Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    min-001-1203
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01792310
Recruitment Status : Completed
First Posted : February 15, 2013
Last Update Posted : December 6, 2016
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

Tracking Information
First Submitted Date  ICMJE December 24, 2012
First Posted Date  ICMJE February 15, 2013
Last Update Posted Date December 6, 2016
Study Start Date  ICMJE May 2013
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2013)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 25, 2015)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2013)
  • 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: 22 days ]
    Effect on glial fibrillary acidic protein in glioma patients and effect on sphingomyelin and dihydrofolate reductase in patients with other solid tumours
  • Radiological disease progression [ Time Frame: Every 6 weeks ]
    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: 126 days (based upon 6 cycles) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1/2A Study of Minerval in Adult Patients With Advanced Solid Tumours
Official Title  ICMJE A Phase 1/2A Dose Escalation Study of 2-hydroxyoleic Acid (2-OHOA; Minerval®) in Adult Patients With Advanced Solid Tumours Including Malignant Glioma
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 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioma
  • Other Solid Tumours
Intervention  ICMJE 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®
Study Arms  ICMJE
  • 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.
    Intervention: Drug: 2-hydroxyoleic acid (2-OHOA/2OHOA)
  • Experimental: Dose Cohort 2
    Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 500 mg twice daily
    Intervention: Drug: 2-hydroxyoleic acid (2-OHOA/2OHOA)
  • Experimental: Dose Cohort 3
    Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 1g twice daily
    Intervention: Drug: 2-hydroxyoleic acid (2-OHOA/2OHOA)
  • Experimental: 2-OHOA Dose Cohort 4
    Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 2g twice daily
    Intervention: Drug: 2-hydroxyoleic acid (2-OHOA/2OHOA)
  • Experimental: 2-OHOA Dose Cohort 5
    Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 4g twice daily
    Intervention: Drug: 2-hydroxyoleic acid (2-OHOA/2OHOA)
  • Experimental: 2-OHOA Dose Cohort 6
    Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 4g three times daily
    Intervention: Drug: 2-hydroxyoleic acid (2-OHOA/2OHOA)
  • Experimental: 2-OHOA Dose Cohort 7
    Intervention: 2-hydroxyoleic acid (2-OHOA/2OHOA). 8g twice daily
    Intervention: Drug: 2-hydroxyoleic acid (2-OHOA/2OHOA)
  • 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.
    Intervention: Drug: 2-hydroxyoleic acid (2-OHOA/2OHOA)
  • 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.
    Intervention: Drug: 2-hydroxyoleic acid (2-OHOA/2OHOA)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 5, 2016)
54
Original Estimated Enrollment  ICMJE
 (submitted: February 13, 2013)
50
Actual Study Completion Date  ICMJE September 2016
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain,   United Kingdom
Removed Location Countries Switzerland
 
Administrative Information
NCT Number  ICMJE NCT01792310
Other Study ID Numbers  ICMJE MIN-001-1203
EudraCT 2012-001527-13 ( Registry Identifier: EudraCT NUMBER: 2012-001527-13 )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Lipopharma Therapeutics SL
Study Sponsor  ICMJE Lipopharma Therapeutics SL
Collaborators  ICMJE
  • 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  ICMJE
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.
PRS Account Lipopharma Therapeutics SL
Verification Date December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP