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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Federation Francophone de Cancerologie Digestive
Sponsor:
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier:
NCT01678664
First received: August 22, 2012
Last updated: January 2, 2013
Last verified: January 2013
  Purpose

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%

Condition Intervention Phase
Neuroendocrine Tumors
Hepatic Metastases
Metastases
Drug: Everolimus
Device: embolization
Drug: Doxorubicin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Everolimus as Treatment After Embolization or Chemoembolization for Liver Metastases From Digestive Endocrine Tumors

Resource links provided by NLM:


Further study details as provided by Federation Francophone de Cancerologie Digestive:

Primary Outcome Measures:
  • Rate of hepatic progression free survival at 24 months [ Time Frame: 24 months after the last included patient ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Progression free survival rate (hepatic or not) at 24 months [ Time Frame: 24 months after the last included patient ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    the number and description of SAEs;

  • Tolerability of the treatment [ Time Frame: 24 months after the last included patient ] [ Designated as safety issue: Yes ]
    the duration of treatment, the doses received, dose reductions, and deferred administrations;


Estimated Enrollment: 72
Study Start Date: October 2012
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01678664

Contacts
Contact: Emmanuel MITRY, PhD +33 (0)1 47 11 15 29 emmanuel.mitry@curie.net
Contact: Marie MOREAU +33 (0)3 80 39 34 04 marie.moreau@u-bourgogne.fr

Locations
France
Fédération Francophone de Cancérologie Digestive Recruiting
Dijon, Côte d'Or, France, 21000
Contact: Marie MOREAU    +33 (0)3 80 39 34 04    marie.moreau@u-bourgogne.fr   
Contact: Martina SCHNEIDER    +33 (0)3 80 66 80 13    martina.schneider@u-bourgogne.fr   
Sub-Investigator: Come LEPAGE, PhD         
Sponsors and Collaborators
Federation Francophone de Cancerologie Digestive
Investigators
Principal Investigator: Emmanuel MITRY, PhD Institut Curie
  More Information

No publications provided

Responsible Party: Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier: NCT01678664     History of Changes
Other Study ID Numbers: FFCD 1104
Study First Received: August 22, 2012
Last Updated: January 2, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Committee for the Protection of Personnes

Keywords provided by Federation Francophone de Cancerologie Digestive:
cancer
neuroendocrine tumors
gastrointestinal tract
metastases
liver
hepatic

Additional relevant MeSH terms:
Endocrine Gland Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Neuroendocrine Tumors
Liver Neoplasms
Neoplasms by Site
Neoplasms
Endocrine System Diseases
Neoplastic Processes
Pathologic Processes
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases
Doxorubicin
Liposomal doxorubicin
Sirolimus
Everolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents

ClinicalTrials.gov processed this record on August 28, 2014