Brain MetastasesPhase 2NANOSTEREONCT04094077
Evaluating AGuIX® Nanoparticles in Combination With Stereotactic Radiation for Brain Metastases
A Phase 2 study testing AGuIX in people with Brain Metastases, run by Centre Leon Berard at 2 sites in France.
Trial summary
This study evaluates the clinical impact of AGuIX® nanoparticles in combination with Fractionated Stereotactic Radiation in oligo brain metastases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases
- What is being tested?
- AGuIX
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 2 sitesFrance
- Study dates
- 17 Jan 2020to 24 Feb 2021
- Phase
- Phase 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients aged of at least 18 years on day of signing informed consent.
- Histologically-confirmed diagnosis of any histological type of solid tumors, excluding primary central nervous system (CNS) tumors.
- Radiological evidence by MRI : At least one and a maximum of 5 brain metastases, and at least one brain lesion with a longest diameter ≥ 2 cm and eligible for FSRT.
- Patient without progression on extracranial disease documented by radiological assessment as per RECIST v1.1 within 4 weeks before inclusion.
- For patients treated with a systemic anti-cancer therapy: a minimal 2-week washout period is required from the date of last systemic treatment administration to Day 1, except for hormonal agents.
- ECOG Performance Status (PS) ≤2.
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- Absolute neutrophil count (ANC) ≥ 1.0 G/L, Platelets ≥ 75 G/L, Hemoglobin ≥ 8 g/dL, Serum creatinine OR Creatinine clearance according to CKD-EPI ≤ 1.5 x Upper Limit of Normal (ULN) OR ≥ 50 mL/min/1.73m2, ASAT and ALAT ≤ 3 x ULN (or ≤ 5.0 ULN in case of liver metastasis or hepatic infiltration),INR and Activated Partial Thromboplastin Time (aPTT) ≤1.5 x ULN.
- Women of child-bearing potential must have a negative serum pregnancy test at screening and must agree to use 2 effective forms of contraception from the time of the negative pregnancy test up to 3 months after the last dose of the study drug.
- Fertile men must agree to use contraceptive measures up to 3 months after the last dose of study drug.
- Patients who understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures. Patient should be able and willing to comply with study visits and procedures as per protocol.
- Patients must be covered by a medical insurance.
Who cannot join
- Prior local treatment with radiotherapy (whole / partial brain or stereotactic radiosurgery) or surgical resection of brain lesions.
- Patient participating to another clinical trial with an investigational agent.
- Patients who have not recovered from significant adverse events (i.e. Grade > 2 AE according to NCI CTCAE v5.0) due to prior treatment with anti-cancer agents with exception of any Grade alopecia or lab values presented in inclusion criteria.
- Contra-indication for MRI enhanced with gadolinium (e.g. cardiac pacemaker, implanted defibrillator, certain cardiac valve replacements, certain metal implants).
- Patients who are pregnant or breastfeeding.
Trial locations and contacts
2 sites in 1 country.
France2 sites
Centre Léon Bérard
Lyon, 69008
Centre Antoine Lacassagne
Nice, 06189
About this study
Official title: A Phase II Study Evaluating AGuIX® Nanoparticles in Combination With Stereotactic Radiation for Oligo Brain Metastases.
This study evaluates the clinical impact of AGuIX® nanoparticles in combination with Fractionated Stereotactic Radiation in oligo brain metastases.
Read the detailed description
AGuIX® (Activation and Guidance of Irradiation by X-ray, NH TherAguix) are Gadolinium chelated polysiloxane based nanoparticles with Magnetic Resonance contrast properties, able to accumulate in the tumor through the enhanced permeability and retention effect and sufficiently small (sub-5 nm diameter) to allow for renal clearance.
AGuIX® nanomedicine can be used as:
- Positive contrast agent for Magnetic Resonance Imaging (MRI). It displays higher efficacy than commercial contrast agents and so it can be used to delineate precisely the tumors.
- A booster of Radiotherapy during the radiotherapy protocol, after the localization of the tumor.
This is permitted by the high radiosensitizing potential of AGuIX® that allows a local increase of efficacy of X-ray damages. French and international groups have demonstrated the radiosensitizer effect of AGuIX® to improve the efficacy of radiotherapy.
Thanks to a difference in porosity between the vascular networks, AGuIX® penetrates and resides in tumor tissues, but not in healthy tissues.
- Conditions
- Brain Metastases
- Being tested
- AGuIX
- Keywords
- Stereotactic Radiation, Nanoparticles
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AGuIXDrug
2 IV injections (100 mg/Kg/injection) at day 4 and day 8 + Strereotactic Radiation from day 8 to day 15 as per standard practice.
| Study group | Role | What they receive |
|---|---|---|
| Aguix + Stereotactic Radiation | Experimental | Not described Receives: Drug: AGuIX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of local control
The primary endpoint is the rate of local control defined as the proportion of patients with a complete response, a partial response or a stable disease. Response of Brain lesion will be evaluated using the RECIST classifications with partial response (PR, > 30% decrease in longest diameter), stable disease (SD <30% decrease and <20% increase in longest diameter), progressive disease (PD > 20% increase in longest diameter) and Complete response (CR) (complete disappearance of the brain lesion).
Measured: 1 year
Secondary outcomes (7)
Distant Brain failure
Distant Brain failure is defined as the presence of new brain metastases or leptomeningeal enhancement outside the irradiated volume.
Measured: 6 month and at 1 year
Time to brain relapse
The event of interest will be the local progression on any irradiated lesion.
Measured: 6 month and 1 year
Tumor target volume
The Tumor target volume agreement is the comparison between both the MRI images with AGuIX® and Gd-chelates. It is defined as the correlation between the irradiation volume calculated based on the MRI before nanoparticles injection and the volume calculated after nanoparticles injection.
Measured: 4 days
Brain lesion 3-D volume variation
Brain lesion 3-D volume variation will be analysed using volumetric T1 post-gadolinium MRI.
Measured: 45 days and 3 month
Adverse events
The assessment of safety will be based mainly on the frequency of adverse events based on the common toxicity criteria (CTCAE-V5.0) grade.
Measured: From Day 1 to Day 45
FACT-Br
The FACT-Br consists of a general version (FACT-G) and a brain subscale (BRCS). The FACT-G consist of 27 questions with 4 domains assessing physical well-being (score range: 0-28), social/family well-being (score range: 0-28), emotional well-being (score range: 0-24) and functional well-being (score range: 0-28). The BRCs is a 23-item questionnaire related to neurological concerns that provides an additional set of disease-specific questions pertaining to brain neoplasms (score range: 0-92). The FACT-Br total score is the sum of the FACT-G total score and the BrCS score. Positive change scores indicate improved quality of life.
Measured: 45 days, 3 month, 6 month, 9 month and 12 month
MMSE
The MMSE is an 11-item measure that tests five areas of cognitive function: orientation, registration, attention and calculation, recall and language. The minimum score is 0 and the maximum score is 30 with higher MMSE scores indicating better cognition.
Measured: 45 days, 3 month, 6 month, 9 month and 12 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2019
- Study start17 Jan 2020
- Primary completion24 Feb 2021
- Study completion24 Feb 2021
Why it stopped: Study stopped after a negative result delivred by the CPP for a substancial modification of the protocol
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain MetastasesStudies of the same condition, open and under way.
- More trials run by Centre Leon BerardThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This study is a paucicentric, single arm Phase II trial conducted according to a single stage Fleming-A'Hern design and aiming to evaluate the efficacy of AGuIX® during FSRT of brain metastasis.
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Leon Berard
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04094077
- Sponsor's protocol ID
- ET18-270 NANOSTEREO
- Acronym
- NANOSTEREO
- Status last verified
- Jun 2021
- First submitted
- 16 Sep 2019
- Last updated
- 8 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study Evaluating AGuIX® Nanoparticles in Combination With Stereotactic Radiation for Oligo Brain Metastases.
- ClinicalTrials.gov ID
- NCT04094077
- Acronym / sponsor ID
- NANOSTEREO / ET18-270 NANOSTEREO
- Conditions
- Brain Metastases
- Keywords
- Stereotactic Radiation, Nanoparticles
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study stopped after a negative result delivred by the CPP for a substancial modification of the protocol
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Centre Leon BerardUniversity, hospital or other
- Study start
- 17 Jan 2020 (actual)
- Primary completion
- 24 Feb 2021 (actual)
- Study completion
- 24 Feb 2021 (actual)
- First posted
- 18 Sep 2019 (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.
This study evaluates the clinical impact of AGuIX® nanoparticles in combination with Fractionated Stereotactic Radiation in oligo brain metastases.
Detailed description
AGuIX® (Activation and Guidance of Irradiation by X-ray, NH TherAguix) are Gadolinium chelated polysiloxane based nanoparticles with Magnetic Resonance contrast properties, able to accumulate in the tumor through the enhanced permeability and retention effect and sufficiently small (sub-5 nm diameter) to allow for renal clearance.
AGuIX® nanomedicine can be used as:
- Positive contrast agent for Magnetic Resonance Imaging (MRI). It displays higher efficacy than commercial contrast agents and so it can be used to delineate precisely the tumors.
- A booster of Radiotherapy during the radiotherapy protocol, after the localization of the tumor.
This is permitted by the high radiosensitizing potential of AGuIX® that allows a local increase of efficacy of X-ray damages. French and international groups have demonstrated the radiosensitizer effect of AGuIX® to improve the efficacy of radiotherapy.
Thanks to a difference in porosity between the vascular networks, AGuIX® penetrates and resides in tumor tissues, but not in healthy tissues.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This study is a paucicentric, single arm Phase II trial conducted according to a single stage Fleming-A'Hern design and aiming to evaluate the efficacy of AGuIX® during FSRT of brain metastasis.
| Arm | Type | Receives |
|---|---|---|
| Aguix + Stereotactic Radiation | Experimental | Drug: AGuIX |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male or female patients aged of at least 18 years on day of signing informed consent.
- Histologically-confirmed diagnosis of any histological type of solid tumors, excluding primary central nervous system (CNS) tumors.
- Radiological evidence by MRI : At least one and a maximum of 5 brain metastases, and at least one brain lesion with a longest diameter ≥ 2 cm and eligible for FSRT.
- Patient without progression on extracranial disease documented by radiological assessment as per RECIST v1.1 within 4 weeks before inclusion.
- For patients treated with a systemic anti-cancer therapy: a minimal 2-week washout period is required from the date of last systemic treatment administration to Day 1, except for hormonal agents.
Key exclusion criteria (5 listed)
- Prior local treatment with radiotherapy (whole / partial brain or stereotactic radiosurgery) or surgical resection of brain lesions.
- Patient participating to another clinical trial with an investigational agent.
- Patients who have not recovered from significant adverse events (i.e. Grade > 2 AE according to NCI CTCAE v5.0) due to prior treatment with anti-cancer agents with exception of any Grade alopecia or lab values presented in inclusion criteria.
- Contra-indication for MRI enhanced with gadolinium (e.g. cardiac pacemaker, implanted defibrillator, certain cardiac valve replacements, certain metal implants).
- Patients who are pregnant or breastfeeding.
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 |
|---|---|---|
| AGuIX2 IV injections (100 mg/Kg/injection) at day 4 and day 8 + Strereotactic Radiation from day 8 to day 15 as per standard practice. | Drug | Aguix + Stereotactic Radiation |
Primary outcome
Rate of local control
Time frame: 1 year
The primary endpoint is the rate of local control defined as the proportion of patients with a complete response, a partial response or a stable disease. Response of Brain lesion will be evaluated using the RECIST classifications with partial response (PR, > 30% decrease in longest diameter), stable disease (SD <30% decrease and <20% increase in longest diameter), progressive disease (PD > 20% increase in longest diameter) and Complete response (CR) (complete disappearance of the brain lesion).
7 secondary outcomes
Distant Brain failure
Time frame: 6 month and at 1 year
Time to brain relapse
Time frame: 6 month and 1 year
Tumor target volume
Time frame: 4 days
Brain lesion 3-D volume variation
Time frame: 45 days and 3 month
Adverse events
Time frame: From Day 1 to Day 45
FACT-Br
Time frame: 45 days, 3 month, 6 month, 9 month and 12 month
MMSE
Time frame: 45 days, 3 month, 6 month, 9 month and 12 month
Results and safety
The study was stopped early (reason given: Study stopped after a negative result delivred by the CPP for a substancial modification of the protocol). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2021.
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AGuIX in people with Brain Metastases, run by Centre Leon Berard at 2 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 11 inclusion and 5 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 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 phase mean?
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: Study stopped after a negative result delivred by the CPP for a substancial modification of the protocol). 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?
Rate of local control (time frame: 1 year). 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 8 Jun 2021.