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

NCT01678664 | Completed Phase 2 Results DMC

• 1 other identifier: FFCD 1104
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 18

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

Keywords

cancer; neuroendocrine tumors; gastrointestinal tract; metastases; liver; hepatic

Outcome Measures

Primary Outcomes (1)

• 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. Progression-free survival rate (PFS) (based on the investigator) 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.

  Up to 24 months

Secondary Outcomes (2)

• Progression-free Survival (Hepatic or Not)

  From randomization until the date of first progression (clinical or radiological) or death from any cause whichever came first, assessed up to 3 years

• Overall Survival

  From randomization until death or last news for alive patients

Study Arms (1)

embolization or chemoembolization plus everolimus

EXPERIMENTAL

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).

Drug: Everolimus; Device: embolization; Drug: Doxorubicin

Interventions

Everolimus DRUG

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

embolization or chemoembolization plus everolimus

embolization DEVICE

2 sessions embolization with spheric particles

Also known as: spheric particules of 100 to 500 µm

embolization or chemoembolization plus everolimus

Doxorubicin DRUG

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

Also known as: Chemoembolization

embolization or chemoembolization plus everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Federation Francophone de Cancerologie Digestive: lead

Study Sites (18)

CHU - Hôtel Dieu

Angers, France

Location

Hôpital Avicenne

Bobigny, France

Location

Hôpital Saint André

Bordeaux, France

Location

Hôpital Côte de Nacre

Caen, France

Location

CHU - Estaing

Clermont-Ferrand, France

Location

Hôpital Beaujon

Clichy, France

Location

Centre GF Leclerc

Dijon, France

Location

CHU - Hôpital François Mitterand

Dijon, France

Location

Hôpital Edouard Herriot

Lyon, France

Location

CHU La Timone

Marseille, France

Location

CHR

Orléans, France

Location

CHU Cochin

Paris, France

Location

Hôpital Européen Georges Pompidou

Paris, France

Location

Hôpital Robert Debré

Reims, France

Location

CHU

Rouen, France

Location

Hôpital Rangueil

Toulouse, France

Location

Hôpital Trousseau

Tours, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Related 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, 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.

  PMID: 31678771 RESULT

MeSH Terms

Conditions

Neuroendocrine Tumors; Neoplasm Metastasis; Neoplasms

Interventions

Everolimus; Embolization, Therapeutic; Doxorubicin; Chemoembolization, Therapeutic

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Hemostatic Techniques; Therapeutics; Therapeutic Occlusion; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Karine Le Malicot
• Organization: Fédération Francophone de Cancérologie Digestive

karine.le-malicot@u-bourgogne.fr

+33 3 80 39 34 79

Study Officials

• Thomas WALTER, PhD

  Hôpital Edouard Herriot - Lyon

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2012
• First Posted: September 5, 2012
• Study Start: December 1, 2012
• Primary Completion: September 1, 2018
• Study Completion: April 1, 2019
• Last Updated: September 25, 2024
• Results First Posted: September 25, 2024

Record last verified: 2024-09

Locations

FR (18)