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

NCT ID: NCT01678664

Last Updated: 2024-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2019-04-30

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%

Conditions

Neuroendocrine Tumors; Hepatic Metastases; Metastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

embolization or chemoembolization plus everolimus

After 2 sessions of embolization with microsphere of 100 to 500 µm or chemoembolization with 100 mg of doxorubicine and 10 ml of lipiodol, administered every day, 10 mg of everolimus during 24 months or until progression (hepatic and other site).

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

10 mg per day of everolimus during 24 months or until progression disease

embolization

Intervention Type: DEVICE

2 sessions embolization with spheric particles

Doxorubicin

Intervention Type: DRUG

2 sessions chemoembolization with 10 mg of lipiodol with 100 mg of doxorubicine

Interventions

Everolimus

10 mg per day of everolimus during 24 months or until progression disease

Intervention Type: DRUG

embolization

2 sessions embolization with spheric particles

Intervention Type: DEVICE

Doxorubicin

2 sessions chemoembolization with 10 mg of lipiodol with 100 mg of doxorubicine

Intervention Type: DRUG

Other Intervention Names

spheric particules of 100 to 500 µm; Chemoembolization

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

• Minimum Eligible Age: 18 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

Thomas WALTER, PhD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Edouard Herriot - Lyon

Locations

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, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 31678771 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

FFCD 1104

Identifier Type: -

Identifier Source: org_study_id