Clinical trial NCT01678664: Everolimus After (Chemo)Embolization for Liver Metastases From Digestive Endocrine Tumors
Official title: Everolimus as Treatment After Embolization or Chemoembolization for Liver Metastases From Digestive Endocrine Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroendocrine Tumors
Hepatic Metastases
Metastases
Keywords: cancer
neuroendocrine tumors
gastrointestinal tract
metastases
liver
hepatic
Lead sponsor: Federation Francophone de Cancerologie Digestive
Sponsor class: OTHER
First posted: 2012-09-05
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Determine wether 24 months treatment with everolimus prolongs progression free survival rate (based on a central assessment) after embolisation ou chemoembolisation for liver metastases.

* H0 a 24 months progression free survival rate less than 35% is unacceptable
* H1 a 24 months progression free survival rate greater than 35% would show that everolimus treatment is beneficial, the expected 24 months progression free survival rate being 50%


Eligibility criteria: Inclusion Criteria:

* Well differentiated (grade 1 and 2 according to WHO classification 2010 appendix 2), histologically-proven endocrine tumor of the gastrointestinal tract (TENpath review mandatory),
* Measurable liver metastasis (or metastases) as defined in RECIST v1.1 that are unresectable and inaccessible to radiofrequency ablation-type local treatment
* Hepatic arterial embolization or chemoembolization indicated for tumor size reduction, confirmed in an multidisciplinary team (MDT) meeting, due to the progressive nature of the liver metastases (morphological progression during the past 12 months as defined in RECIST v1.1)
* Age ≥ 18 years
* WHO performance status ≤ 2
* No contraindications to embolization or chemoembolization or everolimus
* Satisfactory laboratory assessments:Neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, Hb \> 10 g/dL, serum bilirubin ≤ 1.5 x the upper limit of normal (ULN), INR \< 1.3 (or \< 3 for patients on anticoagulant therapy) ALT and AST ≤ 5 x ULN, creatinine ≤ 1.5 x ULN, fasting serum cholesterol ≤ 300 mg/dL or 7.75 mmol/L and triglycerides ≤ 2.5 x ULN (if either or both of these limits are exceeded, the patient may only be included into the study after institution of appropriate lipid-lowering therapy)
* Complete resolution of toxic effects of any prior treatments, or persistence at grade 1 at most (CTCAE version 4.0)
* Minimum time since previous treatment: 28 days
* Patient has been informed and has signed an informed consent form, after verification of the eligibility criteria
* Patient covered by a French national health insurance scheme

Exclusion Criteria:

* Duodenopancreatic neuroendocrine tumor
* Poorly differentiated and/or grade 3 endocrine tumor,
* Embolization or chemoembolization indicated for symptomatic control only
* Prior hepatic TACE or embolization
* Prior treatment with an mTOR inhibitor (somatostatin analogs to control secretion are permitted)
* Symptomatic bone metastasis (or metastases)
* Any uncontrolled progressive disease: hepatic failure, renal failure, respiratory failure, NYHA class III-IV congestive heart failure, unstable angina, myocardial infarction, significant arrhythmia
* Interstitial lung disease
* Uncontrolled diabetes, defined by HbA1c \> 8%
* Chronic corticosteroid or immunosuppressant therapy
* Hypersensitivity to everolimus, other rapamycin derivatives, or one of the excipients
* Major surgery, open biopsy, or significant traumatic lesion during the 28 days prior to starting the investigational treatment Incompletely healed wound or foreseeable need for major surgery during the study
* Contraindication to vascular occlusion procedures: Portal thrombosis, biliodigestive anastomosis
* Malignancy during the past 5 years, with the exception of curatively treated basal cell skin carcinoma or in situ cervical cancer
* Foreseeable non-compliance
* Medical, geographic, sociological, psychological, or legal situation that would preclude the patient from completing the study or signing an informed consent form
* Pregnant or breast-feeding women
* Men or women of child-bearing potential not using effective contraception
* Concurrent participation in another investigational study that could affect the primary endpoint of this study

Primary outcomes:
measure: Rate of Hepatic Progression Free Survival at 24 Months
timeFrame: Up to 24 months
Secondary outcomes:
measure: Progression-free Survival (Hepatic or Not)
timeFrame: From randomization until the date of first progression (clinical or radiological) or death from any cause whichever came first, assessed up to 3 years
measure: Overall Survival
timeFrame: From randomization until death or last news for alive patients
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU - Hôtel Dieu
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bordeaux
country: France
facility: Hôpital Saint André
city: Caen
country: France
facility: Hôpital Côte de Nacre
city: Clermont Ferrand
country: France
facility: CHU - Estaing
city: Clichy
country: France
facility: Hôpital Beaujon
city: Dijon
country: France
facility: Centre GF Leclerc
city: Dijon
country: France
facility: CHU - Hôpital François Mitterand
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Marseille
country: France
facility: CHU La Timone
city: Orléans
country: France
facility: CHR
city: Paris
country: France
facility: CHU Cochin
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Reims
country: France
facility: Hôpital Robert Debré
city: Rouen
country: France
facility: CHU
city: Toulouse
country: France
facility: Hôpital Rangueil
city: Tours
country: France
facility: Hôpital Trousseau
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Hôpital Edouard Herriot - Lyon
name: Thomas WALTER, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Walter T, Lepage C, Coriat R, Barbier E, Cadiot G, Caroli-Bosc FX, Aparicio T, Bouhier-Leporrier K, Hentic-Dhome O, Gay F, Dupont-Gossart AC, Duluc M, Lepere C, Lecomte T, Smith D, Petorin C, Di-Fiore F, Ghiringhelli F, Legoux JL, Guimbaud R, Baudin E, Lombard-Bohas C, de Baere T; FFCD 1104 investigators/investigators. Everolimus after hepatic arterial embolisation therapy of metastases from gastrointestinal neuroendocrine tumours: The FFCD 1104-EVACEL-GTE phase II study. Eur J Cancer. 2019 Dec;123:92-100. doi: 10.1016/j.ejca.2019.09.021. Epub 2019 Oct 31.