A Phase 1/2A Study of LAM561 in Adult Patients With Advanced Solid Tumours
- Registration Number
- NCT01792310
- Lead Sponsor
- Laminar Pharmaceuticals
- Brief Summary
This is a phase 1/2A, open label, non-randomized study in patients with advanced solid tumours including malignant glioma
- Detailed Description
This is an open label, non-randomized study in patients with advanced solid tumours including malignant glioma. The study will be performed in two phases - a dose escalation phase following a standard "3+3" design to establish dose-limiting toxicity (DLT) and a safe dose of LAM561 followed by two expanded safety cohorts (approximately 10 of whom have malignant glioma and approximately 10 of whom have other advanced solid tumours that are suitable for biopsy) treated at the maximum tolerated dose (MTD). If the MTD is well tolerated in the expanded safety cohorts, that dose becomes the recommended phase 2 dose (RP2D). During each dose cohort, at least one week must elapse between the first and subsequent patients receiving treatment with LAM561. Patients may receive palliative localized radiotherapy, if needed (however, this lesion cannot be a target lesion for evaluation of the treatment response).
Safety, pharmacokinetics (PK), pharmacodynamics and efficacy will be evaluated during the study at pre-defined timepoints
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 54
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LAM561 Dose Cohort 7 LAM561 Intervention: LAM561. 8g twice daily Dose Cohort 1 LAM561 Intervention: LAM561. 7 dose cohorts of up to 6 patients have been performed in the dose escalation phase. The starting dose cohort received 250 mg twice daily. Dose Cohort 2 LAM561 Intervention: LAM561. 500 mg twice daily Dose Cohort 3 LAM561 Intervention: LAM561. 1g twice daily LAM561 Dose Cohort 4 LAM561 Intervention: LAM561. 2g twice daily LAM561 Dose Cohort 5 LAM561 Intervention: LAM561. 4g twice daily LAM561Dose Cohort 6 LAM561 Intervention: LAM561. 4g three times daily LAM561 Dose Expansion cohort. Glioma LAM561 Intervention: LAM561 at the MTD: 4g three times daily. Up to 10 patients with malignant glioma. LAM561 Dose Expansion cohort. Non-glioma LAM561 Intervention: LAM561 at the MTD: 4g three times daily. Up to 10 patients with other advanced solid tumours that are suitable for biopsy.
- Primary Outcome Measures
Name Time Method Number of patients with adverse events From the first dose of study drug until 30 days after the last dose of study drug All adverse events will be recorded including clinically significant physical examinations and vital signs, laboratory safety tests and 12-lead electrocardiograms
- Secondary Outcome Measures
Name Time Method Concentration of LAM561 in blood measured by LC-MS/MS 21 days Full profiles on Day 1 and Day 21 (dose escalation phase only), trough measurements on Day 8, 15 and 21
Concentration of micro RNA in blood First 22 days then every 9 cycles until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion) Blood samples for future analysis of micro RNA
Radiological disease progression Every 6 weeks until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion) Measurement by CT or MRI scan. Changes scored according to Response Assessment in Neuro-oncology (RANO) criteria (for glioma patients) or Response evaluation criteria in solid tumours (RECIST v1.1) (for other solid tumour patients).
Concentration of biomarkers in blood or tumour tissue First 22 days then every 9 cycles until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion) Effect on glial fibrillary acidic protein in glioma patients and effect on sphingomyelin and dihydrofolate reductase in patients with other solid tumours
Clinical disease progression until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion
Trial Locations
- Locations (5)
Vall D'Hebron Institute of Oncology
🇪🇸Barcelona, Spain
Instituto Oncológico IMQ, ClÃnica IMQ Zorrotzaurre
🇪🇸Bilbao, Spain
Onkologikoa
🇪🇸San Sebastián, Spain
The Royal Marsden Hospital Drug Development Unit
🇬🇧Sutton, Surrey, United Kingdom
Sir Bobby Robson Cancer Trials Research Centre, The Northern Centre for Cancer Care, Freeman Hospital
🇬🇧Newcastle, Newcastle Upon Tyne, United Kingdom