11.5%
3/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Urinary tract infection bacterial
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
15.4%
4/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Musculoskeletal and connective tissue disorders
Fistula
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant
|
23.1%
6/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor haemorrhage
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Stridor
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Surgical and medical procedures
Prosthesis implantation
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Surgical and medical procedures
Surgery
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
Other adverse events
| Measure |
Sym004
n=26 participants at risk
Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
|
|---|---|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
61.5%
16/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
50.0%
13/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
46.2%
12/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Skin and subcutaneous tissue disorders
Erythema
|
42.3%
11/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Skin and subcutaneous tissue disorders
Rash
|
30.8%
8/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Skin and subcutaneous tissue disorders
Skin fissures
|
23.1%
6/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
15.4%
4/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
15.4%
4/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Skin and subcutaneous tissue disorders
Eczema
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Skin and subcutaneous tissue disorders
Nail dystrophy
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Fatigue
|
38.5%
10/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Gastrointestinal disorders
Oedema peripheral
|
23.1%
6/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Face oedema
|
15.4%
4/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Asthenia
|
11.5%
3/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
General physical health deterioration
|
11.5%
3/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Mucosal inflammation
|
11.5%
3/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Chills
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Influenza like illness
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Pain
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Catheter site erythema
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Chest pain
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Device leakage
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Device occlusion
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Local swelling
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Pyrexia
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
General disorders
Xerosis
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Gastrointestinal disorders
Diarrhoea
|
34.6%
9/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Gastrointestinal disorders
Nausea
|
30.8%
8/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Gastrointestinal disorders
Stomatitis
|
23.1%
6/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Gastrointestinal disorders
Vomiting
|
19.2%
5/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Gastrointestinal disorders
Constipation
|
11.5%
3/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Gastrointestinal disorders
Dysphagia
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Gastrointestinal disorders
Aphthous stomatitis'
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Gastrointestinal disorders
Ascites
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Gastrointestinal disorders
Lip oedema
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Gastrointestinal disorders
Lip ulceration
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Folliculitis
|
19.2%
5/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Infection
|
11.5%
3/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Paronychia
|
11.5%
3/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Impetigo
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Rhinitis
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Wound infection
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Abscess jaw
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Candidiasis
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Catheter site infection
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Dermatitis infected
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Eye infection
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Gastroenteritis
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Nail infection
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Purulence
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Sputum purulent
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Tinea pedis
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
50.0%
13/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
50.0%
13/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Infections and infestations
Hypoalbuminaemia
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Metabolism and nutrition disorders
Dehydration
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
11.5%
3/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
11.5%
3/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Nasal discomfort
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal oedema
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Respiratory, thoracic and mediastinal disorders
Tracheal fistula
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Blood and lymphatic system disorders
Anaemia
|
26.9%
7/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Blood and lymphatic system disorders
Coagulopathy
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Nervous system disorders
Dizziness
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Nervous system disorders
Neuropathy peripheral
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Nervous system disorders
Paraesthesia
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Nervous system disorders
Tremor
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Vascular disorders
Hypotension
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Vascular disorders
Flushing
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Vascular disorders
Haematoma
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Vascular disorders
Hyperaemia
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Vascular disorders
Hypertension
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Vascular disorders
Peripheral coldness
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Vascular disorders
Thrombosis
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Injury, poisoning and procedural complications
Jaw fracture
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Injury, poisoning and procedural complications
Procedural pain
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Injury, poisoning and procedural complications
Wound
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
11.5%
3/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour ulceration
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour necrosis
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Eye disorders
Conjunctivitis
|
11.5%
3/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Eye disorders
Dry eye
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Eye disorders
Eyelid oedema
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Psychiatric disorders
Aggression
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Psychiatric disorders
Anxiety
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Psychiatric disorders
Confusional state
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Psychiatric disorders
Insomnia
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Investigations
Weight decreased
|
7.7%
2/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Investigations
Blood creatinine increased
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Investigations
C-reactive protein increased
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Investigations
Neutrophil count increased
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Investigations
Staphylococcus test positive
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Investigations
White blood cell count increased
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Renal and urinary disorders
Haematuria
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Renal and urinary disorders
Renal failure
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Renal and urinary disorders
Renal failure chronic
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Renal and urinary disorders
Urinary tract obstruction
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Cardiac disorders
Atrial fibrillation
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Ear and labyrinth disorders
Otorrhoea
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Endocrine disorders
Hyperglycaemia
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
|
Musculoskeletal and connective tissue disorders
Fistula
|
3.8%
1/26 • From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER