MeningiomaPhase 1ALTREMNCT03631953
Combination of Alpelisib and Trametinib in Progressive Refractory Meningiomas
A Phase 1 study testing Trametinib, Alpelisib and Blood sample in people with Meningioma, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Meningioma
- What is being tested?
- Trametinib, Alpelisib and Blood sample
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteFrance
- Study dates
- 30 Sep 2019to 30 Dec 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- No receiving other investigational agents
- Written informed consent
- Adequate bone marrow function
- Adequate liver function as shown by
- Adequate renal function
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Combination of Alpelisib and Trametinib in Progressive Refractory Meningiomas: Phase 1 Study
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.
Read more
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).
- Conditions
- Meningioma
- Being tested
- Trametinib, Alpelisib, Blood sample, MRI
- Medical subject headings
- Meningioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrametinibDrug
Trametinib administered at a fixed dose (1.5 mg daily)
AlpelisibDrug
A panel of 3 doses of ALPELISIB could be tested
Blood sampleBiological
Therapeutic biomarkers
MRIDevice
A MRI with contrast will be performed before treatment start. Assessment of tumor growth.
| Study group | Role | What they receive |
|---|---|---|
| Alpelisib in combination with Trametinib administered | Experimental | A panel of 3 doses of Alpelisib could be tested in combination with fixed dose of Trametinib (1.5 mg every day). Receives: Drug: Trametinib; Drug: Alpelisib; Biological: Blood sample; Device: MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2018
- Study start30 Sep 2019
- Primary completion12 Oct 2026
- Study completion30 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MeningiomaStudies of the same condition, open and under way.
- More trials run by Assistance Publique Hopitaux De MarseilleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean-Oliver ARNAUD, Director, Study director, Assistance Publique Hôpitaux de Marseille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03631953
- Sponsor's protocol ID
- 2018-05
- Other IDs
- RCAPHM18_0015
- Acronym
- ALTREM
- Status last verified
- Oct 2026
- First submitted
- 13 Aug 2018
- Last updated
- 2 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination of Alpelisib and Trametinib in Progressive Refractory Meningiomas: Phase 1 Study
- ClinicalTrials.gov ID
- NCT03631953
- Acronym / sponsor ID
- ALTREM / 2018-05
- Conditions
- Meningioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- 30 Sep 2019 (actual)
- Primary completion
- 12 Oct 2026 (actual)
- Study completion
- 30 Dec 2028 (estimated)
- First posted
- 15 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alpelisib in combination with Trametinib administered | Experimental | Drug: Trametinib, Drug: Alpelisib, Biological: Blood sample, Device: MRIA panel of 3 doses of Alpelisib could be tested in combination with fixed dose of Trametinib (1.5 mg every day). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrametinibTrametinib administered at a fixed dose (1.5 mg daily) | Drug | Alpelisib in combination with Trametinib administered |
| AlpelisibA panel of 3 doses of ALPELISIB could be tested | Drug | Alpelisib in combination with Trametinib administered |
| Blood sampleTherapeutic biomarkers | Biological | Alpelisib in combination with Trametinib administered |
| MRIA MRI with contrast will be performed before treatment start. Assessment of tumor growth. | Device | Alpelisib in combination with Trametinib administered |
Primary outcome
Dose Limiting Toxicity (DLT) rate of combination Alpelisib and Trametinib
Time frame: 36 months
Evaluate adverse events graded (toxicity) according to National Cancer Institute's Common Toxicity Criteria (version 4.0).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Oliver ARNAUD, Director study director
Assistance Publique Hôpitaux de Marseille
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Trametinib, Alpelisib and Blood sample in people with Meningioma, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (DLT) rate of combination Alpelisib and Trametinib (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.