Overview

This trial is active, not recruiting.

Conditions neuroendocrine tumors, hepatic metastases, metastases
Treatments everolimus, embolization, doxorubicin
Phase phase 2
Targets mTOR, FKBP-12
Sponsor Federation Francophone de Cancerologie Digestive
Start date October 2012
End date April 2017
Trial size 74 participants
Trial identifier NCT01678664, FFCD 1104

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%

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(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).
everolimus
10 mg per day of everolimus during 24 months or until progression disease
embolization spheric particules of 100 to 500 µm
2 sessions embolization with spheric particles
doxorubicin Chemoembolization
2 sessions chemoembolization with 10 mg of lipiodol with 100 mg of doxorubicine

Primary Outcomes

Measure
Rate of hepatic progression free survival at 24 months
time frame: 24 months

Secondary Outcomes

Measure
Progression free survival rate (hepatic or not) at 24 months
time frame: 24 months
Overall survival rate
time frame: 24 months
Toxicities treatment
time frame: 24 months

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Everolimus as Treatment After Embolization or Chemoembolization for Liver Metastases From Digestive Endocrine Tumors
Principal investigator Thomas WALTER, PhD
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Federation Francophone de Cancerologie Digestive.