Everolimus After (Chemo)Embolization for Liver Metastases From Digestive Endocrine Tumors

Neuroendocrine Tumors Clinical Trial

— EVACEL  

Official title:

Everolimus as Treatment After Embolization or Chemoembolization for Liver Metastases From Digestive Endocrine Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01678664
• Other study ID #: FFCD 1104
• Status: Completed
• Phase: Phase 2
• Start date: October 2012
• Est. completion date: April 2019

Study information

• Verified date: March 2020
• Source: Federation Francophone de Cancerologie Digestive
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: April 2019
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Endocrine Gland Neoplasms
• Hepatic Metastases
• Metastases
• Neoplasm Metastasis
• Neoplasms, Second Primary
• Neuroendocrine Tumors

Intervention

Drug:
• Everolimus
10 mg per day of everolimus during 24 months or until progression disease

Device:
• embolization
2 sessions embolization with spheric particles

Drug:
• Doxorubicin
2 sessions chemoembolization with 10 mg of lipiodol with 100 mg of doxorubicine

Locations

Country	Name	City	State
France	CHU - Hôtel Dieu	Angers
France	Hôpital Avicenne	Bobigny
France	Hôpital Saint André	Bordeaux
France	Hôpital Côte de Nacre	Caen
France	CHU - Estaing	Clermont Ferrand
France	Hôpital Beaujon	Clichy
France	Centre GF Leclerc	Dijon
France	CHU - Hôpital François Mitterand	Dijon
France	Hôpital Edouard Herriot	Lyon
France	CHU La Timone	Marseille
France	CHR	Orléans
France	CHU Cochin	Paris
France	Hôpital Européen Georges Pompidou	Paris
France	Hôpital Robert Debré	Reims
France	CHU	Rouen
France	Hôpital Rangueil	Toulouse
France	Hôpital Trousseau	Tours
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Federation Francophone de Cancerologie Digestive

Country where clinical trial is conducted

France, 

References & Publications (1)

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, Lo — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of hepatic progression free survival at 24 months	Hepatic progression free survival rate as defined in RECIST 1.1 (with death considered as progression) during the 24 months of treatment with everolimus (appendix 3).; Progression-free survival rate (PFS) (based on the central assessment) according to RECIST v1.1 according to RECIST v1.1 will be defined as the time from the date of inclusion to the date of hepatic progression or death (due to any cause). For patients who are alive with no hepatic progression, it will be defines as the time from the date of inclusion and the date of the last tumor assessment.	24 months
Secondary	Progression free survival rate (hepatic or not) at 24 months	Progression-free survival rate will be defined as the time from the date of inclusion to the date of disease progression (hepatic or not) evaluated by RECIST V1.1 criteria or death (due to any cause) or the date of the last morphological evaluation for patients who are alive with no disease progression.	24 months
Secondary	Overall survival rate	Overall survival rate shall be defined as the time from the date of inclusion to the date of death, regardless of the cause of death, or the date of last contact for patients who are alive.	24 months
Secondary	Toxicities treatment	the toxicities recorded at each monthly visit, described using -CTCAE version 4.0; grade 3 and 4 toxicities will be reviewed;	24 months