Recurrent High-grade GliomaPhase 1/2AsiDNANCT05394558
AsiDNA Children, Adolescents and Young Adults
A Phase 1/2 study testing AsiDNA in people with Recurrent High-grade Glioma, run by Institut Curie at 10 sites in France.
Trial summary
HGG comprises diffuse midline gliomas (DMG), including diffuse infiltrating brainstem glioma (DIPG), characterised by histone gene mutations, as well as non-DM HGGs mainly in non-midline supratentorial areas, with distinct molecular abnormalities. Read more about this study
- Who is it for?
- Ages 12 months to 24 years
- Conditions the study is for
- Recurrent High-grade Glioma
- What is being tested?
- AsiDNA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 10 sitesFrance
- Study dates
- 27 May 2022to 20 Sep 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 12 months to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Written informed consent from patient (depending on age) and/or parents or legal guardian;
- Patient must be ≥ 12 months and < 25 years of age at the time of enrolment on the study;
- Recurrent high-grade glioma (HGG), including diffuse midline glioma (DMG) and non-DMG, based on RAPNO criteria confirmed by central radiological review, with or without histology if biopsy performed prior to inclusion;
- Available tumour material, at least paraffin embedded and/or also frozen material;
- For DMG and non-DMG HGG, prior radiation dose prescribed ≤ 60 Gy, completed at least 6 months prior to inclusion, with stable disease;
- Maximum cumulative radiation dose to optic chiasm and optic nerve < 56 Gy and < 54 Gy to upper cervical spine (at level C1);
Show all 19Show fewer
- Life expectancy > 2 months at Screening;
- Patient must have a Lansky (≤ 16 years) or Karnofsky (> 16 years) score of ≥ 50 % , not taking into account neurological deficit;
- No significant abnormality on laboratory tests at Screening, including:
- Haemoglobin > 9 g/dL;
- Neutrophils > 1.0 x 109/L;
- Platelets > 100 x 109/L;
- Total bilirubin < 1.5 x ULN;
- AST and ALT< 2.5 x ULN;
- Serum creatinine < 1.5 x ULN for age;
- Normal coagulation tests.
- No organ toxicity > grade 2 according to NCI CTCAE version 5.0 classification, notably cardiovascular, pulmonary or renal diseases, including congenital QT prolongation syndrome, nephrotic syndrome, glomerulopathy, uncontrolled high blood pressure despite appropriate treatment, interstitial pulmonary disease, pulmonary hypertension;
- Negative serum pregnancy test for women of child-bearing potential, and highly effective birth control method for male and female patients of reproductive potential;
- Patients covered by social security or health insurance in compliance with the national legislation relating to biomedical research.
Who cannot join
- 5. Prior radiation dose prescribed > 60 Gy; 6. Massive intra-tumour haemorrhage; 7. Pseudoprogression (including after central review); 8. Metastatic relapse; 9. Other anticancer treatment, on-going or within less than 4 weeks prior to inclusion; 10. Prior or concurrent malignant disease, other than HGG, diagnosed or treated within 5 years prior to inclusion; patients with CMMRD are eligible; 11. Uncontrolled intercurrent disease or active infection; 12. Concomitant disease or other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study; 13. Patients unable to comply with the protocol for any reason; 14. Organ toxicity > grade 2 according to NCI CTCAE version 5.0 classification, notably cardiovascular, pulmonary or renal diseases, including congenital QT prolongation syndrome, nephrotic syndrome, glomerulopathy, uncontrolled high blood pressure despite appropriate treatment, interstitial pulmonary disease, pulmonary hypertension 15. Breastfeeding or pregnancy
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
France10 sites
Chu Angers
Angers, 49033
Chru Bordeaux
Bordeaux, 33076
Centre Oscar Lambret
Lille, 59020
Centre Leon Berard
Lyon, 69373
Chu La Timone Hopital Enfants
Marseille, 13385
Chu Nancy
Nancy, 54500
Institut Curie
Paris, 75005
Chu Strasbourg
Strasbourg, 67098
Chu Toulouse
Toulouse, 31059
Gustave Roussy
Villejuif, 94800
About this study
Official title: A Phase Ib/II Study on AsiDNA in Association With Re-irradiation in Children, Adolescents and Young Adults With High-grade Glioma
HGG comprises diffuse midline gliomas (DMG), including diffuse infiltrating brainstem glioma (DIPG), characterised by histone gene mutations, as well as non-DM HGGs mainly in non-midline supratentorial areas, with distinct molecular abnormalities. First-line treatment comprises surgery when doable (non-DM HGGs), and radiotherapy in all cases. Chemotherapy or other drugs in clinical trials may be added during and/or after radiotherapy depending on the HGG subtype. The recurrence rate is nevertheless high in all paediatric and adolescent HGGs. If the time interval between the end of first-line radiotherapy and relapse is long enough, re-irradiation often provides good palliation of symptoms, delays disease progression, improves quality of life and has minimal and manageable toxicity. Nevertheless, strategies to increase efficacy without increasing toxicity in the treatment of recurrent paediatric HGG are much needed.
AsiDNA™ is a DNA repair inhibitor that increases the vulnerability of tumour cells to irradiation without increasing toxicity in healthy tissues. Its novel mechanism of action, based on perturbation of the DNA damage recognition steps in DNA repair, makes its activity specific to tumour cells. Intravenous administration of AsiDNA is currently being investigated in adults with advanced solid tumours. The MTD was not reached during the escalating dose study on the safety, pharmacokinetics and pharmacodynamics of AsiDNA administered as a 1-hour infusion, however an optimal dose range (400-600 mg) was identified for further development, based on the favourable safety and PK profiles. Preclinical studies on AsiDNA added to radiotherapy have shown increased survival and no increase in short- or long-term toxicity due to the high doses of irradiation.
The study will provide paediatric patients who have recurrent HGG with early access to innovation, even during the early drug development stage in adults.
- Conditions
- Recurrent High-grade Glioma
- Being tested
- AsiDNA
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AsiDNADrug
Administration of AsiDNA followed by radiotherapy
| Study group | Role | What they receive |
|---|---|---|
| Radiotherapy + AsiDNA | Experimental | Patients will receive the IMP which is the AsiDNA (etidaligide). AsiDNA will be administered intravenously as a 1-hour infusion. All patients will receive a loading dose for three consecutive days, with Day 1 being the start day of radiotherapy, followed by once weekly administrations during 11 weeks.
The infusion of AsiDNA should be administered between 4 and 6 hours before the planned start of radiotherapy.
After the administration of AsiDNA, Patients with DIBG will receive a total dose of 18 Gy, delivered in 10 fractions of 1.8 Gy, i.e. 5 fractions per week for 2 weeks, starting on Day 1. Patients with supratentorial non-DMG or DMG will receive a total dose of 36 Gy, delivered in 20 fractions of 1.8 Gy, i.e. 5 fractions per week for 4 weeks, starting on Day 1. Receives: Drug: AsiDNA |
| Radiotherapy | Active comparator | Patients with DIBG will receive a total dose of 18 Gy, delivered in 10 fractions of 1.8 Gy, i.e. 5 fractions per week for 2 weeks, starting on Day 1. Patients with supratentorial non-DMG or DMG will receive a total dose of 36 Gy, delivered in 20 fractions of 1.8 Gy, i.e. 5 fractions per week for 4 weeks, starting on Day 1. Receives: Drug: AsiDNA |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT(Dose-Limiting Toxicities)
Dose-limiting toxicities, i.e. grade ≥ 3 toxicities according to NCI-CTCAE version 5.0, considered as at least possibly related to the treatment during the 8 weeks after treatment initiation.
Measured: 8 weeks after treatment initiation
Activity
3-month progression-free survival (PFS), i.e. the probability for a patient to be alive and free of disease progression based on clinical or radiological criteria, or death from any cause at 3 months after inclusion in the study. Radiological progression will be assessed using RAPNOHGG criteria. Patients lost to follow-up will be counted as failures at the last assessment date.
Measured: 3 months after treatment initiation
Secondary outcomes (12)
Late Onset toxicity
Late-onset toxicity, defined as any toxicity, i.e. any AE considered as at least possibly related to treatment, that occurs more than 8 weeks after treatment initiation;
Measured: 8 weeks and until 12 months after treatment initiation
MR pattern of disease response and of potential treatment-related toxicity,
MR pattern of disease response and of potential treatment-related toxicity, assessed by central review based on morphological and functional imaging features present on the various MR examinations;
Measured: 3 months after treatment initiation
Best objective Response Rate
Best objective response rate, defined as the percentage of patients with complete or partial responses according to RAPNO criteria as assessed by the investigator
Measured: 3 months after treatment initiation
Overall survival
Overall survival, defined as the time from inclusion in the study to death from any cause.
Patients alive or lost to follow-up at the cut-off date will be censored at the last date they were known to be alive;
Measured: 12 months after treatment initiation
Palliation of symptoms 1
Palliation of symptoms, assessed using the Lansky Play Scale (LPS) or Karnofsky score of ≥ 50 %
Measured: 3 months after treatment initiation
Palliation of symptoms 2
Performance Status (KPS)
Measured: 3 months after treatment initiation
Palliation of symptoms 2
Need for corticosteroids and/or bevacizumab
Measured: 3 months after treatment initiation
Pharmacokinetic parameters of AsiDNA.
Maximal observed drug concentration (Cmax);
Measured: 1 week after treatment initiation
Pharmacokinetic parameters of AsiDNA.
absorption and elimination half-life (t1/2))
Measured: 1 week after treatment initiation
Pharmacokinetic parameters of AsiDNA.
time to reach maximum observed drug concentration (Tmax);
Measured: 1 week after treatment initiation
Pharmacokinetic parameters of AsiDNA.
area under the curve (AUC0-t (experimental time points)
Measured: 1 week after treatment initiation
Pharmacokinetic parameters of AsiDNA.
AUC0-∞ (extrapolated to infinity)
Measured: 1 week after treatment initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2022
- Study start27 May 2022
- Primary completion20 Sep 2023
- Study completion20 Sep 2023
Why it stopped: IDMC recommendations
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent High-grade GliomaStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Curie
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05394558
- Sponsor's protocol ID
- IC 2020-21
- Acronym
- AsiDNA
- Status last verified
- Dec 2023
- First submitted
- 16 Dec 2021
- Last updated
- 26 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study on AsiDNA in Association With Re-irradiation in Children, Adolescents and Young Adults With High-grade Glioma
- ClinicalTrials.gov ID
- NCT05394558
- Acronym / sponsor ID
- AsiDNA / IC 2020-21
- Conditions
- Recurrent High-grade Glioma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: IDMC recommendations
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Institut CurieUniversity, hospital or other
- Study start
- 27 May 2022 (actual)
- Primary completion
- 20 Sep 2023 (actual)
- Study completion
- 20 Sep 2023 (actual)
- First posted
- 27 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
HGG comprises diffuse midline gliomas (DMG), including diffuse infiltrating brainstem glioma (DIPG), characterised by histone gene mutations, as well as non-DM HGGs mainly in non-midline supratentorial areas, with distinct molecular abnormalities. First-line treatment comprises surgery when doable (non-DM HGGs), and radiotherapy in all cases. Chemotherapy or other drugs in clinical trials may be added during and/or after radiotherapy depending on the HGG subtype. The recurrence rate is nevertheless high in all paediatric and adolescent HGGs. If the time interval between the end of first-line radiotherapy and relapse is long enough, re-irradiation often provides good palliation of symptoms, delays disease progression, improves quality of life and has minimal and manageable toxicity. Nevertheless, strategies to increase efficacy without increasing toxicity in the treatment of recurrent paediatric HGG are much needed.
AsiDNA™ is a DNA repair inhibitor that increases the vulnerability of tumour cells to irradiation without increasing toxicity in healthy tissues. Its novel mechanism of action, based on perturbation of the DNA damage recognition steps in DNA repair, makes its activity specific to tumour cells. Intravenous administration of AsiDNA is currently being investigated in adults with advanced solid tumours. The MTD was not reached during the escalating dose study on the safety, pharmacokinetics and pharmacodynamics of AsiDNA administered as a 1-hour infusion, however an optimal dose range (400-600 mg) was identified for further development, based on the favourable safety and PK profiles. Preclinical studies on AsiDNA added to radiotherapy have shown increased survival and no increase in short- or long-term toxicity due to the high doses of irradiation.
The study will provide paediatric patients who have recurrent HGG with early access to innovation, even during the early drug development stage in adults.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Radiotherapy + AsiDNA | Experimental | Drug: AsiDNAPatients will receive the IMP which is the AsiDNA (etidaligide). AsiDNA will be administered intravenously as a 1-hour infusion. All patients will receive a loading dose for three consecutive days, with Day 1 being the start day of radiotherapy, followed by once weekly administrations during 11 weeks. The infusion of AsiDNA should be administered between 4 and 6 hours before the planned start of radiotherapy. After the administration of AsiDNA, Patients with DIBG will receive a total dose of 18 Gy, delivered in 10 fractions of 1.8 Gy, i.e. 5 fractions per week for 2 weeks, starting on Day 1. Patients with supratentorial non-DMG or DMG will receive a total dose of 36 Gy, delivered in 20 fractions of 1.8 Gy, i.e. 5 fractions per week for 4 weeks, starting on Day 1. |
| Radiotherapy | Active comparator | Drug: AsiDNAPatients with DIBG will receive a total dose of 18 Gy, delivered in 10 fractions of 1.8 Gy, i.e. 5 fractions per week for 2 weeks, starting on Day 1. Patients with supratentorial non-DMG or DMG will receive a total dose of 36 Gy, delivered in 20 fractions of 1.8 Gy, i.e. 5 fractions per week for 4 weeks, starting on Day 1. |
Who may qualify
- Ages
- 12 months to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (19 listed)
- Written informed consent from patient (depending on age) and/or parents or legal guardian;
- Patient must be ≥ 12 months and < 25 years of age at the time of enrolment on the study;
- Recurrent high-grade glioma (HGG), including diffuse midline glioma (DMG) and non-DMG, based on RAPNO criteria confirmed by central radiological review, with or without histology if biopsy performed prior to inclusion;
- Available tumour material, at least paraffin embedded and/or also frozen material;
- For DMG and non-DMG HGG, prior radiation dose prescribed ≤ 60 Gy, completed at least 6 months prior to inclusion, with stable disease;
Key exclusion criteria (1 listed)
- 5. Prior radiation dose prescribed > 60 Gy; 6. Massive intra-tumour haemorrhage; 7. Pseudoprogression (including after central review); 8. Metastatic relapse; 9. Other anticancer treatment, on-going or within less than 4 weeks prior to inclusion; 10. Prior or concurrent malignant disease, other than HGG, diagnosed or treated within 5 years prior to inclusion; patients with CMMRD are eligible; 11. Uncontrolled intercurrent disease or active infection; 12. Concomitant disease or other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study; 13. Patients unable to comply with the protocol for any reason; 14. Organ toxicity > grade 2 according to NCI CTCAE version 5.0 classification, notably cardiovascular, pulmonary or renal diseases, including congenital QT prolongation syndrome, nephrotic syndrome, glomerulopathy, uncontrolled high blood pressure despite appropriate treatment, interstitial pulmonary disease, pulmonary hypertension 15. Breastfeeding or pregnancy
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 |
|---|---|---|
| AsiDNAAdministration of AsiDNA followed by radiotherapy | Drug | Radiotherapy, Radiotherapy + AsiDNA |
Primary outcome
DLT(Dose-Limiting Toxicities)
Time frame: 8 weeks after treatment initiation
Dose-limiting toxicities, i.e. grade ≥ 3 toxicities according to NCI-CTCAE version 5.0, considered as at least possibly related to the treatment during the 8 weeks after treatment initiation.
Activity
Time frame: 3 months after treatment initiation
3-month progression-free survival (PFS), i.e. the probability for a patient to be alive and free of disease progression based on clinical or radiological criteria, or death from any cause at 3 months after inclusion in the study. Radiological progression will be assessed using RAPNOHGG criteria. Patients lost to follow-up will be counted as failures at the last assessment date.
12 secondary outcomes
Late Onset toxicity
Time frame: 8 weeks and until 12 months after treatment initiation
MR pattern of disease response and of potential treatment-related toxicity,
Time frame: 3 months after treatment initiation
Best objective Response Rate
Time frame: 3 months after treatment initiation
Overall survival
Time frame: 12 months after treatment initiation
Palliation of symptoms 1
Time frame: 3 months after treatment initiation
Palliation of symptoms 2
Time frame: 3 months after treatment initiation
Palliation of symptoms 2
Time frame: 3 months after treatment initiation
Pharmacokinetic parameters of AsiDNA.
Time frame: 1 week after treatment initiation
Pharmacokinetic parameters of AsiDNA.
Time frame: 1 week after treatment initiation
Pharmacokinetic parameters of AsiDNA.
Time frame: 1 week after treatment initiation
Pharmacokinetic parameters of AsiDNA.
Time frame: 1 week after treatment initiation
Pharmacokinetic parameters of AsiDNA.
Time frame: 1 week after treatment initiation
Results and safety
The study was stopped early (reason given: IDMC recommendations). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2023.
- Individual participant dataSharing planned: Yes. Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 AsiDNA in people with Recurrent High-grade Glioma, run by Institut Curie at 10 sites in France.
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 19 inclusion and 1 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: stopped early, as of the sponsor's last update on 26 Dec 2023. 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 France. 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?
The study was stopped early (reason given: IDMC recommendations). Results are not available in the source record.
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?
DLT(Dose-Limiting Toxicities) (time frame: 8 weeks after treatment initiation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Dec 2023.