Clinical trial NCT01792310: A Phase 1/2A Study of LAM561 in Adult Patients With Advanced Solid Tumours
Official title: A Phase 1/2A Dose Escalation Study of LAM561 in Adult Patients With Advanced Solid Tumours Including Malignant Glioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Glioma
Other Solid Tumours
Keywords: Glioma
Solid Tumours
LAM561
Lead sponsor: Laminar Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Specialized Medical Services (SMS)-Oncology BV
name: Royal Marsden NHS Foundation Trust
name: Northern Institute for Cancer Research, Newcastle
name: Vall d'Hebron Institute of Oncology
name: Instituto Oncológico IMQ, Clínica IMQ Zorrotzaurre. Bilbao
name: Onkologikoa, San Sebastián.
First posted: 2013-02-15
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria

* Males or females providing written, informed consent
* Histologically- or cytologically-confirmed advanced solid malignancy that is refractory to standard-of-care treatment, or for which there is no standard therapy. If this is glioma:Grade III / Grade IV malignant glioma recurring or progressing after first or second line standard-of-care treatment and true progressive disease, confirmed according to the RANO criteria 4.
* Life-expectancy of at least 12 weeks
* Eastern cooperative oncology group (ECOG) performance status of 0-2
* Safety laboratory tests and ECGs within specified limits.
* Using adequate contraception, where applicable
* Presence of lesions suitable for biopsy (mandatory for non-glioma patients enrolled in the expanded safety cohort and highly desirable for non-glioma patients enrolled in the dose escalation phase)

Exclusion Criteria

* Anti cancer therapy within 4 weeks (6 weeks for mitomycin and nitrosureas and 2 weeks for palliative radiotherapy)
* NCI Common terminology criteria for adverse events (CTCAE) \>Grade 1 toxicities from prior chemotherapy or radiotherapy that could impact on safety outcome assessment
* Recent \>Grade 1 intracranial or intratumoural haemorrhage either by CT or MRI scan. Patients with resolving haemorrhage changes, punctuate haemorrhage or haemosiderin may enter the study
* Significant or uncontrolled cardiovascular disease, unstable angina or myocardial infarction within the preceding 6 months
* Known impairment of GI function that could alter the absorption of study drug
* History of uncontrolled hyperlipidemia and/or the need for concurrent lipid lowering therapy
* Concurrent severe and/or uncontrolled other medical disease that could compromise participation in the study
* Taking warfarin, phenytoin or sulphonylureas (glibenclamide, glimepiride, glipizide, glyburide or nateglanide)
* Pregnant or breast feeding Other protocol specific criteria may apply

Primary outcomes:
measure: Number of patients with adverse events
timeFrame: From the first dose of study drug until 30 days after the last dose of study drug
Secondary outcomes:
measure: Concentration of LAM561 in blood measured by LC-MS/MS
timeFrame: 21 days
measure: Concentration of biomarkers in blood or tumour tissue
timeFrame: 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)
measure: Concentration of micro RNA in blood
timeFrame: 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)
measure: Radiological disease progression
timeFrame: Every 6 weeks until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion)
measure: Clinical disease progression
timeFrame: until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Vall D'Hebron Institute of Oncology
city: Bilbao
country: Spain
facility: Instituto Oncológico IMQ, Clínica IMQ Zorrotzaurre
city: San Sebastián
country: Spain
facility: Onkologikoa
city: Newcastle
country: United Kingdom
facility: Sir Bobby Robson Cancer Trials Research Centre, The Northern Centre for Cancer Care, Freeman Hospital
state: Newcastle Upon Tyne
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital Drug Development Unit
state: Surrey
Study officials:
affiliation: The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey, United Kingdom SM2 5NG
name: Professor Johann de Bono, MB ChB FRCP MSc PhD
role: STUDY_CHAIR
affiliation: Northern Institute for Cancer Research, Newcastle
name: Prof. Ruth Plummer, BMBCh, MRCP, Cert Me
role: PRINCIPAL_INVESTIGATOR
affiliation: Vall d'Hebron Institute of Oncology
name: Dr Jordi Rodon
role: PRINCIPAL_INVESTIGATOR
affiliation: The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey, United Kingdom SM2 5NG
name: Dr Juanita Lopez
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Oncológico IMQ, Clínica IMQ Zorrotzaurre. Bilbao
name: Dr Ricardo Fernandez Rodriguez
role: PRINCIPAL_INVESTIGATOR
affiliation: Onkologikoa, San Sebastián.
name: Dr Ander Urruticoechea Ribate
role: PRINCIPAL_INVESTIGATOR
References: