Evaluating AGuIX® Nanoparticles in Combination With Stereotactic Radiation for Brain Metastases

Brain Metastases Clinical Trial

— NANOSTEREO  

Official title:

A Phase II Study Evaluating AGuIX® Nanoparticles in Combination With Stereotactic Radiation for Oligo Brain Metastases.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04094077
• Other study ID #: ET18-270 NANOSTEREO
• Status: Terminated
• Phase: Phase 2
• Start date: January 17, 2020
• Est. completion date: February 24, 2021

Study information

• Verified date: June 2021
• Source: Centre Leon Berard
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates the clinical impact of AGuIX® nanoparticles in combination with Fractionated Stereotactic Radiation in oligo brain metastases.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: February 24, 2021
• Est. primary completion date: February 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Neoplasm Metastasis

Intervention

Drug:
• AGuIX
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.

Locations

Country	Name	City	State
France	Centre Léon Bérard	Lyon
France	Centre Antoine Lacassagne	Nice

Sponsors (1)

Lead Sponsor	Collaborator
Centre Leon Berard

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	1 year
Secondary	Distant Brain failure	Distant Brain failure is defined as the presence of new brain metastases or leptomeningeal enhancement outside the irradiated volume.	6 month and at 1 year
Secondary	Time to brain relapse	The event of interest will be the local progression on any irradiated lesion.	6 month and 1 year
Secondary	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.	4 days
Secondary	Brain lesion 3-D volume variation	Brain lesion 3-D volume variation will be analysed using volumetric T1 post-gadolinium MRI.	45 days and 3 month
Secondary	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.	From Day 1 to Day 45
Secondary	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.	45 days, 3 month, 6 month, 9 month and 12 month
Secondary	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.	45 days, 3 month, 6 month, 9 month and 12 month