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

Laminar Pharma

Status and phase: Completed; Phase 2; Phase 1

Conditions: Glioma; Other Solid Tumours

Treatments: Drug: LAM561

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01792310

MIN-001-1203

EudraCT 2012-001527-13 (Registry Identifier)

Details and patient eligibility

About

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

Full 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

Enrollment: 54 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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54 participants in 9 patient groups

Dose Cohort 1

Experimental group

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.

Treatment:

Drug: LAM561

Dose Cohort 2

Experimental group

Description:

Intervention: LAM561. 500 mg twice daily

Treatment:

Drug: LAM561

Dose Cohort 3

Experimental group

Description:

Intervention: LAM561. 1g twice daily

Treatment:

Drug: LAM561

LAM561 Dose Cohort 4

Experimental group

Description:

Intervention: LAM561. 2g twice daily

Treatment:

Drug: LAM561

LAM561 Dose Cohort 5

Experimental group

Description:

Intervention: LAM561. 4g twice daily

Treatment:

Drug: LAM561

LAM561Dose Cohort 6

Experimental group

Description:

Intervention: LAM561. 4g three times daily

Treatment:

Drug: LAM561

LAM561 Dose Cohort 7

Experimental group

Description:

Intervention: LAM561. 8g twice daily

Treatment:

Drug: LAM561

LAM561 Dose Expansion cohort. Glioma

Experimental group

Description:

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

Treatment:

Drug: LAM561

LAM561 Dose Expansion cohort. Non-glioma

Experimental group

Description:

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

Treatment:

Drug: LAM561