NeuroblastomaPhase 1/2My-CRANCT03291080
Oral Liquid 13-cis-retinoic Acid (13-CRA)
A Phase 1/2 study testing Liquid 13-Cis Retinoic Acid and Extracted capsules 13-CRA in people with Neuroblastoma, run by Nova Laboratories Limited at 10 sites in United Kingdom.
Trial summary
An open label, randomised, multiple dose, cross-over relative bioavailability and pharmacokinetics trial of a novel oral liquid and capsule formulations of 13-CRA administered to patients from 0 months - < 21 years. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Liquid 13-Cis Retinoic Acid and Extracted capsules 13-CRA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 10 sitesUnited Kingdom
- Study dates
- 17 Apr 2018to 12 Sep 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Male or female aged from 0 years to < 21 years of age.
- Patient with high risk neuroblastoma, or unresectable, unfavourable histology intermediate risk neuroblastoma the latter age ≥ 18 months at diagnosis
- Patient who is scheduled to receive at least two treatment cycles of 13-CRA.
- Patient who cannot swallow 13-CRA capsules (i.e. requires extraction of 13-CRA from the capsules).
- Negative pregnancy test for females of child-bearing potential before initiation of treatment, and sexually active patients and partners agreeing to undertake adequate contraceptive measures (see section 4.5).
- Provision of a single or double lumen central venous catheter for sampling (i.e. already in place).
- Parent(s)/legal guardian able and willing to provide written informed consent for the patient to take part in the trial.
- Where applicable, the patient should assent to undergo blood sampling for pharmacokinetic purposes and to allow physiological measurements to be made.
Who cannot join
- Any clinically significant medical condition or abnormality, which, in the opinion of the investigator, might compromise the safety of the patient or which might interfere with the trial.
- Diagnosis of high-risk neuroblastoma (HRNBL) which is currently being treated on the SIOPEN HRNBL trial (patients who have exited this trial will be eligible).
- Known allergy to 13-CRA or any of the excipients.
- Inadequate contraception measures in females of childbearing age.
- Receiving concomitant treatment with tetracyclines.
- Prior to each cycle:
Show all 19Show fewer
- Total bilirubin ≤ 1.5 x normal, and (SGPT) ALT ≤ 5 x normal. Veno-occlusive disease if present, should be stable or improving.
- Skin toxicity no greater than CTCAE Grade 1(10)
- Serum triglycerides <5.65mmol/L.
- No haematuria and / or proteinuria on urinalysis.
- Serum calcium ≤ 2.9mmol/L.
- Serum creatinine based on age / gender as follows:
- Age Maximum Serum Creatinine µmol/L Male Female 1 month to < 6 months 35 35 6 months to < 1 year 44 44 1 to < 2 years 53 53 2 to < 6 years 70 70 6 to < 10 years 88 88 10 to < 13 years 106 106 13 to < 16 years 132 124
- ≥ 16 years 150 124
- Patients with a seizure disorder must be well controlled and taking anticonvulsants. CNS toxicity < grade 2 (CTCAE).
- Withdrawal Criteria:
- Positive pregnancy test - pregnancy testing will be undertaken before treatment commences and routinely before each course of treatment in females of childbearing potential. If a patient is found to be pregnant during the trial, the next course of treatment will not be given until the pregnancy has been discussed with the treating clinician, and the patient will be withdrawn from the trial whether or not treatment is continued.
- Request of the patient, for any reason.
- Discretion of the investigator.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United Kingdom10 sites
Bruce Morland
Birmingham
Dr Antony Ng
Bristol
Dr Amos Burke
Cambridge
Mark Brougham
Edinburgh
Dr Martin Elliott
Leeds
Dr Guiseppe Barone
London
Dr Guy Makin
Manchester
Dr Madhumita Dandapani
Nottingham
Kate Wheeler
Oxford
Sucheta Vaidya
Sutton
About this study
Official title: Relative Bioavailability and Comparative Pharmacokinetics of 13-CRA Oral Liquid and Extracted Capsule Formulations: a Randomised, Open Label, Multi-dose, Cross-over Clinical Trial in Patients Requiring Treatment Cycles of 13-CRA.
An open label, randomised, multiple dose, cross-over relative bioavailability and pharmacokinetics trial of a novel oral liquid and capsule formulations of 13-CRA administered to patients from 0 months - < 21 years.
Read the detailed description
All patients requiring at least two cycles of 13-CRA therapy will be eligible for recruitment into the trial.
13-CRA will be prescribed to patients according to local treatment protocols at each clinical site. The dose administered will be 200mg/m2/day for both test and reference product. Patients with a body weight of ≤12kg will receive a dose of 160 mg/m2/day.
The pharmacokinetics of 13-CRA liquid (test product) and extracted from capsule (reference product) will be evaluated over two months. Prior to the initiation of 13-CRA treatment as part of the trial, patients will be randomised to receive either liquid or capsule formulation in "My-CRA month 1". The patients will then cross-over to the alternative formulation in "My-CRA month 2". The patients on the trial who require further treatment will revert to standard therapy i.e. 13-CRA extracted from capsules according to local practice.
- Conditions
- Neuroblastoma
- Being tested
- Liquid 13-Cis Retinoic Acid, Extracted capsules 13-CRA
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liquid 13-Cis Retinoic AcidDrug
Also called Isotretinoin
Liquid 13-Cis Retinoic Acid
Extracted capsules 13-CRADrug
Also called Isotretinoin
Extracted capsules 13-CRA
| Study group | Role | What they receive |
|---|---|---|
| Liquid | Experimental | Oral liquid formulation of 13-Cis Retinoic Acid - test product. Receives: Drug: Liquid 13-Cis Retinoic Acid |
| Capsule | Experimental | Isotretinoin capsules (13-CRA extracted per standard of care)- reference product. Receives: Drug: Extracted capsules 13-CRA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative Bioavailability
Relative bioavailability (Area under the curve) of 13-CRA administered as oral liquid (test) and extracted capsule (reference) formulations.
Measured: On day 1 and 14 of treatment
Secondary outcomes (5)
Maximum Plasma Concentration (Cmax)
Pharmacokinetic parameter for 13 CRA extracted capsules versus oral liquid formulation
Measured: On day 1 and 14 of treatment
Time to Maximum Concentration (Tmax)
Pharmacokinetic parameter for 13 CRA extracted capsules versus oral liquid formulation
Measured: On day 1 and 14 of treatment
Area Under Plasma Concentration Time Curve (AUC) Metabolite
Pharmacokinetic parameter for 13 CRA extracted capsules versus oral liquid formulation- metabolite 4-oxo-13-cisRA
Measured: On day 1 and 14 of treatment
Cmax (ng/mL)- Metabolite
Pharmacokinetic parameter for metabolite 4-oxo-13-cisRA PK
Measured: On day 1 and 14 of treatment
T Max of Metabolite
T max for metabolite -4-oxo-13-cisRA PK
Measured: On day 1 and 14 of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2017
- Study start17 Apr 2018
- Primary completion12 Sep 2019
- Study completion12 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nova Laboratories Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Hussain Mulla, PhD, Study director, Nova Laboratories Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03291080
- Sponsor's protocol ID
- INV500
- Acronym
- My-CRA
- Status last verified
- Sep 2021
- First submitted
- 19 Jul 2017
- Last updated
- 19 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Veal GJ, Tweddle DA, Visser J, Errington J, Buck H, Marange J, Moss J, Joseph S, Mulla H. Pharmacokinetics and Safety of a Novel Oral Liquid Formulation of 13-cis Retinoic Acid in Children with Neuroblastoma: A Randomized Crossover Clinical Trial. Cancers (Basel). 2021 Apr 14;13(8):1868. doi: 10.3390/cancers13081868.
PubMed 33919763
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Relative Bioavailability and Comparative Pharmacokinetics of 13-CRA Oral Liquid and Extracted Capsule Formulations: a Randomised, Open Label, Multi-dose, Cross-over Clinical Trial in Patients Requiring Treatment Cycles of 13-CRA.
- ClinicalTrials.gov ID
- NCT03291080
- Acronym / sponsor ID
- My-CRA / INV500
- Conditions
- Neuroblastoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Nova Laboratories LimitedIndustry (pharma, biotech, devices)
- Study start
- 17 Apr 2018 (actual)
- Primary completion
- 12 Sep 2019 (actual)
- Study completion
- 12 Sep 2019 (actual)
- First posted
- 25 Sep 2017 (actual)
- Results
- Posted 19 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An open label, randomised, multiple dose, cross-over relative bioavailability and pharmacokinetics trial of a novel oral liquid and capsule formulations of 13-CRA administered to patients from 0 months - < 21 years.
Detailed description
All patients requiring at least two cycles of 13-CRA therapy will be eligible for recruitment into the trial.
13-CRA will be prescribed to patients according to local treatment protocols at each clinical site. The dose administered will be 200mg/m2/day for both test and reference product. Patients with a body weight of ≤12kg will receive a dose of 160 mg/m2/day.
The pharmacokinetics of 13-CRA liquid (test product) and extracted from capsule (reference product) will be evaluated over two months. Prior to the initiation of 13-CRA treatment as part of the trial, patients will be randomised to receive either liquid or capsule formulation in "My-CRA month 1". The patients will then cross-over to the alternative formulation in "My-CRA month 2". The patients on the trial who require further treatment will revert to standard therapy i.e. 13-CRA extracted from capsules according to local practice.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Liquid | Experimental | Drug: Liquid 13-Cis Retinoic AcidOral liquid formulation of 13-Cis Retinoic Acid - test product. |
| Capsule | Experimental | Drug: Extracted capsules 13-CRAIsotretinoin capsules (13-CRA extracted per standard of care)- reference product. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Male or female aged from 0 years to < 21 years of age.
- Patient with high risk neuroblastoma, or unresectable, unfavourable histology intermediate risk neuroblastoma the latter age ≥ 18 months at diagnosis
- Patient who is scheduled to receive at least two treatment cycles of 13-CRA.
- Patient who cannot swallow 13-CRA capsules (i.e. requires extraction of 13-CRA from the capsules).
- Negative pregnancy test for females of child-bearing potential before initiation of treatment, and sexually active patients and partners agreeing to undertake adequate contraceptive measures (see section 4.5).
Key exclusion criteria (19 listed)
- Any clinically significant medical condition or abnormality, which, in the opinion of the investigator, might compromise the safety of the patient or which might interfere with the trial.
- Diagnosis of high-risk neuroblastoma (HRNBL) which is currently being treated on the SIOPEN HRNBL trial (patients who have exited this trial will be eligible).
- Known allergy to 13-CRA or any of the excipients.
- Inadequate contraception measures in females of childbearing age.
- Receiving concomitant treatment with tetracyclines.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liquid 13-Cis Retinoic AcidAlso: IsotretinoinLiquid 13-Cis Retinoic Acid | Drug | Liquid |
| Extracted capsules 13-CRAAlso: IsotretinoinExtracted capsules 13-CRA | Drug | Capsule |
Primary outcome
Relative Bioavailability
Time frame: On day 1 and 14 of treatment
Relative bioavailability (Area under the curve) of 13-CRA administered as oral liquid (test) and extracted capsule (reference) formulations.
5 secondary outcomes
Maximum Plasma Concentration (Cmax)
Time frame: On day 1 and 14 of treatment
Time to Maximum Concentration (Tmax)
Time frame: On day 1 and 14 of treatment
Area Under Plasma Concentration Time Curve (AUC) Metabolite
Time frame: On day 1 and 14 of treatment
Cmax (ng/mL)- Metabolite
Time frame: On day 1 and 14 of treatment
T Max of Metabolite
Time frame: On day 1 and 14 of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33919763Veal GJ, Tweddle DA, Visser J, Errington J, Buck H, Marange J, Moss J, Joseph S, Mulla H. Pharmacokinetics and Safety of a Novel Oral Liquid Formulation of 13-cis Retinoic Acid in Children with Neuroblastoma: A Randomized Crossover Clinical Trial. Cancers (Basel). 2021 Apr 14;13(8):1868. doi: 10.3390/cancers13081868.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hussain Mulla, PhD study director
Nova Laboratories Limited
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Liquid 13-Cis Retinoic Acid and Extracted capsules 13-CRA in people with Neuroblastoma, run by Nova Laboratories Limited at 10 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relative Bioavailability (time frame: On day 1 and 14 of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03291080, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2021; AzTrials last refreshed its copy on 6 Nov 2026.