Colorectal Cancer MetastaticPhase 3AFEQTNCT01670721
Colorectal Cancer Metastatic
A Phase 3 study testing AFLIBERCEPT, Irinotecan and Fluorouracil in people with Colorectal Cancer Metastatic, run by Sanofi at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer Metastatic
- What is being tested?
- AFLIBERCEPT, Irinotecan and Fluorouracil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 175 participants
- Where
- 1 siteFrance
- Study dates
- Aug 2012to Jun 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official 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
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.
Read the detailed description
Each participant was treated until disease progression (DP), unacceptable toxicity, death, Investigator's decision or participant's refusal for further treatment (whichever come first). Participants were followed-up during treatment and for at least 30 days after its last study treatment (either Aflibercept or FOLFIRI) administration, up to a maximum of 6 months.
- Conditions
- Colorectal Cancer Metastatic
- Being tested
- AFLIBERCEPT, Irinotecan, Fluorouracil, Leucovorin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AFLIBERCEPTDrug
Also called AVE0005
Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous
IrinotecanDrug
Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous
FluorouracilDrug
Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous
LeucovorinDrug
Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous
| Study group | Role | What they receive |
|---|---|---|
| Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin) | Experimental | 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. Receives: Drug: AFLIBERCEPT; Drug: Irinotecan; Drug: Fluorouracil; Drug: Leucovorin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Adverse Events (AEs)
Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period. On-treatment period was defined as the time from the first dose of treatment to 30 days after the last dose of treatment (either Aflibercept or FOLFIRI). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.
Measured: Baseline upto 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure:723 days)
Secondary outcomes (3)
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)
EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) \& other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health \& quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 \& 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant.
Measured: 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)
Change From Baseline in HRQL European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Score
EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). EQ-5D descriptive system comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression measured on 3 levels (no problem, some problems \& severe problems) within a particular EQ-5D dimension. 5 dimensional 3-level system was converted into single index utility score. Possible values for single index utility score ranged from -0.594 (severe problems in all dimensions) to 1.0 (no problem in all dimensions) on scale where 1 represented best possible health state.
Measured: 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)
Change From Baseline in HRQL EQ-5D-3L VAS Score
EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state. Baseline corresponded to last evaluable assessment before treatment administration.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2012 (estimated)
- Study startAug 2012
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colorectal Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 175 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01670721
- Sponsor's protocol ID
- AFLIBL06266
- Other IDs
- 2012-000048-89, U1111-1128-9325
- Acronym
- AFEQT
- Status last verified
- Oct 2016
- First submitted
- 13 Jul 2012
- Last updated
- 28 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01670721
- Acronym / sponsor ID
- AFEQT / AFLIBL06266
- Conditions
- Colorectal Cancer Metastatic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 175 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- Aug 2012
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 22 Aug 2012 (estimated)
- Results
- Posted 28 Nov 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Each participant was treated until disease progression (DP), unacceptable toxicity, death, Investigator's decision or participant's refusal for further treatment (whichever come first). Participants were followed-up during treatment and for at least 30 days after its last study treatment (either Aflibercept or FOLFIRI) administration, up to a maximum of 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin) | Experimental | Drug: AFLIBERCEPT, Drug: Irinotecan, Drug: Fluorouracil, Drug: LeucovorinAflibercept 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (28 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AFLIBERCEPTAlso: AVE0005Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous | Drug | Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin) |
| IrinotecanPharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous | Drug | Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin) |
| FluorouracilPharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous | Drug | Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin) |
| LeucovorinPharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous | Drug | Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin) |
Primary outcome
Percentage of Participants With Adverse Events (AEs)
Time frame: Baseline upto 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure:723 days)
Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period. On-treatment period was defined as the time from the first dose of treatment to 30 days after the last dose of treatment (either Aflibercept or FOLFIRI). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.
3 secondary outcomes
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)
Time frame: 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)
Change From Baseline in HRQL European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Score
Time frame: 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)
Change From Baseline in HRQL EQ-5D-3L VAS Score
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AFLIBERCEPT, Irinotecan and Fluorouracil in people with Colorectal Cancer Metastatic, run by Sanofi at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Adverse Events (AEs) (time frame: Baseline upto 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure:723 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2016.