OPTIMOX-aflibercept as First-line Therapy in Patients With Unresectable Metastatic Colorectal Cancer

NCT ID: NCT01802684

Last Updated: 2017-03-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2016-06-30

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.

Conditions

Unresectable Metastatic Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

OPTIMOX-aflibercept

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

Group Type: EXPERIMENTAL

aflibercept

Intervention Type: BIOLOGICAL

Aflibercept (VEGF Trap) Recombinant human protein, at 25 mg/ml Dose : 4 mg/Kg -Day 1, q2w Route of administration: Intravenous (60 min infusion)

Interventions

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)

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

GERCOR - Multidisciplinary Oncology Cooperative Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Benoist Chibaudel, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Saint Antoine

Locations

Polyclinique de Bordeaux Nord

Bordeaux, , France

Hôpital Henri Mondor

Créteil, , France

CHU Dupuytren

Limoges, , France

Hôpital Privé Jean Mermoz

Lyon, , France

CH Mont de Marsan

Paris, , France

Hôpital Saint-Antoine

Paris, , France

Hôpital Pitié Salpêtrière

Paris, , France

Institut Mutualiste Montsouris

Paris, , France

Countries

France

Other Identifiers

2012-003521-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VELVET C12-1

Identifier Type: -

Identifier Source: org_study_id