Overview

This trial has been completed.

Conditions glioma, other solid tumours
Treatment 2-hydroxyoleic acid (2-ohoa/2ohoa)
Phase phase 1/phase 2
Sponsor Lipopharma Therapeutics SL
Collaborator Specialized Medical Services (SMS)-Oncology BV
Start date May 2013
End date September 2016
Trial size 54 participants
Trial identifier NCT01792310, EudraCT 2012-001527-13, MIN-001-1203

Summary

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(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.
2-hydroxyoleic acid (2-ohoa/2ohoa) Minerval®
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.
(Experimental)
Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 500 mg twice daily
2-hydroxyoleic acid (2-ohoa/2ohoa) Minerval®
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.
(Experimental)
Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 1g twice daily
2-hydroxyoleic acid (2-ohoa/2ohoa) Minerval®
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.
(Experimental)
Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 2g twice daily
2-hydroxyoleic acid (2-ohoa/2ohoa) Minerval®
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.
(Experimental)
Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 4g twice daily
2-hydroxyoleic acid (2-ohoa/2ohoa) Minerval®
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.
(Experimental)
Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 4g three times daily
2-hydroxyoleic acid (2-ohoa/2ohoa) Minerval®
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.
(Experimental)
Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 8g twice daily
2-hydroxyoleic acid (2-ohoa/2ohoa) Minerval®
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.
(Experimental)
Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA) at the MTD: 4g three times daily. Up to 10 patients with malignant glioma.
2-hydroxyoleic acid (2-ohoa/2ohoa) Minerval®
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.
(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.
2-hydroxyoleic acid (2-ohoa/2ohoa) Minerval®
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.

Primary Outcomes

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

Secondary Outcomes

Measure
Concentration of 2-OHOA in blood measured by LC-MS/MS
time frame: 21 days
Concentration of biomarkers in blood or tumour tissue
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)
Concentration of micro RNA in blood
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)
Radiological disease progression
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)
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

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Phase 1/2A Dose Escalation Study of 2-hydroxyoleic Acid (2-OHOA; Minerval®) in Adult Patients With Advanced Solid Tumours Including Malignant Glioma
Principal investigator Prof. Ruth Plummer, BMBCh, MRCP, Cert Me
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 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
Trial information was received from ClinicalTrials.gov and was last updated in December 2016.
Information provided to ClinicalTrials.gov by Lipopharma Therapeutics SL.