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

Primary Purpose

Glioma, Other Solid Tumours

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

LAM561

About this trial

This is an interventional treatment trial for Glioma focused on measuring Glioma, Solid Tumours, LAM561

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Vall D'Hebron Institute of Oncology
Instituto Oncológico IMQ, Clínica IMQ Zorrotzaurre
Onkologikoa
Sir Bobby Robson Cancer Trials Research Centre, The Northern Centre for Cancer Care, Freeman Hospital
The Royal Marsden Hospital Drug Development Unit

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Arm Label

Dose Cohort 1

Dose Cohort 2

Dose Cohort 3

LAM561 Dose Cohort 4

LAM561 Dose Cohort 5

LAM561Dose Cohort 6

LAM561 Dose Cohort 7

LAM561 Dose Expansion cohort. Glioma

LAM561 Dose Expansion cohort. Non-glioma

Arm Description

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.

Intervention: LAM561. 500 mg twice daily

Intervention: LAM561. 1g twice daily

Intervention: LAM561. 2g twice daily

Intervention: LAM561. 4g twice daily

Intervention: LAM561. 4g three times daily

Intervention: LAM561. 8g twice daily

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

Concentration of micro RNA in blood

Blood samples for future analysis of micro RNA

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).

Clinical disease progression

Full Information

NCT ID

NCT01792310

First Posted

December 24, 2012

Last Updated

February 17, 2023

Sponsor

Laminar Pharmaceuticals

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT01792310

Brief Title

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

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Completed

Study Start Date

May 2013 (undefined)

Primary Completion Date

September 2016 (Actual)

Study Completion Date

September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Laminar Pharmaceuticals

Collaborators

4. Oversight

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioma, Other Solid Tumours

Keywords

Glioma, Solid Tumours, LAM561

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

54 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose Cohort 1

Arm Type

Experimental

Arm Description

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.

Arm Title

Dose Cohort 2

Arm Type

Experimental

Arm Description

Intervention: LAM561. 500 mg twice daily

Arm Title

Dose Cohort 3

Arm Type

Experimental

Arm Description

Intervention: LAM561. 1g twice daily

Arm Title

LAM561 Dose Cohort 4

Arm Type

Experimental

Arm Description

Intervention: LAM561. 2g twice daily

Arm Title

LAM561 Dose Cohort 5

Arm Type

Experimental

Arm Description

Intervention: LAM561. 4g twice daily

Arm Title

LAM561Dose Cohort 6

Arm Type

Experimental

Arm Description

Intervention: LAM561. 4g three times daily

Arm Title

LAM561 Dose Cohort 7

Arm Type

Experimental

Arm Description

Intervention: LAM561. 8g twice daily

Arm Title

LAM561 Dose Expansion cohort. Glioma

Arm Type

Experimental

Arm Description

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

Arm Title

LAM561 Dose Expansion cohort. Non-glioma

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

LAM561

Intervention Description

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 Outcome Measure Information:

Title

Number of patients with adverse events

Description

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

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

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

Time Frame

21 days

Title

Concentration of biomarkers in blood or tumour tissue

Description

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

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)

Title

Concentration of micro RNA in blood

Description

Blood samples for future analysis of micro RNA

Time Frame

Title

Radiological disease progression

Description

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)

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials: