Combination of Alpelisib and Trametinib in Progressive Refractory Meningiomas (ALTREM)
Primary Purpose
Meningioma
Status
Unknown status
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Trametinib
Alpelisib
Blood sample
MRI
Sponsored by
About this trial
This is an interventional treatment trial for Meningioma
Eligibility Criteria
Inclusion Criteria:
- Histologically proven meningioma grade I, II and III
- Progression is defined as growing meningiomas on 2 different Magnetic Resonance Imaging (MRI) 3 to 6 months apart
- Patients must have failed surgery, and not amenable to a new curative intended surgery
- Patients must have failed radiotherapy and/or radiosurgery
- Patients who have given their written consent
- No contra indication to Alpelisib and Trametinib
- No receiving other investigational agents
- Written informed consent
- Adequate bone marrow function
- Adequate liver function as shown by
- Adequate renal function
Exclusion Criteria:
- Contra indication to Alpelisib and Trametinib
- Women of child-bearing age who are using no effective means of contraception
- Pregnant or breast-feeding women
- Patients receiving other investigational agents
- Known intolerance or hypersensitivity to Alpelisib and Trametinib
- Uncontrolled diabetes mellitus
- Patients who have any severe and uncontrolled medical condition
- Patients receiving chronic treatment with immunosuppressives
- Patients with a known history of HIV seropositivity
- Patients who have a history of another primary malignancy less than or equal to 3 years, with
- the exceptions of non-melanoma skin cancer, and carcinoma in situ of uterine cervix
Sites / Locations
- Assistance Publique Hôpitaux de MarseilleRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Alpelisib in combination with Trametinib administered
Arm Description
A panel of 3 doses of Alpelisib could be tested in combination with fixed dose of Trametinib (1.5 mg every day).
Outcomes
Primary Outcome Measures
Dose Limiting Toxicity (DLT) rate of combination Alpelisib and Trametinib
Evaluate adverse events graded (toxicity) according to National Cancer Institute's Common Toxicity Criteria (version 4.0).
Secondary Outcome Measures
Full Information
NCT ID
NCT03631953
First Posted
August 13, 2018
Last Updated
April 29, 2020
Sponsor
Assistance Publique Hopitaux De Marseille
1. Study Identification
Unique Protocol Identification Number
NCT03631953
Brief Title
Combination of Alpelisib and Trametinib in Progressive Refractory Meningiomas
Acronym
ALTREM
Official Title
Combination of Alpelisib and Trametinib in Progressive Refractory Meningiomas: Phase 1 Study
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Unknown status
Study Start Date
September 30, 2019 (Actual)
Primary Completion Date
September 1, 2022 (Anticipated)
Study Completion Date
September 1, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique Hopitaux De Marseille
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Aggressive growing meningiomas resistant to multiple surgeries and radiotherapy constitute an unmet pharmaceutical need in neurooncology, leading to a fatal issue within a few months. Grade II-III meningiomas progression-free survival (PFS) 6 is at 10-15%. Median PFS grade III meningioma is approximate 3 years.
Alpelisib is a well-tolerated Phosphoinositide 3-kinase α (Pi3Kα) specific inhibitor. However, phosphatidylinositol-3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) inhibition does not induce apoptosis in vitro and induces an antiproliferative effect without any radiologic response in most treated patients.
Trametinib, a mekinist (MEK) inhibitor is currently used in combined treatment for recurrent melanomas in clinical practice with a good clinical tolerance at 1-2 mg daily. In vitro, on meningioma primary cell culture, Trametinib induces cell apoptosis via caspase activity.
These results strongly suggest the relevance to combine Alpelisib and Trametinib in aggressive and recurrent meningiomas.
Alpelisib and Trametinib combination has not been studied to date, despite each drugs have been separately studied in phase 3.
Multicenter, open label, dose-finding phase I study of Alpelisib in combination with Trametinib administered at a fixed dose (1.5 mg daily), both drugs will be administered daily. Starting dose of Alpelisib will be 160mg/day and will be increased to 200mg/day or decreased to 120mg/day depending of grade 3-4 adverse events occurrence, to determine maximal tolerated dose (MTD) and recommended dose.
Primary Objective is to determine the safety profile and tolerability of Alpelisib and Trametinib given in combination in patients with aggressive and refractory meningiomas in terms of Dose-Limiting Toxicities (DLT, assessed during cycle 1).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Meningioma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Alpelisib in combination with Trametinib administered
Arm Type
Experimental
Arm Description
A panel of 3 doses of Alpelisib could be tested in combination with fixed dose of Trametinib (1.5 mg every day).
Intervention Type
Drug
Intervention Name(s)
Trametinib
Intervention Description
Trametinib administered at a fixed dose (1.5 mg daily)
Intervention Type
Drug
Intervention Name(s)
Alpelisib
Intervention Description
A panel of 3 doses of ALPELISIB could be tested
Intervention Type
Biological
Intervention Name(s)
Blood sample
Intervention Description
Therapeutic biomarkers
Intervention Type
Device
Intervention Name(s)
MRI
Intervention Description
A MRI with contrast will be performed before treatment start. Assessment of tumor growth.
Primary Outcome Measure Information:
Title
Dose Limiting Toxicity (DLT) rate of combination Alpelisib and Trametinib
Description
Evaluate adverse events graded (toxicity) according to National Cancer Institute's Common Toxicity Criteria (version 4.0).
Time Frame
36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically proven meningioma grade I, II and III
Progression is defined as growing meningiomas on 2 different Magnetic Resonance Imaging (MRI) 3 to 6 months apart
Patients must have failed surgery, and not amenable to a new curative intended surgery
Patients must have failed radiotherapy and/or radiosurgery
Patients who have given their written consent
No contra indication to Alpelisib and Trametinib
No receiving other investigational agents
Written informed consent
Adequate bone marrow function
Adequate liver function as shown by
Adequate renal function
Exclusion Criteria:
Contra indication to Alpelisib and Trametinib
Women of child-bearing age who are using no effective means of contraception
Pregnant or breast-feeding women
Patients receiving other investigational agents
Known intolerance or hypersensitivity to Alpelisib and Trametinib
Uncontrolled diabetes mellitus
Patients who have any severe and uncontrolled medical condition
Patients receiving chronic treatment with immunosuppressives
Patients with a known history of HIV seropositivity
Patients who have a history of another primary malignancy less than or equal to 3 years, with
the exceptions of non-melanoma skin cancer, and carcinoma in situ of uterine cervix
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Thomas GRAILLON, PH
Phone
491385545
Ext
+33
Email
thomas.graillon@ap-hm.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Olivier CHINOT, PU-PH
Phone
491385545
Ext
+33
Email
olivier.chinot@ap-hm.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Oliver ARNAUD, Director
Organizational Affiliation
Assistance Publique Hôpitaux de Marseille
Official's Role
Study Director
Facility Information:
Facility Name
Assistance Publique Hôpitaux de Marseille
City
Marseille
ZIP/Postal Code
13354
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas GRAILLON, PH
Phone
491385545
Ext
+33
Email
thomas.graillon@ap-hm.fr
First Name & Middle Initial & Last Name & Degree
Olivier CHINOT, PU-PH
Phone
491385545
Ext
+33
Email
olivier.chinot@ap-hm.fr
First Name & Middle Initial & Last Name & Degree
Thomas GRAILLON, PH
12. IPD Sharing Statement
Learn more about this trial
Combination of Alpelisib and Trametinib in Progressive Refractory Meningiomas
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