Back to resultsEvaluating AGuIX® Nanoparticles in Combination With Stereotactic Radiation for Brain Metastases (NANOSTEREO)
Primary Purpose
Brain Metastases
Status
Terminated
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
AGuIX
Sponsored by
About this trial
This is an interventional treatment trial for Brain Metastases focused on measuring Stereotactic Radiation, Nanoparticles
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- Centre Léon Bérard
- Centre Antoine Lacassagne
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Aguix + Stereotactic Radiation
Arm Description
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Distant Brain failure
Distant Brain failure is defined as the presence of new brain metastases or leptomeningeal enhancement outside the irradiated volume.
Time to brain relapse
The event of interest will be the local progression on any irradiated lesion.
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.
Brain lesion 3-D volume variation
Brain lesion 3-D volume variation will be analysed using volumetric T1 post-gadolinium MRI.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04094077
Brief Title
Evaluating AGuIX® Nanoparticles in Combination With Stereotactic Radiation for Brain Metastases
Acronym
NANOSTEREO
Official Title
A Phase II Study Evaluating AGuIX® Nanoparticles in Combination With Stereotactic Radiation for Oligo Brain Metastases.
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Terminated
Why Stopped
Study stopped after a negative result delivred by the CPP for a substancial modification of the protocol
Study Start Date
January 17, 2020 (Actual)
Primary Completion Date
February 24, 2021 (Actual)
Study Completion Date
February 24, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Leon Berard
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Metastases
Keywords
Stereotactic Radiation, Nanoparticles
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aguix + Stereotactic Radiation
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AGuIX
Intervention Description
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.
Primary Outcome Measure Information:
Title
Rate of local control
Description
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).
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Distant Brain failure
Description
Distant Brain failure is defined as the presence of new brain metastases or leptomeningeal enhancement outside the irradiated volume.
Time Frame
6 month and at 1 year
Title
Time to brain relapse
Description
The event of interest will be the local progression on any irradiated lesion.
Time Frame
6 month and 1 year
Title
Tumor target volume
Description
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.
Time Frame
4 days
Title
Brain lesion 3-D volume variation
Description
Brain lesion 3-D volume variation will be analysed using volumetric T1 post-gadolinium MRI.
Time Frame
45 days and 3 month
Title
Adverse events
Description
The assessment of safety will be based mainly on the frequency of adverse events based on the common toxicity criteria (CTCAE-V5.0) grade.
Time Frame
From Day 1 to Day 45
Title
FACT-Br
Description
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.
Time Frame
45 days, 3 month, 6 month, 9 month and 12 month
Title
MMSE
Description
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.
Time Frame
45 days, 3 month, 6 month, 9 month and 12 month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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.
Exclusion Criteria:
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.
Facility Information:
Facility Name
Centre Léon Bérard
City
Lyon
ZIP/Postal Code
69008
Country
France
Facility Name
Centre Antoine Lacassagne
City
Nice
ZIP/Postal Code
06189
Country
France
12. IPD Sharing Statement
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Evaluating AGuIX® Nanoparticles in Combination With Stereotactic Radiation for Brain Metastases
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