Clinical trial NCT01802684: OPTIMOX-aflibercept as First-line Therapy in Patients With Unresectable Metastatic Colorectal Cancer
Official title: OPTIMOX-aflibercept as First-line Therapy in 49 Patients With Unresectable Metastatic Colorectal Cancer. A GERCOR Feasibility Single-arm Phase II Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Unresectable Metastatic Colorectal Cancer
Keywords: unresectable
metastatic
colorectal
cancer
OPTIMOX
aflibercept
Lead sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2013-03-01
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression free survival at 6 months
timeFrame: 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
timeFrame: 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
measure: duration of disease control (DDC)
timeFrame: sum of PFS of each active treatment course. Assessed up to 3 years after the beginning of the study
measure: Overall Survival
timeFrame: time interval from inclusion to the date of death from any cause. Assessed up to 3 years after the beginning of the study.
measure: tumor Response Rate (RR)
timeFrame: Assessed every 2 months during treatment period (- Estimated treatment duration per patient : 16 months).
measure: Health related Quality of life
timeFrame: Assessed from study entry to 1 month after last study drug administration and up to 3 years after the beginning of the study.
measure: Safety
timeFrame: Assessed from study entry to 1 month after last study drug administration, assessed up to 3 years after the beginning of the study
measure: Curative salvage surgery
timeFrame: assessed up to 3 years after the beginning of the study
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Polyclinique de Bordeaux Nord
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Limoges
country: France
facility: CHU Dupuytren
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Paris
country: France
facility: CH Mont de Marsan
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Paris
country: France
facility: Hôpital Pitié Salpêtrière
city: Paris
country: France
facility: Institut Mutualiste Montsouris
Study officials:
affiliation: Hôpital Saint Antoine
name: Benoist Chibaudel, MD
role: PRINCIPAL_INVESTIGATOR
References: