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Completed

NCT Number: NCT01792310

A Phase 1/2A Study of LAM561 in Adult Patients With Advanced Solid Tumours

This is a phase 1/2A, open label, non-randomized study in patients with advanced solid tumours including malignant glioma

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Key information

Conditions

Glioma Neoplasms Neoplasms by Histologic Type Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neuroectodermal Tumors Other Solid Tumours

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Vall D'Hebron Institute of Oncology, Barcelona, Spain

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

LAM561

Drug

Patients will receive treatment cycles of 21 days, until any criterion for discontinuation (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion) is met.

Patients are expected to receive between one and 6 cycles of treatment. The treatment period may be extended if clinical benefit is shown.

In the event of significant GI toxicity, the treatment schedule may be modified from continuous dosing to an intermittent regime In the case of toxicity, the dose of LAM561 may be reduced or delayed by up to 14 days at the discretion of the Investigator. A maximum of two dose reductions will be permitted per patient. Treatment "holidays" of no more than 14 days are also permitted for reasons other than toxicity. Intra-patient dose escalation may be permitted in certain specific circumstances.

Primary outcomes

  1. Number of patients with adverse events

    Time frame: 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 outcomes

  1. Concentration of LAM561 in blood measured by LC-MS/MS

    Time frame: 21 days

    Full profiles on Day 1 and Day 21 (dose escalation phase only), trough measurements on Day 8, 15 and 21

  2. Concentration of biomarkers in blood or tumour tissue

    Time frame: 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

  3. Concentration of micro RNA in blood

    Time frame: 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

  4. Radiological disease progression

    Time frame: 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).

  5. Clinical disease progression

    Time frame: until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion

Sponsors and collaborators

Lead sponsor

Laminar Pharmaceuticals

Industry

Collaborators

  • Instituto Oncológico IMQ, Clínica IMQ Zorrotzaurre. Bilbao
  • Northern Institute for Cancer Research, Newcastle
  • Onkologikoa, San Sebastián.
  • Royal Marsden NHS Foundation Trust
  • Specialized Medical Services (SMS)-Oncology BV
  • Vall d'Hebron Institute of Oncology

Registry information

Official study title

A Phase 1/2A Dose Escalation Study of LAM561 in Adult Patients With Advanced Solid Tumours Including Malignant Glioma

Important dates

Study start
2013
Primary completion
2016
Study completion
2016
First posted
Feb 15, 2013
Registry last updated
Feb 21, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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