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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01670721




Registration number
NCT01670721
Ethics application status
Date submitted
13/07/2012
Date registered
22/08/2012
Date last updated
28/11/2016

Titles & IDs
Public title
Colorectal Cancer Metastatic
Scientific title
A Multicenter, Single Arm, Open Label Clinical Trial Evaluating Safety and Health Related Quality of Life of Aflibercept in Combination With Irinotecan/5-FU Chemotherapy (FOLFIRI) in Patients With Metastatic Colorectal Cancer (mCRC) Previously Treated With an Oxaliplatin-Containing Regimen
Secondary ID [1] 0 0
2012-000048-89
Secondary ID [2] 0 0
AFLIBL06266
Universal Trial Number (UTN)
Trial acronym
AFEQT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer Metastatic 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AFLIBERCEPT
Treatment: Drugs - Irinotecan
Treatment: Drugs - Fluorouracil
Treatment: Drugs - Leucovorin

Experimental: Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin) - Aflibercept 4 mg/kg intravenous (IV) infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.


Treatment: Drugs: AFLIBERCEPT
Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous

Treatment: Drugs: Irinotecan
Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous

Treatment: Drugs: Fluorouracil
Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous

Treatment: Drugs: Leucovorin
Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Adverse Events (AEs)
Timepoint [1] 0 0
Baseline upto 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure:723 days)
Secondary outcome [1] 0 0
Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment for Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Timepoint [1] 0 0
Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)
Secondary outcome [2] 0 0
Change From Baseline in HRQL European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Score
Timepoint [2] 0 0
Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)
Secondary outcome [3] 0 0
Change From Baseline in HRQL EQ-5D-3L VAS Score
Timepoint [3] 0 0
Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)

Eligibility
Key inclusion criteria
Inclusion criteria:

- Histologically or cytologically proven adenocarcinoma of the colon or rectum.

- Metastatic disease.

- Age =18 years.

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

- One and only one prior chemotherapeutic regimen for metastatic disease. This prior
chemotherapy must be an oxaliplatin containing regimen. Participants must progressed
during or following the last administration of the oxaliplatin based chemotherapy.
Participants relapsing within 6 months of completion of oxaliplatin adjuvant
chemotherapy were also eligible.

- Participants must be affiliated to a Social Security System.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

Related to Methodology

- Prior therapy with irinotecan; Absolute neutrophil counts (ANC) <1.5 x 109/L; Platelet
count <100 x 109/L; Hemoglobin <9.0 g/dL; Total bilirubin >1.5 x upper limit of normal
(ULN); Transaminases >3 x ULN (unless liver metastasis are present, 5 x ULN in that
case); Alkaline phosphatase >3 x ULN (unless liver metastasis are present, 5 x ULN in
that case).

- Less than 4 weeks elapsed from prior radiotherapy or prior chemotherapy or major
surgery to the time of inclusion or until the surgical wound was fully healed
whichever came later (48 hours in case of minor surgical procedure or until wound full
healing observed).

- Treatment with any investigational drug within 30 days prior to inclusion.

- AEs (with exception of alopecia, peripheral sensory neuropathy and those listed in
specific exclusion criteria) from any prior anti cancer therapy of grade >1 National
Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v.4.0 at
the time of inclusion.

- History of brain metastases, uncontrolled spinal cord compression, or carcinomatous
meningitis or new evidence of brain or leptomeningeal disease.

- Other prior malignancy. Basal cell or squamous cell skin cancer, carcinoma in situ of
the cervix or any other cancer from which the participant had been disease free for >5
years were allowed.

- Any of the following within 6 months prior to inclusion: myocardial infarction,
severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York
Heart Association (NYHA) class III or IV congestive heart failure, stroke or transient
ischemic attack.

- Any of the following within 3 months prior to inclusion: Grade 3-4 gastrointestinal
bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis or
gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary
embolism or other uncontrolled thromboembolic event.

- Occurrence of deep vein thrombosis within 4 weeks, prior to inclusion.

- Known acquired immunodeficiency syndrome (AIDS)-related illnesses or known human
deficiency virus (HIV) disease requiring antiretroviral treatment.

- Any severe acute or chronic medical condition, which could impair the ability of the
participant to participate to the study or to interfere with interpretation of study
results.

- Pregnant or breast-feeding women. Positive pregnancy test for women of reproductive
potential.

- Participants with reproductive potential (female and male) who did not agree to use a
method of contraception during the study treatment period and for at least 6 months
following completion of study treatment. The definition of effective method was left
to the investigator's judgment.

Related to Aflibercept:

- Urine protein-creatinine ratio (UPCR) >1 on morning spot urinalysis or proteinuria >
500 mg/24-h.

- Serum creatinine >1.5 x ULN . If creatinine 1.0-1.5 x ULN, creatinine clearance,
calculated according to Cockroft-Gault formula, <60 ml/min will exclude the
participant.

- Uncontrolled hypertension (blood pressure >140/90 mmHg or systolic blood pressure >160
mmHg when diastolic blood pressure <90 mmHg, on at least 2 repeated determinations on
separate days, or upon clinical judgement within 3 months prior to study inclusion.

- Participants on anticoagulant therapy with unstable dose of warfarin and/or having an
out-of-therapeutic range international normalized ratio (INR) (>3) within the 4 weeks
prior to inclusion.

- Evidence of clinically significant bleeding diathesis or underlying coagulopathy (e.g.
INR >1.5 without vitamine K antagonist therapy), non-healing wound.

Related to FOLFIRI

- Known dihydropyrimidine dehydrogenase deficiency.

- Predisposing colonic or small bowel disorders in which the symptoms were uncontrolled
as indicated by baseline of >3 loose stools daily.

- Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea,
unresolved bowel obstruction/sub-obstruction, more than hemicolectomy, extensive small
intestine resection with chronic diarrhea.

- History of anaphylaxis or known intolerance to atropine sulphate or loperamide or
appropriate antiemetics to be administered in conjunction with FOLFIRI.

- Treatment with concomitant anticonvulsivant agents that are cytochrome P450 3A4
(CYP3A4) inducers (phenytoin, phenobarbital, carbamazepine), unless discontinued >7
days.

- Participants with known Gilbert's syndrome.

The above information was not intended to contain all considerations relevant to a
participant's potential participation in a clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2015
Sample size
Target
Accrual to date
Final
175
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
France
State/province [1] 0 0
Paris

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Regeneron Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objective:

To evaluate the safety of aflibercept in participants with mCRC treated with
irinotecan/5-Fluorouracil (5-FU) combination (FOLFIRI) after failure of an oxaliplatin-based
regimen (participants similar to those evaluated in the VELOUR trial [EFC10262, NCT00561470])
according to side effects prevention and management guidelines.

Secondary Objective:

To document the Health-Related Quality of Life (HRQL) of aflibercept in this participant
population.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01670721
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries