Safety and Quality of Life Study of Aflibercept in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin-Based Regimen
- Conditions
- Colorectal Cancer Metastatic
- Interventions
- Drug: FOLFIRI
- Registration Number
- NCT01571284
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To provide metastatic colorectal cancer participants with access to aflibercept and to document the overall safety in these participants
Secondary Objective:
To document the Health-Related Quality of Life of aflibercept in this participants population
- Detailed Description
Each participants will be treated until disease progression, unacceptable toxicity, death, Investigator's decision or participant's refusal for further treatment (whichever comes first). Participants were followed-up during study treatment and for at least 30 days after last administration.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 781
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin) AFLIBERCEPT AVE0005 Aflibercept 4 mg/kg 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-Fluorouracil (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 disease progression (DP), unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment. Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin) FOLFIRI Aflibercept 4 mg/kg 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-Fluorouracil (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 disease progression (DP), unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
- Primary Outcome Measures
Name Time Method Number of Participants With Abnormal Renal and Liver Function Parameters Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks) Renal and liver function parameters included: creatinine, hyperbilirubinemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase. Number of participants with each of these parameters were analyzed by grades (All Grades and Grades 3-4) as per NCI CTCAE version 4.03, where Grade 1=mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling. All Grades included Grades 1-4.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks) Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an adverse event (AE) without regard to possibility of causal relationship with this treatment. A serious AE (SAE): 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. National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Version 4.03 was used to assess severity (Grade 1=mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling) of AEs.
Number of Participants With Abnormal Hematological Parameters Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks) Abnormal hematological parameters included: anaemia, thrombocytopenia, leukopenia and neutropenia. Number of participants with each of these parameters were analyzed by grades (All Grades and Grades 3-4 as per NCI CTCAE (Version 4.03), where Grade 1=mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling. All Grades included Grades 1-4.
Number of Participants With International Normalized Ratio (INR) Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks) The INR is a derived measure of the prothrombin time. The INR is the ratio of a participant's prothrombin time to a normal control sample. Normal range (without anti coagulation therapy): 0.8-1.2; Targeted range (with anti coagulation therapy) 2.0-3.0.
Number of Participants With Abnormal Electrolytes Parameters Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks) Abnormal electrolytes parameters included: hyponatremia, hypernatremia, hypocalcemia, hypercalcemia, hypokalemia, and hyperkalemia. Number of participants with each of these parameters were analyzed by grades ( All Grades and Grades 3-4 as per NCI CTCAE Version 4.03, where Grade 1=mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling. All Grades included Grades 1-4.
Creatinine Clearance of Aflibercept Plus FOLFIRI Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks) Creatinine clearance is a measure of kidney function. Creatinine clearance rate is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Creatinine clearance can be measured directly or estimated using established formulas. For this study, the creatinine clearance was calculated using the Cockroft-Gault or Modification of Diet in Renal Disease (MDRD).
Number of Participants With Other Abnormal Biochemistry Parameters Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks) Other abnormal biochemistry parameters included: hypoglycemia, hyperglycemia and hypoalbuminemia. Number of participants with each of these parameters were analyzed by grades (All Grades and Grades 3-4) as per NCI CTCAE Version 4.03, where Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling. All Grades included Grades 1-4.
Number of Participants With Cycle Delay and/or Dose Modification Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks) A theoretical cycle is a 2 week period i.e. 14 days. A cycle is delayed if duration of previous cycle is greater than 14+2 days ; dose modification includes dose reduction and dose omission.
Number of Participants With Abnormal Non-Gradable Biochemistry Parameters Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks) Non-gradeable biochemistry parameters included; chloride, urea, total protein, blood urea nitrogen (BUN) and lactate dehydrogenase (LDH). Number of participants with \<lower limit of normal ranges (LLN) and \>upper limit of normal ranges (ULN) for each of these parameters were reported.
Number of Participants With Proteinuria Grade >=2 Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks) Proteinuria is defined as the ratio of protein to creatinine. Number of participants with proteinuria grade \>=2 (graded as per NCI CTCAE Version 4.03), where Grade\>=2 represents moderate to life-threatening/disabling event.
Number of Participants With Proteinuria Events Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks) Proteinuria is defined as the ratio of protein to creatinine. Number of participants with proteinuria were analyzed by grades (Grades 1, 2, 3 ,4) as per NCI CTCAE Version 4.03 where Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling.
Number of Participants With Urinary Protein-Creatinine Ratio (UPCR) Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks) Urinary protein creatinine ratio (UPCR) corresponds to the ratio of the urinary protein and urinary creatinine concentration (expressed in mg/dL). This ratio provides an accurate quantification of 24-hours urinary protein excretion. There is a high correlation between morning UPCR and 24-hour proteinuria in participants with normal or reduced renal functions. Normal ratio is \< or = 1.
Number of Participants With Proteinuria (Grade>=2) Concomitant With Hematuria and /or Hypertension Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks) Proteinuria is defined as the presence of excess proteins in the urine (assessed either by spot sample, dipstick/ urine protein or 24 hour urine collection). Hematuria is defined as the presence of blood in urine (positive dipstick for RBC or reported AE). Number of participants with proteinuria grade \>=2 (graded as per NCI CTCAE Version 4.03), where Grade\>=2 represents moderate to life-threatening/disabling event. Hypertension (high blood pressure) is defined as having a blood pressure reading of more than 140/90 mmHg over a number of weeks.
- Secondary Outcome Measures
Name Time Method Mean 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 Score): Global Health Status Pre-dose at Baseline, Day 1 of every odd cycle (from Cycle 3 to 35); at the end of treatment (EOT) (within 30 days of last treatment) (maximum exposure: 214 weeks) 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 favourable outcome with a best quality of life for participant.
Change From Baseline in HRQL EORTC QLQ-C30 Score: Symptom Scales Pre-dose at Baseline, Day 1 of every odd cycle (from Cycle 3 to 35); at EOT (within 30 days of last treatment) (maximum exposure: 214 weeks) 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.
Mean Change From Baseline in HRQL EORTC QLQ-C30 Score: Functional Scales Pre-dose at Baseline, Day 1 of every odd cycle (from Cycle 3 to 35); at EOT (within 30 days of last treatment) (maximum exposure: 214 weeks) 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 favourable outcome with a best quality of life for participant.
Change From Baseline in HRQL EQ-5D-3L VAS Score Pre-dose at Baseline, Day 1 of every odd cycle (from Cycle 3 to 35); at EOT (within 30 days of last treatment) (maximum exposure: 214 weeks) EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and 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. The VAS recorded the respondent's self-rated health on a vertical visual analogue scale. The VAS 'thermometer' has endpoints of 100 (Best imaginable health state) at the top and 0 (Worst imaginable health state) at the bottom. This information can be used as a quantitative measure of health outcome as judged by the individual respondents.
Change From Baseline in HRQL EQ-5D-3L Quality of Life: Single Index Utility Score Pre-dose at Baseline, Day 1 of every odd cycle (from Cycle 3 to 35); at EOT (within 30 days of last treatment) (maximum exposure: 214 weeks) 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.
Trial Locations
- Locations (179)
Investigational Site Number 840-002
🇺🇸Muscle Shoals, Alabama, United States
Investigational Site Number 840-008
🇺🇸Corona, California, United States
Investigational Site Number 840-007
🇺🇸Fountain Valley, California, United States
Investigational Site Number 840-004
🇺🇸Riverside, California, United States
Investigational Site Number 840-006
🇺🇸Indianapolis, Indiana, United States
Investigational Site Number 840-011
🇺🇸Metairie, Louisiana, United States
Investigational Site Number 840-001
🇺🇸Rockville, Maryland, United States
Investigational Site Number 840-010
🇺🇸Howell, New Jersey, United States
Investigational Site Number 840-012
🇺🇸Albuquerque, New Mexico, United States
Investigational Site Number 840-009
🇺🇸Farmington, New Mexico, United States
Scroll for more (169 remaining)Investigational Site Number 840-002🇺🇸Muscle Shoals, Alabama, United States