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

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ClinicalTrials.gov Identifier: NCT01678664
Recruitment Status : Completed
First Posted : September 5, 2012
Last Update Posted : March 30, 2020
Sponsor:
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive

Tracking Information
First Submitted Date  ICMJE August 22, 2012
First Posted Date  ICMJE September 5, 2012
Last Update Posted Date March 30, 2020
Actual Study Start Date  ICMJE October 2012
Actual Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 5, 2016)
Rate of hepatic progression free survival at 24 months [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 30, 2012)
Rate of hepatic progression free survival at 24 months [ Time Frame: 24 months after the last included patient ]
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 5, 2016)
  • Progression free survival rate (hepatic or not) at 24 months [ Time Frame: 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.
  • Overall survival rate [ Time Frame: 24 months ]
    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.
  • Toxicities treatment [ Time Frame: 24 months ]
    the toxicities recorded at each monthly visit, described using -CTCAE version 4.0; grade 3 and 4 toxicities will be reviewed;
Original Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2012)
  • Progression free survival rate (hepatic or not) at 24 months [ Time Frame: 24 months after the last included patient ]
    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.
  • Overall survival rate [ Time Frame: 24 months after the last included patient ]
    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.
  • Toxicities treatment [ Time Frame: 24 months after the last included patient ]
    the toxicities recorded at each monthly visit, described using -CTCAE version 4.0; grade 3 and 4 toxicities will be reviewed;
  • Safety [ Time Frame: 24 months after the last included patient ]
    the number and description of SAEs;
  • Tolerability of the treatment [ Time Frame: 24 months after the last included patient ]
    the duration of treatment, the doses received, dose reductions, and deferred administrations;
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Everolimus After (Chemo)Embolization for Liver Metastases From Digestive Endocrine Tumors
Official Title  ICMJE Everolimus as Treatment After Embolization or Chemoembolization for Liver Metastases From Digestive Endocrine Tumors
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%
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neuroendocrine Tumors
  • Hepatic Metastases
  • Metastases
Intervention  ICMJE
  • Drug: Everolimus
    10 mg per day of everolimus during 24 months or until progression disease
  • Device: embolization
    2 sessions embolization with spheric particles
    Other Name: spheric particules of 100 to 500 µm
  • Drug: Doxorubicin
    2 sessions chemoembolization with 10 mg of lipiodol with 100 mg of doxorubicine
    Other Name: Chemoembolization
Study Arms  ICMJE Experimental: 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).
Interventions:
  • Drug: Everolimus
  • Device: embolization
  • Drug: Doxorubicin
Publications * 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 Baère 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 2, 2016)
74
Original Estimated Enrollment  ICMJE
 (submitted: August 30, 2012)
72
Actual Study Completion Date  ICMJE April 2019
Actual Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01678664
Other Study ID Numbers  ICMJE FFCD 1104
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Federation Francophone de Cancerologie Digestive
Study Sponsor  ICMJE Federation Francophone de Cancerologie Digestive
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Thomas WALTER, PhD Hôpital Edouard Herriot - Lyon
PRS Account Federation Francophone de Cancerologie Digestive
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP