LAM561 With RT and TMZ for Adults With Glioblastoma

NCT04250922 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MIN-003-1806
• Study Type: interventional
• Target: 144
• Locations: 5 countries
• Sites: 22

Brief Summary

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.

Conditions

Primary Glioblastoma; Glioblastoma Multiforme

Keywords

malignant

Outcome Measures

Primary Outcomes (2)

• To evaluate the efficacy of LAM561 in combination with the standard of care (SoC) treatment of radiotherapy (RT) and TMZ.

  To evaluate the efficacy of LAM561 in combination with the standard of care (SoC) treatment of radiotherapy (RT) and TMZ, as assessed by \- Progression Free Survival (PFS) using the Response Assessment in Neuro-Oncology (RANO) criteria

  Assessed after observing at least 66 PFS events

• To evaluate the efficacy of LAM561 in combination with the standard of care (SoC) treatment of radiotherapy (RT) and TMZ.

  To evaluate the efficacy of LAM561 in combination with the standard of care (SoC) treatment of radiotherapy (RT) and TMZ, as assessed by \- Overall Survival (OS)

  Assessed after observing at least 90 OS events

Secondary Outcomes (8)

• To evaluate measures of clinical response

  Baseline and Post-baseline: day 1 of each odd cycle of maintenance/monotherapy phase and at progression

• To evaluate additional measures of efficacy

  Baseline and Post-baseline: day 1 of each odd cycle of maintenance/monotherapy phase and at progression

• To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) parameters

  At week 3 and 5 (day in both cases) of chemo-radiotherapy phase and at day 1 and 15 of cycle 1 of the maintenance phase

• To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) parameters

  At week 3 and 5 (day in both cases) of chemo-radiotherapy phase and at day 1 and 15 of cycle 1 of the maintenance phase

• To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) parameters

  At week 3 and 5 (day in both cases) of chemo-radiotherapy phase and at day 1 and 15 of cycle 1 of the maintenance phase

Study Arms (2)

Arm A: SoC + placebo for LAM561

PLACEBO COMPARATOR

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.

Drug: TMZ; Radiation: RT

Arm B: SoC + 12 g/day of LAM561

EXPERIMENTAL

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; Drug: TMZ; Radiation: RT

Interventions

LAM561 DRUG

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.

Arm B: SoC + 12 g/day of LAM561

TMZ DRUG

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.

Arm A: SoC + placebo for LAM561; Arm B: SoC + 12 g/day of LAM561

RT RADIATION

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).

Arm A: SoC + placebo for LAM561; Arm B: SoC + 12 g/day of LAM561

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent, signed and dated
• Subjects who are able to understand and follow instructions during the trial
• Age ≥18 and ≤75
• Subjects with newly histologically confirmed intracranial malignant glioma (glioblastoma WHO Grade IV) that is IDH1 wildtype (local assessment) and who are scheduled to receive chemo-radiotherapy with temozolomide
• Ability to swallow and retain oral medication
• Centrally obtained MGMT promoter methylation status
• Subjects who underwent total or partial / incomplete resection and with the appropriate quantity of tumour tissue releasable for eligibility
• Karnofsky Performance Score (KPS) \> 50 %
• Women must be:
• Either of NOT childbearing potential: postmenopausal (≥ 60 years of age, or \< 60 years of age and amenorrhoea for 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression with follicle-stimulating hormone (FSH) above 40 U/L and oestradiol below 30 ng/L, or if taking tamoxifen or toremifene, and age \< 60 years, then FSH and oestradiol in the postmenopausal range), permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy), or otherwise incapable of pregnancy
• Or of childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; male partner sterilization (the vasectomized partner should be the sole partner for that subject).
• A man who is sexually active and has not had a vasectomy must agree to use a barrier method of birth control e.g., either condom or partner with occlusive cap (diaphragm or cervical/vault caps).
• Adequate bone marrow function including: Absolute neutrophil count (ANC) ≥1,500/mm\^3 or ≥1.5 x 10\^9/L; Platelets ≥ 100,000/mm3 or ≥100 x10\^9/L; Haemoglobin ≥ 9 g/dL (may have been transfused).
• Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal range (ULN), an aspartate aminotransferase (AST), level ≤ 2.5 × ULN, and an alanine aminotransferase (ALT) level ≤ 2.5 × ULN or, for subjects with documented metastatic disease to the liver, AST and ALT levels ≤ 5 × ULN. Subjects with documented Gilbert disease are allowed if total bilirubin ≤ 3 x ULN
• Adequate renal function defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula

You may not qualify if:

• Known hypersensitivity to any component of the investigational product.
• Any other investigational drug within the preceding 30 days. Prior, concomitant, or planned concomitant treatment with anti-neoplastic aim including (but not limited) to NovoTumor Treatment Fields (Novo TTF), bevacizumab, intratumoural or intracavitary anti-neoplastic therapy (e.g Gliadel wafers), or other experimental therapeutics intended to treat the tumour.
• Subjects who underwent "only biopsy" resection
• Anticancer therapy within 4 weeks of study entry (6 weeks for mitomycin and nitrosoureas)
• Other major surgery within the preceding 30 days
• Allergy, hypersensitivity or other intolerability to temozolomide and its excipients, patients with hypersensitivity to dacarbazine and patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
• Unable to undergo MRI
• Presenting with diffuse midline gliomas or multifocal GBM (distant from the flare or contralateral) or rapid progression between early post-surgery MRI and pre-radiotherapy MRI
• Uncontrolled or significant cardiovascular disease
• A history of uncontrolled hyperlipidaemia and/or the need for concurrent lipid lowering therapy
• Need for warfarin, phenytoin or sulphonylureas (glibenclamide, glimepiride, glipizide, glyburide or nateglanide)
• Past medical history of uncontrolled clinically significant active or chronic gastrointestinal disorders (for example, Crohn's disease, celiac disease, untreated stomach ulcers, etc) and gastro-inflammatory pathologies
• Uncontrolled diabetes mellitus, with glycated haemoglobin (HbA1c) levels at the screening visit of ≥7.5%
• Cardiac disease, defined specifically as either
• Mean resting corrected QT interval (QTc) \> 470 msec (for women) and \> 450 ms (for men) obtained from 3 consecutive ECGs

Sponsors & Collaborators

• Laminar Pharmaceuticals: lead
• Laboratory Corporation of America: collaborator
• Northern Institute for Cancer Research, Newcastle: collaborator
• Theradis pharma: collaborator
• LIPODOM THERAPEUTICS: collaborator

Study Sites (22)

Institut Cancerologie de L'Ouest (ICO)

Angers, France

Location

Centre Eugène Marquis (CEM)

Rennes, France

Location

Gustave Roussy University Hospital

Rennes, France

Location

Institut universitaire du cancer

Toulouse, France

Location

Reaserch Fund of the Hadassah Medical Organization

Jerusalem, Israel

Location

Istituto Oncologico Veneto IRCCS

Padua, Veneto, 35131, Italy

Location

Istituto Nazionale Neurologico Carlo Besta

Milan, Italy

Location

Istituto Nazionale Tumori "Regina Elena"

Roma, Italy

Location

University of Turin

Turin, Italy

Location

Hospital Universitario Reina Sofía

Córdoba, Andalusia, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Andalusia, Spain

Location

Hospital Clinic

Barcelona, Barcelona, Spain

Location

Hospital Vall d'Hebron

Barcelona, Barcelona, Spain

Location

Hospital Clínico San Carlos

Madrid, Madrid, Spain

Location

Hospital Universitari i Politécnic La Fe.

Valencia, Valencia, 46026, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Universitario 12 De Octubre

Madrid, Spain

Location

Hospital Parc Tauli

Sabadell, Spain

Location

Freeman Hospital's Northern Centre of Cancer Care

Newcastle, Newcastle Upon Tyne, NE7 7DN, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust - New Queen Elizabeth Hospital

Birmingham, United Kingdom

Location

Cambridge university hospital

Cambridge, United Kingdom

Location

The Royal Marsden Hospital

London, United Kingdom

Location

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: At the Screening Visit, the IRT will assign a unique number to the subject. The site will use the IRT to receive drug kit numbers and a unique randomization number. Subjects will be randomized to Arm A or B in a 1:1 ratio. Drug kit numbers and treatment content will be assigned according to a list generated before the start of the study. At interim, the IRT vendor will transfer the list of attribution to the iSCs. After the final lock, the list of attribution will be transmitted to the company involved in analysis. The IRT vendor will be in charge of the stock management/logistics in each site and shipments. Upon receipt of study drug, the study site will acknowledge receipt in the IRT system. The investigators, the study site personnel and subject will remain blinded to throughout the course of the study. The IRT will provide access to for a subject in case of medical emergency. If sponsor/clinical team should break the blind, the reason will be documented on the eCRF.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a randomized, double-blind, placebo-controlled, 2 parallel arms (1:1), adjuvant trial to assess the efficacy of LAM561 vs placebo in patients with ndGBM. The 2 arms are: Arm A: SoC + placebo for LAM561; Arm B: SoC + 12g/day of LAM561 Treatment consists of 3 phases: 1. Chemoradiotherapy (6 to 7 weeks) * RT in daily fractions of 2Gy, 5 days per week (60Gy) * TMZ 75mg/m2 daily (maximum of 49 days) * Placebo or LAM561 for 4 weeks (from week 3 to week 6, both inclusive) -Washout period (4 weeks) 2. Maintenance (4-week cycles, maximum of 6 cycles) * Placebo/LAM561 daily in the first 3 weeks of each cycle, followed by 7 days washout * TMZ 150-200mg/m2 daily in the first 5 days of each cycle 3. Monotherapy: 4-week cycles until disease progression, unacceptable toxicity or lack of clinical benefit Placebo/LAM561 daily in the first 3 weeks of each cycle followed by 7 days washout

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: January 31, 2020
• Study Start: December 1, 2019
• Primary Completion: January 15, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: November 20, 2025

Record last verified: 2025-11

Locations

FR (4); IL (1); ES (9); GB (4); IT (4)