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FOLFA: Aflibercept +/- LV5FU2 in First Line of Non-resectalbe Metastatic Colorectal Cancers

Sponsor
Federation Francophone de Cancerologie Digestive (Other)
Overall Status
Completed
CT.gov ID
NCT02384759
Collaborator
(none)
117
Enrollment
58
Locations
2
Arms
73
Duration (Months)
2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is what the FFCD 11-01 - PRODIGE 25 trial proposes to study, as a preliminary for strategic studies evaluating the usefulness of including targeted therapeutics from the first line with aflibercept +/- LV5FU2.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

The aflibercept-5-FU combination has never been evaluated as yet. Aflibercept, at a dose of 4 mg/kg, has already been used in combination with 5-FU at the doses used in the simplified LV5FU2 regimen (folinic acid 400 mg/m2 IV in 90 min, then 5-FU 400 mg/m2 IV bolus on D1, followed by continuous perfusion of 5-FU 2,400 mg/m2 in 46h) (23) as part of the above-mentioned VELOUR trial, evaluating its combination with FOLFIRI (= simplified LV5FU2 + irinotecan). This trial was preceded by a phase I trial validating the doses used (24). It is therefore not necessary to perform a phase I trial if you use the same doses of 5-FU without irinotecan, within the context of a strategy for reducing toxicity in patients to be treated over a long period, and not search for the maximum tolerated dose of the combination.

The aflibercept-LV5FU2 combination can be useful for patients who will never be resectable or operable, and for whom 5-FU monotherapy can be suggested to delay the toxicities of combined chemotherapies. Within this context, it is possible for aflibercept to provide a survival benefit. The previous VELOUR trial (18) did not indicate that toxicity would have a major effect on quality of life and increase the hope of prolonged progression-free survival in the arm with aflibercept.

This is what the FFCD 11-01 - PRODIGE 25 trial proposes to study, as a preliminary for strategic studies evaluating the usefulness of including targeted therapeutics from the first line.

This trial will evaluate the efficacy of the combination and its tolerance by studying toxicities and quality of life. Quality of life will be studied via the EORTC questionnaire QLQ-C30.

The thymidylate synthase polymorphism type 2R2R-2R3R versus 3R3R seems to predict greater efficacy of 5-FU monotherapy. Stratification in this criterion will confirm or negate the prognostic or predictive nature of 5-FU efficacy linked to these polymorphisms.

The draft version of this trial has been studied and evaluated by the scientific council of the Fédération Francophone de Cancérologie Digestive (FFCD) then the Digestive Group of the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) within the framework of their Partnership for Research in Digestive Oncology (PRODIGE cooperation).

Study Design

Study Type:
Interventional
Actual Enrollment :
117 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Randomized Trial Evaluting Aflibercept Associated With LV5FU2 Regimen as First Line Treatment of Non-resectalbe Metastatic Colorectal Cancers
Study Start Date :
May 1, 2015
Actual Primary Completion Date :
Jun 1, 2021
Actual Study Completion Date :
Jun 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: A

Aflibercept + LV5FU2

Drug: aflibercept
Other Names:
  • zaltrap

    • Drug: LV5FU2
    Active Comparator: B

    LV5FU2

    Drug: LV5FU2

    Outcome Measures

    Primary Outcome Measures

    1. Radiological progression-free survival according to the investigator [up to 6 months]

    Secondary Outcome Measures

    1. Overall survival [up to the end of the follow-up or death (whatever the cause)]

    2. progression-free survival [up to the end of the follow-up or occurence of progression or death (whatever the cause)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    65 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Age ≥ 65 years

    • General condition WHO ≤ 2

    • Metastatic rectal or colonic adenocarcinoma, histologically proved on the primary tumour or a metastasis

    • Metastases non-resectable and/or patient inoperable

    • patients where a single agent chemotherapy combined with an anti-angiogenic agent is an appropriate approach

    • At least one measurable target according to RECIST v1.1 criteria, no previously irradiated

    • No previous treatment of the metastatic disease. Previous chemotherapy in an adjuvant situation completed 6 months or more before diagnosis of the metastasis is authorized.

    • Adequate biological examination: Hb > or = 9 g/dl, polynuclear neutrophils > or = 1,500/mm3, platelets > or =100,000/mm3, total bilirubin < or = 1.5 x UNL, creatinine clearance, calculated according to Cockroft-Gault formula, > 50 ml/min creatininemia < 1.5 x UNL, ALP < 5 x UNL, transaminases < 5 x ULN, GGT< 5 x UNL

    • Proteinuria (strip) < 2+; if > or = 2+, test proteinuria over 24 hours which must be ≤ 1 g.

    • Central genotyping of thymidylate synthase (TS) in blood DNA

    • Patients treated with anticoagulants (coumadin, warfarin) can be included if the INR can be closely monitored. A change in anticoagulant treatment for low molecular weight heparin is preferable in order to respect indications

    • Signed written informed consent obtained prior to inclusion

    Exclusion Criteria:

    • Patients with a primary tumour in place and presenting clinical symptoms (occlusion, haemorrhage)

    • History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.

    • Uncontrolled hypercalcemia

    • Uncontrolled hypertension (SBP > 150 mmHg and DBP > 100 mmHg) or history of hypertensive attacks or hypertensive encephalopathy

    • Any progressive pathology not balanced over the past 6 months: hepatic insufficiency, renal insufficiency, respiratory insufficiency,

    • Any of the following within 6 months prior to inclusion: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack.

    • Any of the following within 3 months prior to inclusion: Grade 3-4 gastrointestinal bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event, wound or fractured bone

    • Major surgery during the 28 days preceding the start of treatment

    • Known acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease requiring antiretroviral treatment.

    • Treatment with concomitant anticonvulsivant agents that are CYP3A4 inducers (phenytoin, phenobarbital, carbamazepine), unless discontinued >7 days.

    • Anti-tumoral treatments other than the trial treatments (chemotherapy, targeted therapy, immunotherapy)

    • Macronodular peritoneal carcinosis (risk of perforation)

    • Known DPD deficit

    • Prior history of malignant haemopathy or cancer except those treated more than 5 years ago and considered to be cured, in situ cervical carcinomas and treated skin cancers (excluding melanoma)

    • Patients on new oral anticoagulant therapy (rivaroxaban XARELTOR, apixaban ELIQUIS, dagigatran PRADAXA except if relay by vitamine K antagonist therapy)

    • Any contraindication to the treatments used in the trial

    • Impossibility of undergoing medical monitoring during the trial for geographic, social or psychological reasons

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 CH Aix En Provence France
    2 CHU Amiens - Hôpital Nord Amiens CEDEX 1 France 80054
    3 Chu D'Angers Angers France 49933
    4 ICO Angers France
    5 CH Auxerre France
    6 CH de la Côte Basque Bayonne France 64109
    7 Centre D'Oncologie Et de Radiothérapie Bayonne France
    8 Hôpital Avicenne Bobigny France 93000
    9 CHU APHP Hôpital Avicenne Bobigny France
    10 CHU- Hôpital Saint André Bordeaux France
    11 Polyclinique Bordeaux Nord Bordeaux France
    12 CH - Hôpital Duchenne Boulogne Sur Mer France
    13 CH Brive La Gaillarde France
    14 CH Béziers France
    15 CHU Côte de Nacre Caen France
    16 Ch Chambery France
    17 CH Public du Cotentin Cherbourg France
    18 CHU Estaing Clermont Ferrand France
    19 CH Alpes Leman Contamine Sur Arve France
    20 Centre hospitalier Sud Francilien Corbeil-Essonnes France 91106
    21 Institut de cancérologie de Bourgogne - GRRECC Dijon France 21000
    22 CHU Le Bocage Dijon France
    23 CH Elbeuf France
    24 Chicas Gap France
    25 CHD Vendée La Roche Sur Yon France
    26 CH Robert Boulin Libourne France
    27 Clinique François Chénieux Limoges France 87000
    28 CHU Limoges France
    29 Ch Longjumeau Longjumeau France 91160
    30 CH Hôpital du Surcoff Lorient France
    31 Ch Saint Joseph - Saint Luc Lyon France
    32 CHU APHM Hôpital Nord Marseille France
    33 CHU APHM La Timone Marseille France
    34 Hôpital Européen de Marseille Marseille France
    35 CH Meaux France
    36 CH Montelimar France
    37 CHU - Hôtel Dieu Nantes France
    38 Polyclinique de Languedoc Narbonne France
    39 CHR La Source Orleans France 45067
    40 Saint-Louis CHU AP-HP Paris Paris France 75010
    41 CH Perpignan France
    42 Hôpital Haut Leveque Pessac CEDEX France 33604
    43 CHU Hôpital de la Milétrie Poitiers France
    44 Centre Hospitalier Annecy Genevois Pringy France
    45 Centre Eugène Marquis Rennes France
    46 CHU Rouen France
    47 ICO Saint Herblain France
    48 Polyclinique Côte Basque Sud Saint Jean De Luz France
    49 CARIO - Hôpital Privé des Côte d'Armor Saint-Brieuc France
    50 Ch Saintonges Saintes France
    51 Centre de cancérologie Paris Nord Sarcelles France
    52 CH de Bigorre Tarbes France
    53 Hôpitaux du Leman Thonon Les Bains France
    54 CHU Hôpital Rangueil Toulouse France
    55 Hôpital Trousseau Tours France
    56 CHBA Vannes France
    57 Institut Gustave Roussy Villejuif France
    58 Hôpital Privé de Villeneuve d'Ascq Villeneuve d'Ascq France

    Sponsors and Collaborators

    • Federation Francophone de Cancerologie Digestive

    Investigators

    • Principal Investigator: Jean Louis LEGOUX, MD, ORLEANS - Centre Hospitalier La Source

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Federation Francophone de Cancerologie Digestive
    ClinicalTrials.gov Identifier:
    NCT02384759
    Other Study ID Numbers:
    • PRODIGE25
    First Posted:
    Mar 10, 2015
    Last Update Posted:
    Apr 4, 2022
    Last Verified:
    Mar 1, 2022
    Keywords provided by Federation Francophone de Cancerologie Digestive
    cancer, colorectal,
    Additional relevant MeSH terms:
    Colorectal Neoplasms
    Aflibercept

    Study Results

    No Results Posted as of Apr 4, 2022