Overview

This trial is active, not recruiting.

Condition unresectable metastatic colorectal cancer
Treatment aflibercept
Phase phase 2
Target VEGF
Sponsor Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
Collaborator Sanofi
Start date May 2013
End date March 2016
Trial size 49 participants
Trial identifier NCT01802684, 2012-003521-25, VELVET C12-1

Summary

Evaluation of feasibility of adding aflibercept to an oxaliplatin-based regimen rather than a continuous administration of chemotherapy until progression, in order to decrease the risk of severe toxicities.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Induction therapy (sequence #1) Regimen : aflibercept + modified FOLFOX7 Duration : 6 cycles (3 months) Maintenance after induction (sequence #2) First phase (sequence #2A) Regimen : aflibercept + fluoropyrimidine (simplifed LV5FU2 or capecitabine) Duration : 6 cycles (3 months) Second phase (sequence #2B) Regimen : aflibercept +/- fluoropyrimidine (simplifed LV5FU2 or capecitabine) according to eligibility criteria for chemotherapy-free interval) Duration : until PD or limiting toxicity Reintroduction (sequence #3) Regimen : aflibercept + modified FOLFOX7 Duration : 6 cycles (3 months) Maintenance after reintroduction (sequence #4) Regimen : aflibercept + fluoropyrimidine Duration : until PD or limiting toxicity
aflibercept
Aflibercept (VEGF Trap) Recombinant human protein, at 25 mg/ml Dose : 4 mg/Kg -Day 1, q2w Route of administration: Intravenous (60 min infusion)

Primary Outcomes

Measure
Progression free survival at 6 months
time frame: time interval from inclusion to the date of first documented disease progression or death from any cause, whichever occurs first. Assessed at 6 months.

Secondary Outcomes

Measure
Median Progression Free Survival
time frame: time interval from inclusion to the date of first documented disease progression or death from any cause, whichever occurs first. Assessed up to 3 years after the beginning of the study
duration of disease control (DDC)
time frame: sum of PFS of each active treatment course. Assessed up to 3 years after the beginning of the study
Overall Survival
time frame: time interval from inclusion to the date of death from any cause. Assessed up to 3 years after the beginning of the study.
tumor Response Rate (RR)
time frame: Assessed every 2 months during treatment period (- Estimated treatment duration per patient : 16 months).
Health related Quality of life
time frame: Assessed from study entry to 1 month after last study drug administration and up to 3 years after the beginning of the study.
Safety
time frame: Assessed from study entry to 1 month after last study drug administration, assessed up to 3 years after the beginning of the study
Curative salvage surgery
time frame: assessed up to 3 years after the beginning of the study

Eligibility Criteria

Male or female participants at least 18 years old.

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. No prior therapy for metastatic disease (in case of previous adjuvant therapy, interval from end of chemotherapy to relapse must be >6 months for fluoropyrimidine alone or >12 months for oxaliplatin-based, bevacizumab-based, cetuximab-based therapy, 5. Duly documented inoperable metastatic disease, ie not suitable for complete carcinological surgical resection, 6. At least one measurable or evaluable lesion as assessed by CT-scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1, 7. Age ≥18 years, 8. ECOG Performance status (PS) 0-2, 9. Hematological status: neutrophils (ANC) ≥1.5x109/L; platelets ≥100x109/L; haemoglobin ≥9g/dL, 10. Adequate renal function: serum creatinine level <150µM, 11. Adequate liver function: serum bilirubin ≤3 x upper normal limit (ULN), alkaline phosphatase <5xULN, 12. Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour, 13. Baseline evaluations: clinical and blood evaluations performed no more than 2 weeks (14 days) prior to confirmation of eligibility, tumor assessment (chest X ray, CT-scan or MRI, evaluation of non-measurable lesions) no more than 3 weeks (21 days) prior to confirmation of eligibility, 14. For female patients of childbearing potential, negative serum or urine pregnancy test within 1 week (7 days) prior of starting study treatment, 15. Female patients of childbearing potential must commit to using reliable and effective methods of contraception during the trial and until at least six months after the end of study treatment. Females are neither pregnant nor in breastfeeding. Male patients with a partner of childbearing potential must agree to use effective contraception in addition to the contraceptive method used by their partner during the trial and until at least six months after the end of study treatment. 16. Registration in a national health care system (CMU included for France). Exclusion Criteria: 1. 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), 2. Exclusive bone metastasis, 3. Uncontrolled hypercalcemia, 4. Pre-existing permanent neuropathy (NCI grade ≥2), 5. Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg despite optimal medical therapy), or history of hypertensive crisis, or hypertensive encephalopathy, 6. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy/ radio-immunotherapy), 7. Treatment with any other investigational medicinal product within 28 days prior to study entry, 8. Other serious and uncontrolled non-malignant disease, 9. Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years, 10. Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days 11. Patients with known allergy to any excipient to study drugs, 12. History of myocardial infarction and/or stroke within 6 months prior to study entry, 13. Bowel obstruction.

Additional Information

Official title OPTIMOX-aflibercept as First-line Therapy in 49 Patients With Unresectable Metastatic Colorectal Cancer. A GERCOR Feasibility Single-arm Phase II Study.
Principal investigator Benoist Chibaudel, MD
Description The addition of aflibercept to the standard FOLFIRI regimen as second-line therapy was evaluated in a large phase III study (EFC10262-VELOUR). This new combination significantly improved both PFS (4.7 to 6.9 months, HR=0.76; P=.00007) and OS (12.1 to 13.5 months, HR=0.82; P=.0032). In the evaluable population (86.5%), the tumor response rate was also improved when adding aflibercept (ORR=19.8% [16.4-23.2]) to the FOLFIRI regimen (ORR=11.1% [8.5-13.8]). This trial will evaluate the feasibility of adding aflibercept to an oxaliplatin-based regimen as a first-line therapy , using the OPTIMOX strategy rather than a continuous administration of chemotherapy until progression, in order to decrease the risk of severe toxicities.
Trial information was received from ClinicalTrials.gov and was last updated in December 2015.
Information provided to ClinicalTrials.gov by Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR).