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

Overview[ - collapse ][ - ]

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%
ConditionNeuroendocrine Tumors
Hepatic Metastases
Metastases
InterventionDrug: Everolimus
Device: embolization
Drug: Doxorubicin
PhasePhase 2
SponsorFederation Francophone de Cancerologie Digestive
Responsible PartyFederation Francophone de Cancerologie Digestive
ClinicalTrials.gov IdentifierNCT01678664
First ReceivedAugust 22, 2012
Last UpdatedJanuary 2, 2013
Last verifiedJanuary 2013

Tracking Information[ + expand ][ + ]

First Received DateAugust 22, 2012
Last Updated DateJanuary 2, 2013
Start DateOctober 2012
Estimated Primary Completion DateApril 2017
Current Primary Outcome MeasuresRate 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.
Current 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;

Descriptive Information[ + expand ][ + ]

Brief TitleEverolimus After (Chemo)Embolization for Liver Metastases From Digestive Endocrine Tumors
Official TitleEverolimus 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 DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 2
Study DesignEndpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Neuroendocrine Tumors
  • Hepatic Metastases
  • Metastases
InterventionDrug: Everolimus
10 mg per day of everolimus during 24 months or until progression disease
Device: embolization
2 sessions embolization with spheric particles
Other Names:
spheric particules of 100 to 500 µmDrug: Doxorubicin
2 sessions chemoembolization with 10 mg of lipiodol with 100 mg of doxorubicine
Other Names:
Chemoembolization
Study Arm (s)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).

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment72
Estimated Completion DateApril 2017
Estimated Primary Completion DateApril 2017
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
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Emmanuel MITRY, PhD
+33 (0)1 47 11 15 29
emmanuel.mitry@curie.net
Location CountriesFrance

Administrative Information[ + expand ][ + ]

NCT Number NCT01678664
Other Study ID NumbersFFCD 1104
Has Data Monitoring CommitteeYes
Information Provided ByFederation Francophone de Cancerologie Digestive
Study SponsorFederation Francophone de Cancerologie Digestive
CollaboratorsNot Provided
Investigators Principal Investigator: Emmanuel MITRY, PhD Institut Curie
Verification DateJanuary 2013

Locations[ + expand ][ + ]

Fédération Francophone de Cancérologie Digestive
Dijon, Côte d'Or, France, 21000
Contact: Marie MOREAU | +33 (0)3 80 39 34 04 | marie.moreau@u-bourgogne.fr
Sub-Investigator: Come LEPAGE, PhD
Recruiting