Trial Outcomes & Findings for Aflibercept +/- LV5FU2 in First Line of Non-resectalbe Metastatic Colorectal Cancers (NCT NCT02384759)

Last Updated: 2024-07-10

Results Overview

Progression was assessed by the investigator according to RECIST 1.1 criteria based on imaging studies performed every 8 weeks, even in case of deferred treatments. Clinical progressions, not confirmed on imaging, were not be counted in the primary endpoint

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

117 participants

Primary outcome timeframe

At 6 months after randomization

Results posted on

2024-07-10

Participant Flow

Between May 2015 and September 2020, 117 patients were randomized in France

Participant milestones

Participant milestones
Measure	Aflibercept + LV5FU2 LV5FU2: LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h. Aflibercept : Preceded or not by an IV infusion of aflibercept 4 mg/kg over 1 hour	LV5FU2 LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h.
Overall Study STARTED	59	58
Overall Study COMPLETED	56	56
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Aflibercept + LV5FU2 LV5FU2: LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h. Aflibercept : Preceded or not by an IV infusion of aflibercept 4 mg/kg over 1 hour	LV5FU2 LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h.
Overall Study Patients not treated	3	2

Baseline Characteristics

Aflibercept +/- LV5FU2 in First Line of Non-resectalbe Metastatic Colorectal Cancers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aflibercept + LV5FU2 n=56 Participants LV5FU2: LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h. Aflibercept : Preceded or not by an IV infusion of aflibercept 4 mg/kg over 1 hour	LV5FU2 n=56 Participants LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h.	Total n=112 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	56 Participants n=5 Participants	56 Participants n=7 Participants	112 Participants n=5 Participants
Age, Continuous	80.27 years STANDARD_DEVIATION 5.43 • n=5 Participants	80.23 years STANDARD_DEVIATION 5.40 • n=7 Participants	80.25 years STANDARD_DEVIATION 5.39 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	23 Participants n=7 Participants	44 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	33 Participants n=7 Participants	68 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	56 Participants n=5 Participants	56 Participants n=7 Participants	112 Participants n=5 Participants
Region of Enrollment France	56 participants n=5 Participants	56 participants n=7 Participants	112 participants n=5 Participants

PRIMARY outcome

Timeframe: At 6 months after randomization

Population: Analysis population is the mITT population defined as all the patients randomized having received at least one dose of study treatment

Outcome measures

Outcome measures
Measure	Aflibercept + LV5FU2 n=56 Participants LV5FU2: LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h. Aflibercept : Preceded or not by an IV infusion of aflibercept 4 mg/kg over 1 hour	LV5FU2 n=56 Participants LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h.
The Primary Objective Was the Percentage of Patients Alive and Without Progression 6 Months After the Randomization. Percentage of patients alive without progression at 6 months	30 Participants	30 Participants
The Primary Objective Was the Percentage of Patients Alive and Without Progression 6 Months After the Randomization. Percentage of patients with progression or death at 6 months	26 Participants	26 Participants

SECONDARY outcome

Timeframe: Up to 3 years after the treatment start

Overall survival was defined as the time from the date of randomization to the patient's death (all causes). For alive patients, the date of the latest news was taken into account

Outcome measures

Outcome measures
Measure	Aflibercept + LV5FU2 n=56 Participants LV5FU2: LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h. Aflibercept : Preceded or not by an IV infusion of aflibercept 4 mg/kg over 1 hour	LV5FU2 n=56 Participants LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h.
Overall Survival (OS)	21.85 months Interval 12.09 to 25.03	25.07 months Interval 19.84 to 31.93

SECONDARY outcome

Timeframe: up to 12 months after randomization

It was defined as the time between t randomization and the date of the first radiological progression (RECIST 1.1 criteria) according to the investigator or death; Patients alive without progression were censored at the date of last news

Outcome measures

Outcome measures
Measure	Aflibercept + LV5FU2 n=56 Participants LV5FU2: LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h. Aflibercept : Preceded or not by an IV infusion of aflibercept 4 mg/kg over 1 hour	LV5FU2 n=56 Participants LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h.
Progression-free Survival (PPFS)	7.28 months Interval 5.59 to 8.25	7.23 months Interval 5.59 to 9.63

Adverse Events

Aflibercept + LV5FU2

Serious events: 26 serious events

Other events: 55 other events

Deaths: 37 deaths

LV5FU2

Serious events: 13 serious events

Other events: 56 other events

Deaths: 36 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Aflibercept + LV5FU2 n=56 participants at risk LV5FU2: LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h. Aflibercept : Preceded or not by an IV infusion of aflibercept 4 mg/kg over 1 hour	LV5FU2 n=56 participants at risk LV5FU2: LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h.
Blood and lymphatic system disorders Anemia	66.1% 37/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	75.0% 42/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Musculoskeletal and connective tissue disorders Dorsalgia	7.1% 4/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	12.5% 7/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Respiratory, thoracic and mediastinal disorders Voice alteration	19.6% 11/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	1.8% 1/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Respiratory, thoracic and mediastinal disorders Epitaxis	25.0% 14/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	16.1% 9/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Vascular disorders Hypertension	66.1% 37/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	35.7% 20/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Metabolism and nutrition disorders Anorexia	55.4% 31/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	30.4% 17/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
General disorders Fatigue	87.5% 49/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	76.8% 43/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)

Additional Information

Karine Le Malicot

Fédération Francophone de Cancérologie Digestive

Phone: +33 3 80 39 34 79

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Aflibercept + LV5FU2 n=56 participants at risk LV5FU2: LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h. Aflibercept : Preceded or not by an IV infusion of aflibercept 4 mg/kg over 1 hour	LV5FU2 n=56 participants at risk LV5FU2: LV5FU2 simplified every 2 weeks: folinic acid 400 mg/m2 IV over 90 min, then 5FU 400 mg/m2 IV bolus at D1, followed by continuous infusion of 5FU 2400 mg/m2 over 46 h.
Cardiac disorders Thoracic Pain	0.00% 0/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	1.8% 1/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Cardiac disorders Auricular Fibrillation	1.8% 1/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	0.00% 0/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Cardiac disorders Cardiac insufficiency	0.00% 0/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	1.8% 1/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Nervous system disorders AVC	3.6% 2/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	0.00% 0/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Nervous system disorders Cephalgia	3.6% 2/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	0.00% 0/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Gastrointestinal disorders Diarrhea	5.4% 3/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	0.00% 0/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Gastrointestinal disorders Vomiting	3.6% 2/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	1.8% 1/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Psychiatric disorders Mental confusion	3.6% 2/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	1.8% 1/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Vascular disorders Veinous thromboembolic event	3.6% 2/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	1.8% 1/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Vascular disorders Hypertension	3.6% 2/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	0.00% 0/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Blood and lymphatic system disorders Haemorrhage	7.1% 4/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	0.00% 0/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Metabolism and nutrition disorders Anorexia	3.6% 2/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	1.8% 1/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
General disorders Fatigue	10.7% 6/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	0.00% 0/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
General disorders Fever	5.4% 3/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	1.8% 1/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Injury, poisoning and procedural complications Burning	0.00% 0/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	1.8% 1/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Nervous system disorders Dysphasia	0.00% 0/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	1.8% 1/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Nervous system disorders Cerebrovascular Ischemia	0.00% 0/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	3.6% 2/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Gastrointestinal disorders Abdominal pain	0.00% 0/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	1.8% 1/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)
Gastrointestinal disorders Small bowel obstruction	0.00% 0/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)	1.8% 1/56 • Up to the end of treatment, on the average of 18 months. Death were monitored even the patient has stopped the study treatment (up to 3 years) whereas adverse events were monitored until the end of the study protocol (average of treatment=18 months)