NCT01792310

Brief Summary

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

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
54

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started May 2013

Typical duration for phase_1

Geographic Reach
2 countries

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 24, 2012

Completed
2 months until next milestone

First Posted

Study publicly available on registry

February 15, 2013

Completed
3 months until next milestone

Study Start

First participant enrolled

May 1, 2013

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2016

Completed
Last Updated

February 21, 2023

Status Verified

February 1, 2023

Enrollment Period

3.3 years

First QC Date

December 24, 2012

Last Update Submit

February 17, 2023

Conditions

GliomaOther Solid Tumours

Keywords

GliomaSolid TumoursLAM561

Outcome Measures

Primary Outcomes (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

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

Secondary Outcomes (5)

  • Concentration of LAM561 in blood measured by LC-MS/MS

    21 days

  • 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)

  • 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)

  • 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)

  • Clinical disease progression

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

Study Arms (9)

Dose Cohort 1

EXPERIMENTAL

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.

Drug: LAM561

Dose Cohort 2

EXPERIMENTAL

Intervention: LAM561. 500 mg twice daily

Drug: LAM561

Dose Cohort 3

EXPERIMENTAL

Intervention: LAM561. 1g twice daily

Drug: LAM561

LAM561 Dose Cohort 4

EXPERIMENTAL

Intervention: LAM561. 2g twice daily

Drug: LAM561

LAM561 Dose Cohort 5

EXPERIMENTAL

Intervention: LAM561. 4g twice daily

Drug: LAM561

LAM561Dose Cohort 6

EXPERIMENTAL

Intervention: LAM561. 4g three times daily

Drug: LAM561

LAM561 Dose Cohort 7

EXPERIMENTAL

Intervention: LAM561. 8g twice daily

Drug: LAM561

LAM561 Dose Expansion cohort. Glioma

EXPERIMENTAL

Intervention: LAM561 at the MTD: 4g three times daily. Up to 10 patients with malignant glioma.

Drug: LAM561

LAM561 Dose Expansion cohort. Non-glioma

EXPERIMENTAL

Intervention: LAM561 at the MTD: 4g three times daily. Up to 10 patients with other advanced solid tumours that are suitable for biopsy.

Drug: LAM561

Interventions

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.

Dose Cohort 1Dose Cohort 2Dose Cohort 3LAM561 Dose Cohort 4LAM561 Dose Cohort 5LAM561 Dose Cohort 7LAM561 Dose Expansion cohort. GliomaLAM561 Dose Expansion cohort. Non-gliomaLAM561Dose Cohort 6

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Vall D'Hebron Institute of Oncology

Barcelona, Spain

Location

Instituto Oncológico IMQ, Clínica IMQ Zorrotzaurre

Bilbao, Spain

Location

Onkologikoa

San Sebastián, Spain

Location

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

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

Location

The Royal Marsden Hospital Drug Development Unit

Sutton, Surrey, SM25PT, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 37488446DERIVED

MeSH Terms

Conditions

Glioma

Condition Hierarchy (Ancestors)

Neoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Study Officials

  • Professor Johann de Bono, MB ChB FRCP MSc PhD

    The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey, United Kingdom SM2 5NG

    STUDY CHAIR

  • Prof. Ruth Plummer, BMBCh, MRCP, Cert Me

    Northern Institute for Cancer Research, Newcastle

    PRINCIPAL INVESTIGATOR

  • Dr Jordi Rodon

    Vall d'Hebron Institute of Oncology

    PRINCIPAL INVESTIGATOR

  • Dr Juanita Lopez

    The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey, United Kingdom SM2 5NG

    PRINCIPAL INVESTIGATOR

  • Dr Ricardo Fernandez Rodriguez

    Instituto Oncológico IMQ, Clínica IMQ Zorrotzaurre. Bilbao

    PRINCIPAL INVESTIGATOR

  • Dr Ander Urruticoechea Ribate

    Onkologikoa, San Sebastián.

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 24, 2012

First Posted

February 15, 2013

Study Start

May 1, 2013

Primary Completion

September 1, 2016

Study Completion

September 1, 2016

Last Updated

February 21, 2023

Record last verified: 2023-02

Locations

GB(2)ES(3)