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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
ClinicalTrials.gov Identifier:
NCT01802684
First received: February 26, 2013
Last updated: August 12, 2014
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Unresectable Metastatic Colorectal Cancer
Biological: aflibercept
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: OPTIMOX-aflibercept as First-line Therapy in 49 Patients With Unresectable Metastatic Colorectal Cancer. A GERCOR Feasibility Single-arm Phase II Study.

Resource links provided by NLM:


Further study details as provided by Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR):

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

    DDC excludes:

    • Intervals between disease progression and re-initiation of treatment,
    • PFS of inactive treatment if PD occurs at first evaluation after treatment re-initiation

  • 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. ] [ Designated as safety issue: No ]
  • tumor Response Rate (RR) [ Time Frame: Assessed every 2 months during treatment period (- Estimated treatment duration per patient : 16 months). ] [ Designated as safety issue: No ]
    assessed using RECIST version 1.1 per sequence of therapy.

  • 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. ] [ Designated as safety issue: No ]
    EORTC QLQ C-30

  • 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 ] [ Designated as safety issue: No ]

    The study will take into account all adverse events observed during and after drug administration, with a particular interest for:

    • Any AE
    • Any AE related to study treatment
    • Any serious AE
    • Any serious AE related to study treatment
    • Any NCI-CTC grade 3 or 4 AE
    • Any NCI-CTC grade 3 or 4 AE related to study treatment
    • Any AE causing discontinuation of study treatment
    • Any AE causing discontinuation of selected treatment only
    • Any AE related to study treatment causing discontinuation
    • Any AE causing a dose reduction of study medication
    • Any AE leading to death
    • Any AE related to study treatment leading to death.

  • Curative salvage surgery [ Time Frame: assessed up to 3 years after the beginning of the study ] [ Designated as safety issue: No ]
    The number of patient with R0 and R1 curative salvage surgery will be assessed globally and per sequence of therapy.


Estimated Enrollment: 49
Study Start Date: May 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Biological: 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)

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01802684

Locations
France
Polyclinique de Bordeaux Nord
Bordeaux, France, 33300
Hôpital Henri Mondor
Créteil, France, 94010
CHU Dupuytren
Limoges, France, 87042
Hôpital Privé Jean Mermoz
Lyon, France, 69008
Hôpital Pitié Salpêtrière
Paris, France, 75013
Hôpital Saint-Antoine
Paris, France, 75012
Institut Mutualiste Montsouris
Paris, France, 75014
CH Mont de Marsan
Paris, France, 40000
Sponsors and Collaborators
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
Sanofi
Investigators
Principal Investigator: Benoist Chibaudel, MD Hôpital Saint Antoine
  More Information

No publications provided

Responsible Party: Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
ClinicalTrials.gov Identifier: NCT01802684     History of Changes
Other Study ID Numbers: VELVET C12-1, 2012-003521-25
Study First Received: February 26, 2013
Last Updated: August 12, 2014
Health Authority: France: ANSM - French Competent Authority

Keywords provided by Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR):
unresectable
metastatic
colorectal
cancer
OPTIMOX
aflibercept

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on August 19, 2014