Metastatic Colorectal Cancer
Conditions
Keywords
metastatic colorectal cancer, FOLFIRI, aflibercept, oxaliplatin, ACE polymorphisms
Brief summary
The purpose of this study is to assess FOLFIRI+aflibercept efficacy in patients with or without ACE polymorphisms in terms of Progression-free survival (PFS).
Interventions
DRUGFOLFIRI+aflibercept
Aflibercept: 4 mg/kg administered intravenous infusion on day 1 FOLFIRI regimen immediately after aflibercept: Irinotecan:180 mg/m2 intravenous infusion, folinic acid (dl racemic): 400 mg/m2 intravenous infusion, followed by 5-fluorouracil (5-FU): 400 mg/m2 intravenous bolus, followed by 5-FU: 2400 mg/m2 continuous intravenous infusion over 46 hours. \* folinic acid: 400 mg/m² (racémic) or 200 mg/m² (L-form)
Sponsors
Sanofi
Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed and dated informed consent, and willing and able to comply with protocol requirements, 2. Histologically proven adenocarcinoma of the colon and/or rectum, 3. Metastatic disease confirmed. 4. Existence of at least one measurable unidimensional lesion using CT or MRI based on the RECIST criteria, version 1.1 5. Patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed after an oxaliplatin-containing regimen. 6. Age ≥18 years 7. World Health Organization (WHO) Performance status (PS) 0-2, 8. Hematological status: neutrophils (ANC) ≥1.5x109 /L; platelets ≥100x109 /L; haemoglobin ≥9g/dL 9. Adequate renal function: serum creatinine level \< 1.5 x ULN 10. Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline phosphatase (ALP) \<5xULN 11. Proteinuria \<2+ (dipstick urinalysis) or ≤1g/24hour. 12. Regular follow-up feasible. 13. For female patients of childbearing potential, negative serum pregnancy test 14. Female patients must commit to using reliable and appropriate methods of contraception until at least three months after the end of study treatment (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method during the trial.
Exclusion criteria
1. Uncontrolled hypercalcemia, 2. Pre-existing permanent neuropathy (NCI grade \>2) 3. Uncontrolled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg), or history of hypertensive crisis, or hypertensive ncephalopathy, 4. Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy), 5. Treatment with any other investigational medicinal product within 28 days prior to study entry. 6. Other serious and uncontrolled non-malignant disease, 7. History or evidence upon physical examination of CNS metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy), 8. Known Gilbert's syndrome 9. Intolerance to atropine sulfate or loperamide 10. Known dihydropyrimidine dehydrogenase deficiency 11. Treatment with CYP3A4 inducers unless discontinued \> 7 days prior to inclusion 12. Any of the following in 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis. 13. Other concomitant or previous malignancy, except: i/ adequately treated insitu carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for \>5 years, 14. Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days 15. Pregnant or breastfeeding women, 16. Patients with known allergy to any excipient to study drugs, 17. History of myocardial infarction and/or stroke within 6 months prior to inclusion, NYHA class III and IV congestive heart failure 18. Bowel obstruction.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| FOLFIRI+aflibercept efficacy in terms of Progression-free survival (PFS) with or without ACE polymorphisms. | 30 months |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival (PFS) with or without AGTR1 polymorphisms, according Serum-level sACE | 30 months |
| Objective Response Rate (ORR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE | 30 months |
| Disease Control Rate (DCR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE | 30 months |
| Time to progression (TP) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE | 30 months |
| Overall survival (OS) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE | 30 months |
| Number of participants with adverse events as assessed by CTCAE v4.0. | 30 months |
| Time to treatment failure (TTF) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE | 30 months |
Other
| Measure | Time frame |
|---|---|
| Plasma VEGF levels circulating and their correlation with tumour-efficacy parameters (ORR, PFS and OS) | 30 months |
| Other biomarkers in serum and tumour tissue associated with cell and tumour growth and/or involved in the mechanism of action of FOLFIRI+aflibercept and their correlation with tumour-efficacy parameters (ORR, PFS and OS) | 30 months |
Countries
Spain
Outcome results
None listed