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

NCT ID: NCT02384759

Last Updated: 2024-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 117 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2021-06-30

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.

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).

Conditions

Colorectal Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Aflibercept + LV5FU2

Group Type: EXPERIMENTAL

aflibercept

Intervention Type: DRUG

LV5FU2

Intervention Type: DRUG

B

LV5FU2

Group Type: ACTIVE_COMPARATOR

LV5FU2

Intervention Type: DRUG

Interventions

aflibercept

Intervention Type: DRUG

LV5FU2

Intervention Type: DRUG

Other Intervention Names

zaltrap

Eligibility Criteria

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

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federation Francophone de Cancerologie Digestive

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean Louis LEGOUX, MD

Role: PRINCIPAL_INVESTIGATOR

ORLEANS - Centre Hospitalier La Source

Locations

CH

Aix-en-Provence, , France

CHU Amiens - Hôpital Nord

Amiens, , France

Chu D'Angers

Angers, , France

ICO

Angers, , France

CH

Auxerre, , France

CH de la Côte Basque

Bayonne, , France

Centre D'Oncologie Et de Radiothérapie

Bayonne, , France

CH

Béziers, , France

Hôpital Avicenne

Bobigny, , France

CHU APHP Hôpital Avicenne

Bobigny, , France

CHU- Hôpital Saint André

Bordeaux, , France

Polyclinique Bordeaux Nord

Bordeaux, , France

CH - Hôpital Duchenne

Boulogne-sur-Mer, , France

CH

Brive-la-Gaillarde, , France

CHU Côte de Nacre

Caen, , France

Ch

Chambéry, , France

CH Public du Cotentin

Cherbourg, , France

CHU Estaing

Clermont-Ferrand, , France

CH Alpes Leman

Contamine-sur-Arve, , France

Centre hospitalier Sud Francilien

Corbeil-Essonnes, , France

Institut de cancérologie de Bourgogne - GRRECC

Dijon, , France

CHU Le Bocage

Dijon, , France

CH

Elbeuf, , France

Chicas

Gap, , France

CHD Vendée

La Roche-sur-Yon, , France

CH Robert Boulin

Libourne, , France

Clinique François Chénieux

Limoges, , France

CHU

Limoges, , France

Ch Longjumeau

Longjumeau, , France

CH Hôpital du Surcoff

Lorient, , France

Ch Saint Joseph - Saint Luc

Lyon, , France

CHU APHM Hôpital Nord

Marseille, , France

CHU APHM La Timone

Marseille, , France

Hôpital Européen de Marseille

Marseille, , France

CH

Meaux, , France

CH

Montélimar, , France

CHU - Hôtel Dieu

Nantes, , France

Polyclinique de Languedoc

Narbonne, , France

CHR La Source

Orléans, , France

Saint-Louis CHU AP-HP Paris

Paris, , France

CH

Perpignan, , France

Hôpital Haut Leveque

Pessac, , France

CHU Hôpital de la Milétrie

Poitiers, , France

Centre Hospitalier Annecy Genevois

Pringy, , France

Centre Eugène Marquis

Rennes, , France

CHU

Rouen, , France

CARIO - Hôpital Privé des Côte d'Armor

Saint-Brieuc, , France

ICO

Saint-Herblain, , France

Polyclinique Côte Basque Sud

Saint-Jean-de-Luz, , France

Ch Saintonges

Saintes, , France

Centre de cancérologie Paris Nord

Sarcelles, , France

CH de Bigorre

Tarbes, , France

Hôpitaux du Leman

Thonon-les-Bains, , France

CHU Hôpital Rangueil

Toulouse, , France

Hôpital Trousseau

Tours, , France

CHBA

Vannes, , France

Institut Gustave Roussy

Villejuif, , France

Hôpital Privé de Villeneuve d'Ascq

Villeneuve-d'Ascq, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 38672597 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PRODIGE25

Identifier Type: -

Identifier Source: org_study_id