Status:
UNKNOWN
TWICE-IRI: Optimization of Second-line Therapy With Aflibercept, Irinotecan (Day 1 or Day 1,3), 5-Fluorouracile and Folinic Acid in Patients With Metastatic Colorectal Cancer. A Randomized Phase III Study.
Lead Sponsor:
Hôpital Franco-Britannique-Fondation Cognacq-Jay
Collaborating Sponsors:
Fondation ARCAD
Conditions:
Cancer Colorectal
Metastasis
Eligibility:
All Genders
18+ years
Phase:
PHASE3
Brief Summary
Optimization of second-line therapy with aflibercept, irinotecan (day1 or day 1,3), 5fluorouracile and folinic acid in patients with metastatic colorectal cancer. A randomized Phase III study.
Detailed Description
Background - Rationale Aflibercept The addition of aflibercept to the standard FOLFIRI regimen as second-line therapy was evaluated in a large phase III study (EFC10262-VELOUR). This combination signi...
Eligibility Criteria
Inclusion
- Provision of signed and dated informed consent and stated willingness to comply with all study procedures and availability for the duration of the study, Signed, written Informed Consent Form (ICF),
- Willing and able to comply with the protocol,
- Age 18-75 years,
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1,
- Life expectancy ≥ 3 months,
- Histologically proven carcinoma of colon and/or rectum,
- Confirmed unresectable metastatic disease,
- At least one measurable and/or evaluable tumor metastasis on CT-scan or MRI per RECIST criteria version 1.1,
- Prior oxaliplatin-based first-line therapy for metastatic disease (the use of prior bevacizumab or anti-EGFR mabs is allowed but not mandatory) - Less than 6 months from completion of any prior oxaliplatin-based adjuvant therapy can be considered as first-line therapy. Prior use of irinotecan in combination with oxaliplatin and 5FU as first-line therapy is allowed if the interval between the last administration of irinotecan and disease progression is at least 6 months (ie, irinotecan-free interval ≥6 months).
- Negative urine and/or serum pregnancy test within 7 days before inclusion if female subject is of childbearing potential,
- Clinical laboratory parameters adequate as follows:
- Serum total bilirubin level ≤ 1.5 x upper normal limit (UNL),
- Neutrophil count ≥ 1.5x109/L,
- Platelet count ≥ 100x109/L,
- Hemoglobin ≥ 9 g/dL,
- Serum creatinine level ≤ 150µM,
- Serum albumin ≥ 25 g/L,
- Calcium ≥ 1 x ULN
- Alkaline phosphatase (ALP) \< 3 x ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3 x ULN (in the case of liver metastases, \<5 x ULN),
- Proteinuria \<2+ (dipstick urinalysis) or ≤1g/24hour,
- For women of childbearing potential and for men, agreement to use an effective contraceptive method from the time of screening throughout the study until 6 months after administration of the last dose of any study medication. Highly effective contraceptive method consist of prior sterilization, inter-uterine device, intrauterine hormone-releasing system, oral or injectable contraceptives barrier methods, and/or true sexual abstinence),
- Affiliation to French health care system.
Exclusion
- History of arterial thrombotic event in the last 6 months (eg., myocardial infarction, cerebrovascular accident or transient ischemic attack),
- Uncontrolled hypertension (defined as systolic blood pressure \> 140 mmHg and/or diastolic blood pressure \> 90 mmHg despite optimal medical therapy), or history of hypertensive crisis, or hypertensive encephalopathy,
- Prior use of aflibercept,
- Adverse events from prior anticancer therapy grade ≥2 (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] version 5.0), except for neuropathy and alopecia,
- Bowel obstruction, inflammatory bowel disease
- Known DPD deficiency. If not known for the patient, testing for DPD should be done during the screening period (patients with uracilemia ≥16ng/mL are not eligible),
- Known UGT1A1 deficiency (eg, Gilbert syndrome, Crigler-Najjar syndrome). If not known for the patient, genetic testing for UGT1A1 should be done during the screening period for patients with hyperbilirubinemia (ie, total bilirubin level \>1xULN),
- Active infection requiring intravenous antibiotics at the start of study treatment,
- Known active infection with human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV),
- Known allergy or hypersensitivity to the active substance or ingredients of any study drug,
- Women currently pregnant or breastfeeding,
- Inability to comply with study and follow-up procedures as judged by the Investigator,
- Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy)
- Concomitant use of Saint John Wort herb (millepertuis), Yellow Fever vaccine, Live Attenuated Vaccines (LAV) and phenytoine
- Treatment with any other investigational medicinal product within 28 days or 5 investigational agent half-lives (whichever is longer) prior to the start of study treatment,
- Any other disease, active, uncontrolled bacterial, viral or fungal infection requiring systemic therapy, metabolic dysfunction, physical examination finding or clinical laboratory finding that leads to reasonable suspicion of a disease or condition that contraindicates the use of study drugs that may affect the interpretation of the results, or that may render the subject at high risk for treatment complications.
- Previous or concurrent malignancy, except for adequately treated basal or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for three years prior to study entry,
- Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to start of study treatment, or anticipation of need for major surgical procedure during the course of the study.
- Minor surgical procedure including placement of a vascular access device, within 2 days of start of study treatment,
- History of abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to start study treatment.
- Clinically significant active cardiac disease (including NYHA class III or IV congestive heart failure)
- Venous thromboembolic event (including pulmonary embolism) grade 3 or 4 within 6 months prior to start study treatment.
Key Trial Info
Start Date :
September 2 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
June 1 2024
Estimated Enrollment :
202 Patients enrolled
Trial Details
Trial ID
NCT04392479
Start Date
September 2 2020
End Date
June 1 2024
Last Update
October 23 2023
Active Locations (1)
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1
Franco-British Hospital - GCS IHFB Cognacq-Jay
Levallois-Perret, France, 92300