Trial | NCT01792310  Report issue

Title

A Phase 1/2A Study of Minerval in Adult Patients With Advanced Solid Tumours
A Phase 1/2A Dose Escalation Study of 2-hydroxyoleic Acid (2-OHOA; Minerval®) in Adult Patients With Advanced Solid Tumours Including Malignant Glioma

  • Phase

    Phase 1/Phase 2

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    54
This is a phase 1/2A, open label, non-randomized study in patients with advanced solid tumours including malignant glioma
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 2-OHOA 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 2-OHOA. 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
Study Started
May 31
2013
Primary Completion
Sep 30
2016
Study Completion
Sep 30
2016
Last Update
Dec 06
2016
Estimate

Drug 2-hydroxyoleic acid (2-OHOA/2OHOA)

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 2-OHOA 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.

  • Other names: Minerval®

Dose Cohort 1 Experimental

Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 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.

Dose Cohort 2 Experimental

Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 500 mg twice daily

Dose Cohort 3 Experimental

Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 1g twice daily

2-OHOA Dose Cohort 4 Experimental

Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 2g twice daily

2-OHOA Dose Cohort 5 Experimental

Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 4g twice daily

2-OHOA Dose Cohort 6 Experimental

Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 4g three times daily

2-OHOA Dose Cohort 7 Experimental

Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 8g twice daily

2-OHOA Dose Expansion cohort. Glioma Experimental

Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA) at the MTD: 4g three times daily. Up to 10 patients with malignant glioma.

2-OHOA Dose Expansion cohort. Non-glioma Experimental

Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA) at the MTD: 4g three times daily. Up to 10 patients with other advanced solid tumours that are suitable for biopsy.

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
No Results Posted