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Colorectal NeoplasmsPhase 2FOLFANCT02384759

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

A Phase 2 study testing aflibercept and LV5FU2 in people with Colorectal Neoplasms, run by Federation Francophone de Cancerologie Digestive at 58 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 65 years and older
Conditions the study is for
Colorectal Neoplasms
What is being tested?
aflibercept and LV5FU2
Could I receive a placebo?
No, everyone receives an active treatment
How many people
117 participants
Where
58 sitesFrance
Study dates
May 2015to Jun 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

58 sites in 1 country.

58 sites in 1 country

France58 sites

  • CH

    Aix-en-Provence

  • CHU Amiens - Hôpital Nord

    Amiens, 80054

  • Chu D'Angers

    Angers, 49933

  • ICO

    Angers

  • CH

    Auxerre

  • CH de la Côte Basque

    Bayonne, 64109

  • Centre D'Oncologie Et de Radiothérapie

    Bayonne

  • CH

    Béziers

  • Hôpital Avicenne

    Bobigny, 93000

  • CHU APHP Hôpital Avicenne

    Bobigny

  • CHU- Hôpital Saint André

    Bordeaux

  • Polyclinique Bordeaux Nord

    Bordeaux

  • CH - Hôpital Duchenne

    Boulogne-sur-Mer

  • CH

    Brive-la-Gaillarde

  • CHU Côte de Nacre

    Caen

  • Ch

    Chambéry

  • CH Public du Cotentin

    Cherbourg

  • CHU Estaing

    Clermont-Ferrand

  • CH Alpes Leman

    Contamine-sur-Arve

  • Centre hospitalier Sud Francilien

    Corbeil-Essonnes, 91106

  • Institut de cancérologie de Bourgogne - GRRECC

    Dijon, 21000

  • CHU Le Bocage

    Dijon

  • CH

    Elbeuf

  • Chicas

    Gap

  • CHD Vendée

    La Roche-sur-Yon

  • CH Robert Boulin

    Libourne

  • Clinique François Chénieux

    Limoges, 87000

  • CHU

    Limoges

  • Ch Longjumeau

    Longjumeau, 91160

  • CH Hôpital du Surcoff

    Lorient

  • Ch Saint Joseph - Saint Luc

    Lyon

  • CHU APHM Hôpital Nord

    Marseille

  • CHU APHM La Timone

    Marseille

  • Hôpital Européen de Marseille

    Marseille

  • CH

    Meaux

  • CH

    Montélimar

  • CHU - Hôtel Dieu

    Nantes

  • Polyclinique de Languedoc

    Narbonne

  • CHR La Source

    Orléans, 45067

  • Saint-Louis CHU AP-HP Paris

    Paris, 75010

  • CH

    Perpignan

  • Hôpital Haut Leveque

    Pessac, 33604

  • CHU Hôpital de la Milétrie

    Poitiers

  • Centre Hospitalier Annecy Genevois

    Pringy

  • Centre Eugène Marquis

    Rennes

  • CHU

    Rouen

  • CARIO - Hôpital Privé des Côte d'Armor

    Saint-Brieuc

  • ICO

    Saint-Herblain

  • Polyclinique Côte Basque Sud

    Saint-Jean-de-Luz

  • Ch Saintonges

    Saintes

  • Centre de cancérologie Paris Nord

    Sarcelles

  • CH de Bigorre

    Tarbes

  • Hôpitaux du Leman

    Thonon-les-Bains

  • CHU Hôpital Rangueil

    Toulouse

  • Hôpital Trousseau

    Tours

  • CHBA

    Vannes

  • Institut Gustave Roussy

    Villejuif

  • Hôpital Privé de Villeneuve d'Ascq

    Villeneuve-d'Ascq

Other trials in France

About this study

Official title: Phase II Randomized Trial Evaluting Aflibercept Associated With LV5FU2 Regimen as First Line Treatment of Non-resectalbe Metastatic Colorectal Cancers

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.

Read the 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).

Being tested
aflibercept, LV5FU2
Keywords
cancer, colorectal,
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • afliberceptDrug

    Also called zaltrap

  • LV5FU2Drug

Study groups in NCT02384759
Study groupRoleWhat they receive
AExperimentalAflibercept + LV5FU2
Receives: Drug: aflibercept; Drug: LV5FU2
BActive comparatorLV5FU2
Receives: Drug: LV5FU2

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Primary Objective Was the Percentage of Patients Alive and Without Progression 6 Months After the Randomization.

    Progression was assessed by the investigator according to RECIST 1.1 criteria based on imaging studies performed every 8 weeks, even in case of deferred treatments. Clinical progressions, not confirmed on imaging, were not be counted in the primary endpoint

    Measured: At 6 months after randomization

Secondary outcomes (2)

  1. Overall Survival (OS)

    Overall survival was defined as the time from the date of randomization to the patient's death (all causes). For alive patients, the date of the latest news was taken into account

    Measured: Up to 3 years after the treatment start

  2. Progression-free Survival (PPFS)

    It was defined as the time between t randomization and the date of the first radiological progression (RECIST 1.1 criteria) according to the investigator or death; Patients alive without progression were censored at the date of last news

    Measured: up to 12 months after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Mar 2015 (estimated)
  2. Study startMay 2015
  3. Primary completionJun 2021
  4. Study completionJun 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
117 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02384759
Sponsor's protocol ID
PRODIGE25
Acronym
FOLFA
Status last verified
Jul 2024
First submitted
28 Jan 2015
Last updated
10 Jul 2024
Data monitoring committee
Yes

Publications

  • Legoux JL, Faroux R, Barriere N, Le Malicot K, Tougeron D, Lorgis V, Guerin-Meyer V, Bourgeois V, Malka D, Aparicio T, Baconnier M, Lebrun-Ly V, Egreteau J, Khemissa Akouz F, Terme M, Lepage C, Boige V. First-Line LV5FU2 with or without Aflibercept in Patients with Non-Resectable Metastatic Colorectal Cancer: A Randomized Phase II Trial (PRODIGE 25-FFCD-FOLFA). Cancers (Basel). 2024 Apr 16;16(8):1515. doi: 10.3390/cancers16081515.

    PubMed 38672597

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing aflibercept and LV5FU2 in people with Colorectal Neoplasms, run by Federation Francophone de Cancerologie Digestive at 58 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Primary Objective Was the Percentage of Patients Alive and Without Progression 6 Months After the Randomization. (time frame: At 6 months after randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02384759, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2024.

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