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Trial record 1 of 1 for:    min-001-1203
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A Phase 1/2A Study of Minerval in Adult Patients With Advanced Solid Tumours

This study has been completed.
Sponsor:
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.
Information provided by (Responsible Party):
Lipopharma Therapeutics SL
ClinicalTrials.gov Identifier:
NCT01792310
First received: December 24, 2012
Last updated: December 5, 2016
Last verified: December 2016
  Purpose
This is a phase 1/2A, open label, non-randomized study in patients with advanced solid tumours including malignant glioma

Condition Intervention Phase
Glioma Other Solid Tumours Drug: 2-hydroxyoleic acid (2-OHOA/2OHOA) Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Lipopharma Therapeutics SL:

Primary Outcome Measures:
  • 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 ]
    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 2-OHOA in blood measured by LC-MS/MS [ Time Frame: 21 days ]
    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 [ 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) ]
    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 [ 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) ]
    Blood samples for future analysis of micro RNA

  • 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) ]
    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 [ Time Frame: until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion ]

Enrollment: 54
Study Start Date: May 2013
Study Completion Date: September 2016
Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Cohort 1
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.
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 Name: Minerval®
Experimental: Dose Cohort 2
Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 500 mg twice daily
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 Name: Minerval®
Experimental: Dose Cohort 3
Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 1g twice daily
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 Name: Minerval®
Experimental: 2-OHOA Dose Cohort 4
Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 2g twice daily
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 Name: Minerval®
Experimental: 2-OHOA Dose Cohort 5
Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 4g twice daily
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 Name: Minerval®
Experimental: 2-OHOA Dose Cohort 6
Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 4g three times daily
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 Name: Minerval®
Experimental: 2-OHOA Dose Cohort 7
Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 8g twice daily
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 Name: Minerval®
Experimental: 2-OHOA Dose Expansion cohort. Glioma
Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA) at the MTD: 4g three times daily. Up to 10 patients with malignant glioma.
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 Name: Minerval®
Experimental: 2-OHOA Dose Expansion cohort. Non-glioma
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.
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 Name: Minerval®

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 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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01792310

Locations
Spain
Vall D'Hebron Institute of Oncology
Barcelona, Spain
Instituto Oncológico IMQ, Clínica IMQ Zorrotzaurre
Bilbao, Spain
Onkologikoa
San Sebastián, Spain
United Kingdom
Sir Bobby Robson Cancer Trials Research Centre, The Northern Centre for Cancer Care, Freeman Hospital
Newcastle, Newcastle upon Tyne, United Kingdom, NE7 7DN
The Royal Marsden Hospital Drug Development Unit
Sutton, Surrey, United Kingdom, SM25PT
Sponsors and Collaborators
Lipopharma Therapeutics SL
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.
Investigators
Study Chair: Professor Johann de Bono, MB ChB FRCP MSc PhD The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey, United Kingdom SM2 5NG
Principal Investigator: 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.
  More Information

Additional Information:
Responsible Party: Lipopharma Therapeutics SL
ClinicalTrials.gov Identifier: NCT01792310     History of Changes
Other Study ID Numbers: MIN-001-1203
EudraCT 2012-001527-13 ( Registry Identifier: EudraCT NUMBER: 2012-001527-13 )
Study First Received: December 24, 2012
Last Updated: December 5, 2016

Keywords provided by Lipopharma Therapeutics SL:
Glioma
Solid Tumours
Minerval

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on July 26, 2017