GlioblastomaPhase 1MARELLE01NCT03631836
Phase I Study of Monoclonal Antibondy (GS) 5745, an Matix Metalloproteinase 9 (MMP9) Mab Inhibitor, in Combination With Bevacizumab in Patients With Recurrent Glioblastoma
A Phase 1 study testing Monoclonal antibody, Bevacizumab and Blood sample in people with Glioblastoma, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
Trial summary
Despite surgery and first-line standard of care which consist of radiotherapy with concomitant and adjuvant temozolomide, all patients with glioblastoma (GB) will experience relapse. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Monoclonal antibody, Bevacizumab and Blood sample
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jan 2019to 1 Jan 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 confirmed diagnosis of isocitrate dehydrogenase (IDH) wild-type glioblastoma
- First or second recurrence after standard treatment with combined chemo-irradiation
- Patients must have measurable tumour disease as defined by Response assessment in neuro-oncology (RANO) criteria within 2 weeks before the first drug administration
- Stable or decreasing dose of corticosteroids within 5 days prior first administration
- Karnofsky Performance Status superior at 60%
- Negative serum or urine pregnancy test done inferior or egal at 7 days prior to registration, for women of childbearing potential only
- Provide informed written consent
Who cannot join
- Major surgery (including craniotomy) within 4 weeks prior to the first day of study drug administration
- Chemotherapy within 4 weeks prior to the first day of study drug administration
- Radiotherapy within 3 months prior the diagnosis of progression.
- Prior treatment with bevacizumab or other vascular endothelial growth factor (VEGF) receptor targeted agent
- Evidence of Central Nervous System (CNS) haemorrhage on the baseline MRI.
- Other conditions reported to exclude bevacizumab administration
Show all 11Show fewer
- Men or women of childbearing potential who are unwilling to employ adequate contraception during this study
- Concomitant serious immunocompromised status
- Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
- Other active malignancy within 5 years of registration. Exceptions: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
Trial locations and contacts
1 site in 1 country.
France1 site
Assistance Publique des Hôpitaux de Marseille
Marseille, 13354
Olivier CHINOT, PU-PH, 491385500 ext. +33, olivier.chinot@ap-hm.fr
Olivier CHINOT, PU-PH
About this study
Despite surgery and first-line standard of care which consist of radiotherapy with concomitant and adjuvant temozolomide, all patients with glioblastoma (GB) will experience relapse. At the time of recurrence, therapeutic options include surgery or reirradiation in selected cases, while in other cases, bevacizumab, approved by Food and Drug Administration (FDA) but not European Medicines Agency (EMA), is the preferred option worldwide. Primary and acquired resistance to bevacizumab has been explored without definitive finding.
Biomarkers able to predict response to antiangiogenic agents and particularly to bevacizumab are an unmet medical need. We have showed that a low Matrix metallopeptidase 9 (MMP9) or a high Matrix metallopeptidase 2 (MMP2) baseline plasma levels were associated with a high response rate and a prolonged Progression-free survival (PFS) and overall survival (OS) in recurrent GB patients treated with bevacizumab but not with cytotoxic chemotherapy. We also observed that MMP9 plasma level decreased during bevacizumab treatment and tend to increase at progression. Finally, in a retrospective analysis performed in the Avaglio trial (a randomized phase III trial that tested bevacizumab versus placebo in addition to standard of care in patients with newly diagnosed glioblastoma), a low plasma level of MMP9 at baseline predicted consistently PFS and OS gain associated to bevacizumab.
Read more
These results are consistent with the role of MMP9 in vasculogenesis, since MMP9 contribute to the recruitment of circulating endothelial and myeloid precursors, an alternative vascularization process which is in part independent of the vascular endothelial growth factor (VEGF) pathway.
Monoclonal Antibody (GS) 5745 is specifically directed against MMP9. First in human phase I study has been completed. Development is ongoing.
Our results strongly support a role for MMP9 in the primary or acquired resistance to bevacizumab. Therefore, we hypothesize that the Monoclonal Antibody GS5745 may overcome resistance to bevacizumab through a specific inhibition of MMP9. While a preclinical program is initiated in our lab, the proposed phase I study is the first step to analyze the tolerance, determine the recommended dose of the combination and explore the impact of GS5745 on MMP9 plasma levels and multimodal imaging in patients with recurrent glioblastoma.
Objective:
Determine the safety profile and tolerability of GS5745 given in combination with a fixed dose of bevacizumab in patients with recurrent GB in terms of Dose-Limiting Toxicities.
Multicenter, open label, dose-finding study of GS5745 in combination with bevacizumab administered at a fixed dose; both drugs will be administered once every two weeks for a total treatment duration of a maximum of 12 months.
Before initiation of each new dose level, a meeting between the sponsor, the coordinator, the investigators and an independent external expert will take place to decide jointly the next dose.
- Conditions
- Glioblastoma
- Being tested
- Monoclonal antibody, Bevacizumab, Blood sample, Dynamic Contrast Enhanced magnetic resonance imaging (DCE-MRI)
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Monoclonal antibodyDrug
3 doses of Monoclonal antibody could be tested
BevacizumabDrug
fixed dose of bevacizumab (10 mg/ kg every two weeks)
Blood sampleBiological
Evaluate the biomarkers plasma levels during administration of drug
Dynamic Contrast Enhanced magnetic resonance imaging (DCE-MRI)Device
Assess antiangiogenic effects by DCE-MRI
| Study group | Role | What they receive |
|---|---|---|
| Combinaton monoclonal therapeutic antibody and bevacizumab | Experimental | Determine the safety profile and tolerability of monoclonal therapeutic antibody given in combination with a fixed dose of bevacizumab in patients with recurrent glioblastoma in terms of Dose-Limiting Toxicities Receives: Drug: Monoclonal antibody; Drug: Bevacizumab; Biological: Blood sample; Device: Dynamic Contrast Enhanced magnetic resonance imaging (DCE-MRI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the Dose Limiting Toxicity (DLT)
Toxicities are to be graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Any grade 4 event and selected grade 3 events of any duration.
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 start1 Jan 2019 (estimated)
- Primary completion1 Jan 2022 (estimated)
- Study completion1 Jan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies 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
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean-Olivier ARNAUD, Director, Study director, Assistance Publique des Hôpitaux de Marseille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03631836
- Sponsor's protocol ID
- 2017-65
- Acronym
- MARELLE01
- Status last verified
- Aug 2018
- First submitted
- 13 Aug 2018
- Last updated
- 17 Aug 2018
- 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 17 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Monoclonal Antibondy (GS) 5745, an Matix Metalloproteinase 9 (MMP9) Mab Inhibitor, in Combination With Bevacizumab in Patients With Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT03631836
- Acronym / sponsor ID
- MARELLE01 / 2017-65
- Conditions
- Glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- 1 Jan 2019 (estimated)
- Primary completion
- 1 Jan 2022 (estimated)
- Study completion
- 1 Jan 2022 (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.
Despite surgery and first-line standard of care which consist of radiotherapy with concomitant and adjuvant temozolomide, all patients with glioblastoma (GB) will experience relapse. At the time of recurrence, therapeutic options include surgery or reirradiation in selected cases, while in other cases, bevacizumab, approved by Food and Drug Administration (FDA) but not European Medicines Agency (EMA), is the preferred option worldwide. Primary and acquired resistance to bevacizumab has been explored without definitive finding.
Biomarkers able to predict response to antiangiogenic agents and particularly to bevacizumab are an unmet medical need. We have showed that a low Matrix metallopeptidase 9 (MMP9) or a high Matrix metallopeptidase 2 (MMP2) baseline plasma levels were associated with a high response rate and a prolonged Progression-free survival (PFS) and overall survival (OS) in recurrent GB patients treated with bevacizumab but not with cytotoxic chemotherapy. We also observed that MMP9 plasma level decreased during bevacizumab treatment and tend to increase at progression. Finally, in a retrospective analysis performed in the Avaglio trial (a randomized phase III trial that tested bevacizumab versus placebo in addition to standard of care in patients with newly diagnosed glioblastoma), a low plasma level of MMP9 at baseline predicted consistently PFS and OS gain associated to bevacizumab.
These results are consistent with the role of MMP9 in vasculogenesis, since MMP9 contribute to the recruitment of circulating endothelial and myeloid precursors, an alternative vascularization process which is in part independent of the vascular endothelial growth factor (VEGF) pathway.
Monoclonal Antibody (GS) 5745 is specifically directed against MMP9. First in human phase I study has been completed. Development is ongoing.
Our results strongly support a role for MMP9 in the primary or acquired resistance to bevacizumab. Therefore, we hypothesize that the Monoclonal Antibody GS5745 may overcome resistance to bevacizumab through a specific inhibition of MMP9. While a preclinical program is initiated in our lab, the proposed phase I study is the first step to analyze the tolerance, determine the recommended dose of the combination and explore the impact of GS5745 on MMP9 plasma levels and multimodal imaging in patients with recurrent glioblastoma.
Objective:
Determine the safety profile and tolerability of GS5745 given in combination with a fixed dose of bevacizumab in patients with recurrent GB in terms of Dose-Limiting Toxicities.
Multicenter, open label, dose-finding study of GS5745 in combination with bevacizumab administered at a fixed dose; both drugs will be administered once every two weeks for a total treatment duration of a maximum of 12 months.
Before initiation of each new dose level, a meeting between the sponsor, the coordinator, the investigators and an independent external expert will take place to decide jointly the next dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combinaton monoclonal therapeutic antibody and bevacizumab | Experimental | Drug: Monoclonal antibody, Drug: Bevacizumab, Biological: Blood sample, Device: Dynamic Contrast Enhanced magnetic resonance imaging (DCE-MRI)Determine the safety profile and tolerability of monoclonal therapeutic antibody given in combination with a fixed dose of bevacizumab in patients with recurrent glioblastoma in terms of Dose-Limiting Toxicities |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histologically confirmed diagnosis of isocitrate dehydrogenase (IDH) wild-type glioblastoma
- First or second recurrence after standard treatment with combined chemo-irradiation
- Patients must have measurable tumour disease as defined by Response assessment in neuro-oncology (RANO) criteria within 2 weeks before the first drug administration
- Stable or decreasing dose of corticosteroids within 5 days prior first administration
- Karnofsky Performance Status superior at 60%
Key exclusion criteria (11 listed)
- Major surgery (including craniotomy) within 4 weeks prior to the first day of study drug administration
- Chemotherapy within 4 weeks prior to the first day of study drug administration
- Radiotherapy within 3 months prior the diagnosis of progression.
- Prior treatment with bevacizumab or other vascular endothelial growth factor (VEGF) receptor targeted agent
- Evidence of Central Nervous System (CNS) haemorrhage on the baseline MRI.
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 |
|---|---|---|
| Monoclonal antibody3 doses of Monoclonal antibody could be tested | Drug | Combinaton monoclonal therapeutic antibody and bevacizumab |
| Bevacizumabfixed dose of bevacizumab (10 mg/ kg every two weeks) | Drug | Combinaton monoclonal therapeutic antibody and bevacizumab |
| Blood sampleEvaluate the biomarkers plasma levels during administration of drug | Biological | Combinaton monoclonal therapeutic antibody and bevacizumab |
| Dynamic Contrast Enhanced magnetic resonance imaging (DCE-MRI)Assess antiangiogenic effects by DCE-MRI | Device | Combinaton monoclonal therapeutic antibody and bevacizumab |
Primary outcome
Determine the Dose Limiting Toxicity (DLT)
Time frame: 36 months
Toxicities are to be graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Any grade 4 event and selected grade 3 events of any duration.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2018.
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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-Olivier ARNAUD, Director study director
Assistance Publique des 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 Monoclonal antibody, Bevacizumab and Blood sample in people with Glioblastoma, 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 7 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: status not confirmed, as of the sponsor's last update on 17 Aug 2018. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Olivier CHINOT, PU-PH (491385500 ext. +33, olivier.chinot@ap-hm.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the Dose Limiting Toxicity (DLT) (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 17 Aug 2018.