Clinical trial NCT02333565: Combination of Everolimus and Octreotide LAR in Aggressive Recurrent Meningiomas
Official title: Combination of Everolimus and Octreotide LAR in Aggressive Recurrent Meningiomas.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Meningiomas
Resistant Meningiomas
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2015-01-07
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To determine if combination of everolimus and octreotide exert an anti-tumoral activity in recurrent and/or aggressive meningiomas growth with limited adverse effects.


Eligibility criteria: Inclusion Criteria:

* Male and Female patients ≥ 18 years old with no maximum limited of age
* Histologically proven meningioma grade II and III; grade I meningioma may also be included, if progression is documented (see criteria 3), particularly in case of skull base location
* Progression is defined on 2 different MRI as an increase of meningioma's surface ≥ 5% by 3 months period (i.e. an increase of 5% over 3 months, 10% over 6 months, 15% over 9 months...) or as the apparition of a new unequivocal neurological symptom related to the meningioma. We considered as a new unequivocal neurological symptom a new occurring neurological symptom as, for instance, hemiparesia, oculomotor nerve palsy, visual loss, facial nerve palsy, facial neuralgia, directly related to meningioma and suggesting meningioma growth with increase of meningioma compression on neurological structures despite no increasing size on MRIs.
* Patients must have failed surgery, and not amenable to a new curative intended surgery
* Patients must have failed radiotherapy and/or radiosurgery
* Prior chemotherapy is allowed, if progression under the cytotoxic agent is clearly documented. An interval of 4 weeks after the last administration of the cytotoxic agent is warranted. Number of prior chemotherapies is not limited.
* Patients who have given their written consent
* Patients affiliated to a social insurance regime
* Adequate bone marrow function as shown by: Absolute Neutrophil Count ≥ 1.5 x 109/L,
* Platelets ≥ 100 x 109/L, Hb \>9 g/dL
* Adequate liver function as shown by; serum bilirubin ≤ 1.5 x Upper Limit of Normal; International Normalized Ratio \< 1.3; alanine aminotransferase and aspartate aminotransferase ≤ 2.5 x Upper Limit of Normal - Adequate renal function: serum creatinine ≤ 1.5 x Upper Limit of Normal - Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L and fasting triglycerides ≤ 2.5 x Upper Limit of Normal. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after dyslipidemia treatment initiation.

Exclusion Criteria:

* Patients with symptomatic lithiasis
* Contra indication to octreotide and everolimus
* Women of child-bearing age who are using no effective means of contraception
* Pregnant or breast-feeding women or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes
* Patients receiving other investigational agents or who received an investigative drug or therapy within the last 30 days.
* Known intolerance or hypersensitivity to octreotide, everolimus or other rapamycin (sirolimus, temsirolimus)
* Uncontrolled diabetes mellitus defined by HbA1c\>8.5%
* Patients who have any severe and/or uncontrolled medical condition:

unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to inclusion, serious uncontrolled cardiac arrhythmia, active or uncontrolled severe infection, cirrhosis, chronic active hepatitis or chronic persistent hepatitis, severely impaired lung function (spirometry and Diffusing Capacity of the lung for carbon monoxide 50% or less of normal and O2 saturation 88% or less at rest on room air), active, bleeding diathesis

* Patients receiving chronic treatment with immunosuppressive agent
* Patients with a known history of HIV seropositivity
* Patients who have a history of another primary malignancy ≤ 3 years, with the exceptions of non-melanoma skin cancer, and carcinoma in situ of uterine cervix.
* Females patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control.

Primary outcomes:
measure: The Progression Free Survival rate
timeFrame: 36 months
Secondary outcomes:
Other outcomes:
Locations:
city: Marseille
country: France
facility: Assistance Publique Hôpitaux Marseille
Study officials:
References: