ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.

Type d'étude
Présentation de l'étude
Acronyme : NEXT-REGIRI

Nom :

Traitement : Métastatique ou localement avancé

Type d'étude : Ciblage moléculaire / Innovation thérapeutique

Dernière MÀJ : 21/01/2020
CIM10 - Localisation(s)
Informations principales
Titre : Etude de phase III evaluant la combinaison régorafénib+irinotecan (REGIRI) versus régorafénib seul chez des patients atteints d’un CCRm en échec aux thérapies standards avec un génotype A/A de la cycline D1

Spécialité : Organes digestifs
Localisation : C18 - Tumeur maligne du côlon

Spécialité : Organes digestifs
Localisation : C20 - Tumeur maligne du rectum
Informations complémentaires
Schéma : A Phase III randomized trial that compared Nexiri (Nexavar® + Irinotecan) vs irinotecan or versus Sorafenib alone showed a progression-free survival at two-months which was favorable to the NEXIRI combination ; 59% ( IC95% : 39-66 ) versus 23% (IC95% : 10-33) and 22% (IC95%: 8-30) respectively.

The patients treated with Irinotecan or Sorafenib alone could receive NEXIRI combination after progression and the progression-free survivals were 3,7 months (IC95% : 2,2-4,9) and 3,5 months (IC95% : 2,1-3,7) in patients treated with NEXIRI or after progression and 1,9 months (IC95% : 1,7-2,1) and 2,1 months (IC95% : 1,9-2,5) in patients treated only with Irinotecan and Sorafenib respectively.

The median overall survival was higher with NEXIRI : 7,2 months (patients treated from the beginning of the study) and 7,9 months (patients treated after progression and crossover) versus 3 months in patients treated only with Irinotecan and 3,2 months in patients receiving only Sorafenib.

The A870A rs603965 polymorphism of cyclin D1, a molecule involved in the initiation of cell division, was favorable to the NEXIRI combination on overall survival with a median of 19.6 months versus 6.2 months for two other genotypes A/G and G/G.

Regorafenib, which is an oral signal deactivation agent with a chemical structure very similar to Sorafenib, is a standard treatment in heavily pretreated mCRC patients since the results of CORRECT study which compared Regorafenib to placebo on overall survival showed a superiority of Regorafenib : 6,4 months versus 5 months (HR 0,774 [IC95% 0,63, 0,94]).

Sorafenib isn't approved in mCRC so the objective of this NEXT-REGIRI trial is compared REGIRI combination (Regorafenib-Irinotecan) to Regorafenib alone in a phase III trial in patients in progression after having received all standard treatments and bearing genotype A/A of cyclin D1

Phase : III

Stade : Métastasique

2, 3, 4, X
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion :
Signed informed consent obtained before any study specific procedures
Male or female ≥ 18 years of age
Histological or cytological documentation of adenocarcinoma of the colon or rectum
Patients with metastatic colorectal cancer
Progression during or within 3 months following the last administration of approved standard therapies, which must include a fluoropyrimidine (or raltitrexed), oxaliplatin, irinotecan, anti VEGF therapy and an anti EGFR therapy (for RAS wild-type tumors)
ECOG performance status ≤1
Life expectancy of at least 3 months
Patients with A/A CCND1 genotype of rs603965 CCND1
Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: Amylase and lipase ≤1.5 x ULN,Total bilirubin ≤ 1.5 x ULN,Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer), Alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5.0 x ULN for patients with liver involvement for their cancer and/or have bone metastases), Platelet count ≥ 100,000/mm3; Hemoglobin (Hb) ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥ 1,500/ mm3. Transfusion to meet the inclusion criterion, Serum creatinine ≤ 1.5 x ULN
International normalized ratio (INR) ≤ 1.5 x ULN and partialthromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment with therapeutic anticoagulation. Patients being treated with anticoagulant, e.g., heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care
Women of childbearing potential must have a blood or urine pregnancy test performed a maximum of 7 days before start of study treatment, and a negative result must be documented before start of study treatment
Women of childbearing potential and men must agree to use adequate contraception before entering the study until at least 8 weeks after the last study drug administration of Regorafenib and 12 weeks after the last study drug administration of Irinotecan. The investigator or a designated associate is requested to advise the patient on how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care.

Critères de non-inclusion :
Patients with A/G or G/G CCND1 genotype of rs603965 CCND1
Prior treatment with regorafenib or sorafenib
Prior treatment with TAS 102
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study drug
Pregnant or breast-feeding subjects. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of study drug
Congestive heart failure ≥ New York Heart Association (NYHA) class 2
Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months)
Myocardial infarction less than 6 months before start of study drug
Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
Uncontrolled hypertension. (Systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg despite optimal medical management)
Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE V5.0 Grade 2 dyspnea)
Ongoing infection > Grade 2 NCI-CTCAE V5.0
Known history of human immunodeficiency virus (HIV) infection
Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy
Patients with seizure disorder requiring medication
History of organ allograft
Patients with evidence or history of any bleeding diathesis, irrespective of severity
Any hemorrhage or bleeding event ≥ NCI-CTC V5.0 Grade 3 within 4 weeks prior to the start of study medication
Non-healing wound, ulcer, or bone fracture
Dehydration NCI-CTCAE V5.0 Grade ≥ 1
Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results
Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation
Any illness or medical conditions that are unstable or could
jeopardize the safety of the subject and his/her compliance in the study
Persistent proteinuria of NCI-CTCAE V5.0 Grade 3 (> 3.5g/24 hours)
Patients unable to swallow oral medications
Any malabsorption condition
Chronic inflammatory bowel disease and / or bowel obstruction
Unresolved toxicity higher than NCI-CTCAE V.5.0 Grade 1 attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced neurotoxicity ≤ Grade 2
Concomitant participation or participation within the last 30 days in another clinical trial
Systemic anticancer therapy during this trial or within 4 weeks before randomization
Concomitant intake of st John's wort
Live attenuated vaccines are prohibited 10 days before the treatment, during the treatment and 6 months after the termination of treatment
History of gastrointestinal fistula or perforation
Informations relatives au promoteur
Promoteur :
Institut du Cancer de Montpellier - Val d'Aurelle
Type de sponsor : Institutionnel
Institut du Cancer de Montpellier - Val d'Aurelle

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre François BACLESSE - 3 avenue du Général Harris - 14000 CAEN
Apicrypt :

Investigateur :
Marie-Pierre GALAIS

Corentin LE GALLIC

Statut de l'essai : OUVERT

MAJ : 21/01/2020