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The proposed Phase IIB/III randomized, double-blind, placebo-controlled trial in subjects with newly diagnosed primary glioblastoma multiforme (ndGBM) aims to compare the efficacy and safety of LAM561 versus placebo, given with standard of care (SoC) therapy of radiation therapy plus temozolomide (TMZ), followed by an adjuvant treatment of 6 month period of TMZ and then LAM561 or placebo in monotherapy.
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
Eligible Ages | 18 Years - 75 Years |
Gender | All |
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT04250922 |
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 2/Phase 3 |
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
Laminar Pharmaceuticals |
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
N/A |
Principal Investigator Affiliation | N/A |
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Industry, Other |
Overall Status | Recruiting |
Countries | France, Israel, Italy, Spain, United Kingdom |
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Primary Glioblastoma, Glioblastoma Multiforme |
This is a randomized, double-blind, placebo-controlled, 2 parallel arms (1:1 ratio), adjuvant trial to assess the efficacy of LAM561 versus placebo in patients with newly diagnosed, IDH1 wildtype, GBM. In all arms, patients will receive the SoC and will be randomized to receive either placebo or LAM561 dose. The study is planned to enrol 140 patients. The primary endpoints of the study are PFS (for CMA) and OS (for FMA) as assessed after observing at least 66 PFS events and at least 90 OS events, respectively. It is expected that the analysis for PFS will be performed 1-2 years earlier than the analysis for OS. An IDMC (Independent Data Monitoring Committee) meeting took place to assess the trial's futility and safety data from the start of the trial until September 2023. The IDMC had open access to the data without blinding; after analysis IDMC concluded that there were no concerns that would necessitate stopping the study for ethical reasons or safety issues that could adversely affect patients due to taking the medication, so the study is continuing as normal with no changes. After 45 events for PFS are observed, a formal interim analysis will be performed and the data reviewed by an Independent Data Monitoring Committee (IDMC) or may be activated by the IDMC 12 months after the inclusion of the last patient if follow up is sufficient to identify an overall PFS or OS significant deviation from the literature. After reviewing the interim results, the iDMC will make recommendations regarding: the sample size and the continuation of the trial overall. Further, the sample size and events will be re-estimated to ensure that the statistical power is maintained given the estimated treatment effect at interim analysis. The events/sample size increase will be based on the considerations of the success probability. For that purpose, based on the conditional power, the interim results will be classified into the following zones: favourable, unfavourable or promising. If the interim results fall in the promising zone, then it is planned to increase the total number of events both for PFS and OS by up to 50%, with up to 99 events for PFS and up to 135 events for OS. The total sample size will also be increased to up to 210 patients to ensure the desired number of events within a realistic time. If the interim results are favourable or unfavourable, the study size will remain as initially planned with 66 events for PFS and 90 for OS, collected from 140 patients. The IDMC committee experts met in February 2024 after 45 PFS events occurred in the trial. Unblinded medical and clinical statistical data from 103 patients were evaluated to assess the efficacy
Placebo Comparator: Arm A: SoC + placebo for LAM561
Chemoradiation Phase: all subjects undergo focal RT, with a treatment given 5 days per week over ~6 weeks (no more than 7 weeks). TMZ will be administered at 75 mg/m2 orally, once daily, continuously throughout the RT for a maximum of 49 days. Subjects in Arm A will receive placebo every day from Day 1 of week 3 to the end of this Phase. The start of the first cycle during the Maintenance (Adjuvant) Phase will be scheduled ~28 days (and never more than 42 days) after the last day of chemoradiation. During the Maintenance Phase, subjects will receive oral TMZ 150-200 mg/m2 once daily on Days 1-5 of each 28-day cycle for 6 cycles. Subjects in Arm A will receive placebo every day during the first 3 weeks of each 28-day cycle and until progression. Patients will continue with Placebo after cycle 6 of the monotherapy phase until end of study. Adjuvant treatment will be discontinued upon determination of tumour progression, unacceptable toxicity or refusal to continue study treatment.
Experimental: Arm B: SoC + 12 g/day of LAM561
Chemoradiation Phase: all subjects undergo focal RT, with a treatment given 5 days per week over ~6 weeks (no more than 7 weeks). TMZ will be administered at 75 mg/m2 orally, once daily, continuously throughout the RT for a maximum of 49 days. Subjects in Arm B will receive LAM561 every day from Day 1 of week 3 to the end of this Phase. The start of the first cycle during the Maintenance Phase will be scheduled ~28 days (and never more than 42 days) after the last day of chemoradiation. During the Maintenance Phase, subjects will receive oral TMZ 150-200 mg/m2 once daily on Days 1-5 of each 28-day cycle for 6 cycles. Subjects in Arm B will receive LAM561 during the Maintenance Phase. Patients will continue to be administered with LAM561 after cycle 6 of the monotherapy phase until end of study. Adjuvant treatment will be discontinued upon determination of tumour progression, unacceptable toxicity or refusal to continue study treatment.
Drug: - LAM561
Subjects in Arm B will receive orally LAM561 during the Chemoradiation Phase. Subjects in Arm B will receive LAM561 orally during the Maintenance (Adjuvant) Phase. Patients will continue to be administered with LAM561/Placebo after cycle 6 of the monotherapy phase until end of study. Adjuvant treatment will be discontinued upon determination of tumour progression as defined by RANO criteria, unacceptable toxicity, or refusal to continue study treatment.
Drug: - TMZ
TMZ will be administered at 75 mg/m2, orally, once daily, continuously from Day 1 of radiotherapy to the last day of radiation for a maximum of 49 days. During the Maintenance (Adjuvant) Phase, all subjects will receive oral TMZ 150 - 200 mg/m2 once daily on Days 1 - 5 of each 28-day cycle for 6 cycles.
Radiation: - RT
During the Chemoradiation Phase, all subjects will undergo focal RT, with one treatment given daily 5 days per week over approximately 6 weeks (and no more than 7 weeks).
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Active, not recruiting
Address
Institut Cancerologie de L'Ouest (ICO)
Angers, ,
Status
Recruiting
Address
Centre Eugène Marquis (CEM)
Rennes, ,
Status
Recruiting
Address
Gustave Roussy University Hospital
Rennes, ,
Status
Recruiting
Address
Institut universitaire du cancer
Toulouse, ,
Status
Completed
Address
Reaserch Fund of the Hadassah Medical Organization
Jerusalem, ,
Status
Not yet recruiting
Address
Istituto Oncologico Veneto IRCCS
Padova, Veneto, 35131
Status
Recruiting
Address
Istituto Nazionale Neurologico Carlo Besta
Milan, ,
Status
Recruiting
Address
Istituto Nazionale Tumori "Regina Elena"
Roma, ,
Status
Recruiting
Address
University of Turin
Turin, ,
Status
Recruiting
Address
Hospital Universitario Reina Sofía
Córdoba, Andalucía,
Status
Recruiting
Address
Hospital Universitario Virgen del Rocío
Sevilla, Andalucía,
Status
Recruiting
Address
Hospital Universitari i Politécnic La Fe.
Valencia, Comunidad Valenciana, 46026
Status
Recruiting
Address
Hospital Clinic
Barcelona, ,
Status
Recruiting
Address
Hospital del Mar
Barcelona, ,
Status
Recruiting
Address
Hospital Vall d'Hebron
Barcelona, ,
Status
Recruiting
Address
Hospital Clínico San Carlos
Madrid, ,
Status
Recruiting
Address
Hospital Universitario 12 De Octubre
Madrid, ,
Status
Recruiting
Address
Hospital Parc Tauli
Sabadell, ,
Status
Recruiting
Address
Freeman Hospital's Northern Centre of Cancer Care
Newcastle, Newcastle Upon Tyne, NE7 7DN
Status
Recruiting
Address
University Hospitals Birmingham NHS Foundation Trust - New Queen Elizabeth Hospital
Birmingham, ,
Status
Recruiting
Address
Cambridge university hospital
Cambridge, ,
Status
Recruiting
Address
The Royal Marsden Hospital
London, ,