Glioblastoma (GBM)Phase 1NCT03867123
A Study to Evaluate the Safety of LAM561 Added to Standard of Care in Newly-diagnosed Glioblastoma Patients
A Phase 1 study testing LAM561, RT and TMZ in people with Glioblastoma (GBM), run by Laminar Pharmaceuticals at 3 sites in Spain.
Trial summary
The purpose of this study is to determine the safety and tolerability of LAM561 added to first-line treatment for subjects with newly diagnosed glioblastoma (GBM), and to determine the highest safe dose of LAM561 administered orally when added to the concurrent phase of treatment with temozolomide (TMZ) and radiation… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma (GBM)
- What is being tested?
- LAM561, RT and TMZ
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 3 sitesSpain
- Study dates
- 4 Dec 2018to 1 Jul 2020
- 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
- Glioblastoma (GBM) according to 2016 World Health Organization (WHO) Classification.
- Must have had a partial or complete surgical resection of the Grade 4 astrocytic tumor.
- Subjects in Arm 1 must have had no previous treatment except surgery (ie, no previous RT, local CT, or systemic therapy). Subjects must meet certain other eligibility requirements.
- Subjects in Arm 2 must have completed a standard first line regimen of concurrent TMZ and RT for newly diagnosed GBM patients, followed by a rest phase, and have not had any other previous CT except surgery (including any other regimens of RT and local or systemic CT). Progression and/or pseudoprogression should have been ruled out before starting Arm 2 as per usual clinical practice, with correct laboratory results (absolute neutrophile count ≥1.5 x 109/L, platelet count ≥ 100 x 109/L, non-haematological toxicity grade ≤ 2) at screening. Subjects must meet certain other eligibility requirements.
- Subjects must be able to undergo serial MRIs (computerized tomography may not be a substitute for magnetic resonance imaging [MRI]).
- Male or female ≥ 18 years old.
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- Must have a Karnofsky performance status of ≥ 70% and the ability to swallow oral medication.
- Must have no other diagnosis of cancer malignancy (except surgically excised nonmelanoma skin cancer or carcinoma in situ of the cervix, or treated early stage prostate cancer, or a malignancy diagnosed ≥ 5 years previously with no current evidence of disease and no therapy within two years prior to enrolment on this study).
- Must be capable of understanding and complying with the protocol requirements.
- Contraception: All female patients will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrhea, in the appropriate age group and without other known or suspected cause), or have been sterilized surgically. Female patients of childbearing potential must agree to use two forms of highly effective contraception methods (a primary and a secondary method) during the study and for a period of 6 months following the last administration of the study drug. Male patients and their female partners, who are of childbearing potential and are not practicing total abstinence, must agree to use two forms of highly effective contraception methods (a primary and a secondary method) during the study and for a period of 6 months following the last administration of the study drug These contraception methods include oral, transdermal, systemic or implant contraception birth control, intra-uterine devices (IUD), abstinence and double barrier method such as diaphragm with spermicidal gel or other recommended double barrier methods screening.
- Written informed consent form signed before any study test or procedure.
Who cannot join
- Subject has received prior systemic CT or RT (Arm 1) or prior systemic CT other than TMZ (Arm 2), biologic agents, or any other type of investigational agent for the treatment of brain tumors.
- Subjects who have progressed on TMZ are not eligible (pseudoprogression ruled out as per usual clinical practice).
- Subject has evidence of acute intracranial or intratumoral hemorrhage > Grade 1 by MRI. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin may enter the study.
- Subject has serious intercurrent illness such as: hypertension despite optimal treatment, or significant cardiac arrhythmias; or a recent history of serious disease such as symptomatic congestive heart failure, or abdominal fistula or gastrointestinal (GI) perforation within 6 months, prior to starting study treatment.
- Subject has had major surgery within 28 days prior to starting study treatment (except cancer resection surgery in arm 1), or had non water-tight dural closure during previous surgery, or has unhealed wounds from previous surgery.
- Subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding.
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- Subject is pregnant or breastfeeding.
- Subject is known to be positive for the human immunodeficiency virus (HIV) (a test for HIV at screening is not required).
- Subject has a previously-identified allergy or hypersensitivity to components of either the LAM561 or TMZ formulations.
- Subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
Institut Catala d'Oncologia, Hospital Germans Trias I Pujol
Badalona, Catalonia, 08916
Hospital Universitari de Girona Dr. Josep Trueta, Institut Català d'Oncologia
Girona, Catalonia, 17007
Hospital Duran i Reynals, Institut Català d'Oncologia
L'Hospitalet de Llobregat, Catalonia, 08908
About this study
Official title: A Phase 1B Study of the Safety of LAM561 Administered Orally in Combination With Temozolomide (TMZ) and Radiation Therapy or With TMZ Alone in the First Line Treatment of Subjects With Glioblastoma
The purpose of this study is to determine the safety and tolerability of LAM561 added to first-line treatment for subjects with newly diagnosed glioblastoma (GBM), and to determine the highest safe dose of LAM561 administered orally when added to the concurrent phase of treatment with temozolomide (TMZ) and radiation therapy (RT) or when added to the maintenance phase of treatment with TMZ (once TMZ 200 g/m2/day is started).
Read the detailed description
This is a Phase IB, open-label, dose-finding study. A de-escalation process has been selected for the study with a 3+3 design to establish the Maximum Tolerated Dose (MTD).
The first group of 3 subjects (within each arm), where all 3 subjects may be started at the same time, will receive LAM561 at the starting dose of 12 g/day (4 g tid). If 0-1 Dose-Limiting Toxicities (DLTs) in the first 3 patients, then a new cohort with 3 more patients is started at 12 g/day (4 g tid). If 2 or more patients out of 3 or 6 patients experience DLT(s) the dose is deescalated.
De-escalation doses are from 12 g/day (4 g tid) to 8 g/day (4 g bid) and from 8 g/day (4 g bid) to 4 g/day (4 g od). This procedure must be applied to the two arms of the study described below. Both arms will be independent, and will run in parallel, therefore none of the patients from Arm 1 may enter Arm 2.
- Conditions
- Glioblastoma (GBM)
- Being tested
- LAM561, RT, TMZ
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LAM561Drug
Arm 1: Daily for 6 weeks. Arm 2: daily, two 28-day cycles
RTRadiation
Also called radiotherapy
In Arm 1: Fractionated focal irradiation of 1.8-2 Gy/fraction/day, 5 days/week, 6 weeks. Total dose up to 60 Gy
TMZDrug
Also called temozolomide
Arm 1: 75 mg/m2/day, daily, 6 weeks Arm 2: 200 mg/m2/day, daily the first 5 days of two 28-day cycles (in case of toxicity, TMZ dose may be reduced to 150 mg/m2/day at Cycle 3 to allow for recovery)
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (chemoradiation phase) | Experimental | Radiotherapy (RT) + temozolomide (TMZ) + LAM561 (during Concurrent phase - duration 6 weeks)*:
LAM561 will be initiated at the start of the concurrent phase and will be administered on a continuous daily basis together with TMZ and RT for 6 weeks at the selected dose, either 12 g/day (4 g tid), 8 g/day (4 g bid) or 4 g/day (4 g od).
RT will be administered only during the concurrent phase, consisting of fractionated focal irradiation administered using 1.8- 2 Gy/fraction, daily for 5 days/week for 6 weeks, for a total dose of up to 60 Gy.
TMZ will be administered during the concurrent phase at a starting dose of 75 mg/m2/day given daily for 6 weeks.
* One extra week may be allowed. Receives: Drug: LAM561; Radiation: RT; Drug: TMZ |
| Arm 2 (maintenance phase) | Experimental | TMZ + LAM561 (during Maintenance phase with TMZ 200 mg/m2/day at Cycle 2 - duration 8 weeks):
LAM561 will be initiated on day 2 of Cycle 2 of the maintenance phase, when TMZ 200 mg/m2/day is given and administered on a continuous basis for two 28-day cycles. LAM561 will be administered at the selected dose, either 12 g/day (4 g tid), 8 g/day (4 g bid) or 4 g/day (4 g od).
TMZ will be administered at 200 mg/m2/day given daily the first 5 days for two 28-day cycles (if no toxicity is seen). In case of toxicity, TMZ dose may be reduced to 150 mg/m2/day at Cycle 3 to allow for recovery.
Both arms will be followed by a 4-week safety follow-up Receives: Drug: LAM561; Drug: TMZ |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of LAM561 in association with Standard of Care (Stupp Protocol)
Incidence of Treatment-Emergent Adverse Events.
Measured: 10 to 12 weeks
Maximum Tolerated dose (MTD)
MTD of LAM561 administered with Standard of Care
Measured: 10 to 12 months
Secondary outcomes (1)
Plasma concentration of temozolomide (TMZ).
To verify that the administration of LAM561 is not modifying the exposition of patients to TMZ.
Measured: First five days of cycle 2 of maintenance phase (each cycle is 4 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2019
- Study start4 Dec 2018
- Primary completion1 Jul 2020
- Study completion1 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma (GBM)Studies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laminar Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jordi Roma, MD, Study director, cro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03867123
- Sponsor's protocol ID
- MIN-002-1801
- Other IDs
- 2018-000317-21, 2018
- Status last verified
- Feb 2023
- First submitted
- 3 Jan 2019
- Last updated
- 21 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1B Study of the Safety of LAM561 Administered Orally in Combination With Temozolomide (TMZ) and Radiation Therapy or With TMZ Alone in the First Line Treatment of Subjects With Glioblastoma
- ClinicalTrials.gov ID
- NCT03867123
- Acronym / sponsor ID
- MIN-002-1801
- Conditions
- Glioblastoma (GBM)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Laminar PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 4 Dec 2018 (actual)
- Primary completion
- 1 Jul 2020 (actual)
- Study completion
- 1 Jul 2020 (actual)
- First posted
- 7 Mar 2019 (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.
The purpose of this study is to determine the safety and tolerability of LAM561 added to first-line treatment for subjects with newly diagnosed glioblastoma (GBM), and to determine the highest safe dose of LAM561 administered orally when added to the concurrent phase of treatment with temozolomide (TMZ) and radiation therapy (RT) or when added to the maintenance phase of treatment with TMZ (once TMZ 200 g/m2/day is started).
Detailed description
This is a Phase IB, open-label, dose-finding study. A de-escalation process has been selected for the study with a 3+3 design to establish the Maximum Tolerated Dose (MTD).
The first group of 3 subjects (within each arm), where all 3 subjects may be started at the same time, will receive LAM561 at the starting dose of 12 g/day (4 g tid). If 0-1 Dose-Limiting Toxicities (DLTs) in the first 3 patients, then a new cohort with 3 more patients is started at 12 g/day (4 g tid). If 2 or more patients out of 3 or 6 patients experience DLT(s) the dose is deescalated.
De-escalation doses are from 12 g/day (4 g tid) to 8 g/day (4 g bid) and from 8 g/day (4 g bid) to 4 g/day (4 g od). This procedure must be applied to the two arms of the study described below. Both arms will be independent, and will run in parallel, therefore none of the patients from Arm 1 may enter Arm 2.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (chemoradiation phase) | Experimental | Drug: LAM561, Radiation: RT, Drug: TMZRadiotherapy (RT) + temozolomide (TMZ) + LAM561 (during Concurrent phase - duration 6 weeks)*: LAM561 will be initiated at the start of the concurrent phase and will be administered on a continuous daily basis together with TMZ and RT for 6 weeks at the selected dose, either 12 g/day (4 g tid), 8 g/day (4 g bid) or 4 g/day (4 g od). RT will be administered only during the concurrent phase, consisting of fractionated focal irradiation administered using 1.8- 2 Gy/fraction, daily for 5 days/week for 6 weeks, for a total dose of up to 60 Gy. TMZ will be administered during the concurrent phase at a starting dose of 75 mg/m2/day given daily for 6 weeks. * One extra week may be allowed. |
| Arm 2 (maintenance phase) | Experimental | Drug: LAM561, Drug: TMZTMZ + LAM561 (during Maintenance phase with TMZ 200 mg/m2/day at Cycle 2 - duration 8 weeks): LAM561 will be initiated on day 2 of Cycle 2 of the maintenance phase, when TMZ 200 mg/m2/day is given and administered on a continuous basis for two 28-day cycles. LAM561 will be administered at the selected dose, either 12 g/day (4 g tid), 8 g/day (4 g bid) or 4 g/day (4 g od). TMZ will be administered at 200 mg/m2/day given daily the first 5 days for two 28-day cycles (if no toxicity is seen). In case of toxicity, TMZ dose may be reduced to 150 mg/m2/day at Cycle 3 to allow for recovery. Both arms will be followed by a 4-week safety follow-up |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Glioblastoma (GBM) according to 2016 World Health Organization (WHO) Classification.
- Must have had a partial or complete surgical resection of the Grade 4 astrocytic tumor.
- Subjects in Arm 1 must have had no previous treatment except surgery (ie, no previous RT, local CT, or systemic therapy). Subjects must meet certain other eligibility requirements.
- Subjects in Arm 2 must have completed a standard first line regimen of concurrent TMZ and RT for newly diagnosed GBM patients, followed by a rest phase, and have not had any other previous CT except surgery (including any other regimens of RT and local or systemic CT). Progression and/or pseudoprogression should have been ruled out before starting Arm 2 as per usual clinical practice, with correct laboratory results (absolute neutrophile count ≥1.5 x 109/L, platelet count ≥ 100 x 109/L, non-haematological toxicity grade ≤ 2) at screening. Subjects must meet certain other eligibility requirements.
- Subjects must be able to undergo serial MRIs (computerized tomography may not be a substitute for magnetic resonance imaging [MRI]).
Key exclusion criteria (10 listed)
- Subject has received prior systemic CT or RT (Arm 1) or prior systemic CT other than TMZ (Arm 2), biologic agents, or any other type of investigational agent for the treatment of brain tumors.
- Subjects who have progressed on TMZ are not eligible (pseudoprogression ruled out as per usual clinical practice).
- Subject has evidence of acute intracranial or intratumoral hemorrhage > Grade 1 by MRI. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin may enter the study.
- Subject has serious intercurrent illness such as: hypertension despite optimal treatment, or significant cardiac arrhythmias; or a recent history of serious disease such as symptomatic congestive heart failure, or abdominal fistula or gastrointestinal (GI) perforation within 6 months, prior to starting study treatment.
- Subject has had major surgery within 28 days prior to starting study treatment (except cancer resection surgery in arm 1), or had non water-tight dural closure during previous surgery, or has unhealed wounds from previous surgery.
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 |
|---|---|---|
| LAM561Arm 1: Daily for 6 weeks. Arm 2: daily, two 28-day cycles | Drug | Arm 1 (chemoradiation phase), Arm 2 (maintenance phase) |
| RTAlso: radiotherapyIn Arm 1: Fractionated focal irradiation of 1.8-2 Gy/fraction/day, 5 days/week, 6 weeks. Total dose up to 60 Gy | Radiation | Arm 1 (chemoradiation phase) |
| TMZAlso: temozolomideArm 1: 75 mg/m2/day, daily, 6 weeks Arm 2: 200 mg/m2/day, daily the first 5 days of two 28-day cycles (in case of toxicity, TMZ dose may be reduced to 150 mg/m2/day at Cycle 3 to allow for recovery) | Drug | Arm 1 (chemoradiation phase), Arm 2 (maintenance phase) |
Primary outcome
Safety and Tolerability of LAM561 in association with Standard of Care (Stupp Protocol)
Time frame: 10 to 12 weeks
Incidence of Treatment-Emergent Adverse Events.
Maximum Tolerated dose (MTD)
Time frame: 10 to 12 months
MTD of LAM561 administered with Standard of Care
1 secondary outcome
Plasma concentration of temozolomide (TMZ).
Time frame: First five days of cycle 2 of maintenance phase (each cycle is 4 weeks)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
- Individual participant dataSharing planned: Undecided
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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.
Jordi Roma, MD study director
cro
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LAM561, RT and TMZ in people with Glioblastoma (GBM), run by Laminar Pharmaceuticals at 3 sites in Spain.
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 10 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: finished, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety and Tolerability of LAM561 in association with Standard of Care (Stupp Protocol) (time frame: 10 to 12 weeks). The study lists 2 primary outcomes in all. 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 21 Feb 2023.