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GliomaPhase 1/2NCT01792310

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

A Phase 1/2 study testing LAM561 in people with Glioma and Other Solid Tumours, run by Laminar Pharmaceuticals at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioma, Other Solid Tumours
What is being tested?
LAM561
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
5 sitesin 2 countries
Study dates
May 2013to Sep 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 9Show fewer
  • 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

Trial locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

Spain3 sites

  • Vall D'Hebron Institute of Oncology

    Barcelona

  • Instituto Oncológico IMQ, Clínica IMQ Zorrotzaurre

    Bilbao

  • Onkologikoa

    San Sebastián

Other trials in Spain

United Kingdom2 sites

  • Sir Bobby Robson Cancer Trials Research Centre, The Northern Centre for Cancer Care, Freeman Hospital

    Newcastle, Newcastle Upon Tyne, NE7 7DN

  • The Royal Marsden Hospital Drug Development Unit

    Sutton, Surrey, SM25PT

Other trials in United Kingdom

About this study

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

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

Read the 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

Being tested
LAM561
Keywords
Glioma, Solid Tumours, LAM561
Medical subject headings
Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LAM561Drug

    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.

Study groups in NCT01792310
Study groupRoleWhat they receive
Dose Cohort 1ExperimentalIntervention: 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.
Receives: Drug: LAM561
Dose Cohort 2ExperimentalIntervention: LAM561. 500 mg twice daily
Receives: Drug: LAM561
Dose Cohort 3ExperimentalIntervention: LAM561. 1g twice daily
Receives: Drug: LAM561
LAM561 Dose Cohort 4ExperimentalIntervention: LAM561. 2g twice daily
Receives: Drug: LAM561
LAM561 Dose Cohort 5ExperimentalIntervention: LAM561. 4g twice daily
Receives: Drug: LAM561
LAM561Dose Cohort 6ExperimentalIntervention: LAM561. 4g three times daily
Receives: Drug: LAM561
LAM561 Dose Cohort 7ExperimentalIntervention: LAM561. 8g twice daily
Receives: Drug: LAM561
LAM561 Dose Expansion cohort. GliomaExperimentalIntervention: LAM561 at the MTD: 4g three times daily. Up to 10 patients with malignant glioma.
Receives: Drug: LAM561
LAM561 Dose Expansion cohort. Non-gliomaExperimentalIntervention: LAM561 at the MTD: 4g three times daily. Up to 10 patients with other advanced solid tumours that are suitable for biopsy.
Receives: Drug: LAM561

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of patients with adverse events

    All adverse events will be recorded including clinically significant physical examinations and vital signs, laboratory safety tests and 12-lead electrocardiograms

    Measured: From the first dose of study drug until 30 days after the last dose of study drug

Secondary outcomes (5)

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

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

    Measured: 21 days

  2. Concentration of biomarkers in blood or tumour tissue

    Effect on glial fibrillary acidic protein in glioma patients and effect on sphingomyelin and dihydrofolate reductase in patients with other solid tumours

    Measured: 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)

  3. Concentration of micro RNA in blood

    Blood samples for future analysis of micro RNA

    Measured: 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)

  4. Radiological disease progression

    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).

    Measured: Every 6 weeks until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion)

  5. Clinical disease progression

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2013 (estimated)
  2. Study startMay 2013
  3. Primary completionSep 2016
  4. Study completionSep 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01792310
Sponsor's protocol ID
MIN-001-1203
Other IDs
EudraCT 2012-001527-13
Status last verified
Feb 2023
First submitted
24 Dec 2012
Last updated
21 Feb 2023
Results posted
No
Data monitoring committee
No

Publications

  • Lopez J, Lai-Kwon J, Molife R, Welsh L, Tunariu N, Roda D, Fernandez-Garcia P, Llado V, McNicholl AG, Rossello CA, Taylor RJ, Azaro A, Rodon J, Sludden J, Veal GJ, Plummer R, Urruticoechea A, Lahuerta A, Mujika K, Escriba PV. A Phase 1/2A trial of idroxioleic acid: first-in-class sphingolipid regulator and glioma cell autophagy inducer with antitumor activity in refractory glioma. Br J Cancer. 2023 Sep;129(5):811-818. doi: 10.1038/s41416-023-02356-1. Epub 2023 Jul 24.

    PubMed 37488446

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LAM561 in people with Glioma and Other Solid Tumours, run by Laminar Pharmaceuticals at 5 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01792310, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2023.

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