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

NCT01802684 | Completed Phase 2 DMC

• 2 other identifiers: VELVET C12-12012-003521-25
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 8

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.

Conditions

Unresectable Metastatic Colorectal Cancer

Keywords

unresectable; metastatic; colorectal; cancer; OPTIMOX; aflibercept

Outcome Measures

Primary Outcomes (1)

• Progression free survival at 6 months

  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 (7)

• Median Progression Free Survival

  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)

  sum of PFS of each active treatment course. Assessed up to 3 years after the beginning of the study

• Overall Survival

  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)

  Assessed every 2 months during treatment period (- Estimated treatment duration per patient : 16 months).

• Health related Quality of life

  Assessed from study entry to 1 month after last study drug administration and up to 3 years after the beginning of the study.

Study Arms (1)

OPTIMOX-aflibercept

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

Biological: aflibercept

Interventions

aflibercept 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)

OPTIMOX-aflibercept

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent, and willing and able to comply with protocol requirements,
• Histologically proven adenocarcinoma of the colon and/or rectum,
• Metastatic disease confirmed,
• 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,
• Duly documented inoperable metastatic disease, ie not suitable for complete carcinological surgical resection,
• At least one measurable or evaluable lesion as assessed by CT-scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1,
• Age ≥18 years,
• ECOG Performance status (PS) 0-2,
• Hematological status: neutrophils (ANC) ≥1.5x109/L; platelets ≥100x109/L; haemoglobin ≥9g/dL,
• Adequate renal function: serum creatinine level \<150µM,
• Adequate liver function: serum bilirubin ≤3 x upper normal limit (ULN), alkaline phosphatase \<5xULN,
• Proteinuria \<2+ (dipstick urinalysis) or ≤1g/24hour,
• 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,
• For female patients of childbearing potential, negative serum or urine pregnancy test within 1 week (7 days) prior of starting study treatment,
• 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.

You may not qualify if:

• 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),
• Exclusive bone metastasis,
• Uncontrolled hypercalcemia,
• Pre-existing permanent neuropathy (NCI grade ≥2),
• 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,
• Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy/ radio-immunotherapy),
• Treatment with any other investigational medicinal product within 28 days prior to study entry,
• Other serious and uncontrolled non-malignant disease,
• 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,
• Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days
• Patients with known allergy to any excipient to study drugs,
• History of myocardial infarction and/or stroke within 6 months prior to study entry,
• Bowel obstruction.

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead
• Sanofi: collaborator

Study Sites (8)

Polyclinique de Bordeaux Nord

Bordeaux, 33300, France

Location

Hôpital Henri Mondor

Créteil, 94010, France

Location

CHU Dupuytren

Limoges, 87042, France

Location

Hôpital Privé Jean Mermoz

Lyon, 69008, France

Location

CH Mont de Marsan

Paris, 40000, France

Location

Hôpital Saint-Antoine

Paris, 75012, France

Location

Hôpital Pitié Salpêtrière

Paris, 75013, France

Location

Institut Mutualiste Montsouris

Paris, 75014, France

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Benoist Chibaudel, MD

  Hôpital Saint Antoine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2013
• First Posted: March 1, 2013
• Study Start: May 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: June 1, 2016
• Last Updated: March 1, 2017

Record last verified: 2017-02

Locations

FR (8)