Clinical trial NCT04094077: Evaluating AGuIX® Nanoparticles in Combination With Stereotactic Radiation for Brain Metastases
Official title: A Phase II Study Evaluating AGuIX® Nanoparticles in Combination With Stereotactic Radiation for Oligo Brain Metastases.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Brain Metastases
Keywords: Stereotactic Radiation
Nanoparticles
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
First posted: 2019-09-18
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Rate of local control
timeFrame: 1 year
Secondary outcomes:
measure: Distant Brain failure
timeFrame: 6 month and at 1 year
measure: Time to brain relapse
timeFrame: 6 month and 1 year
measure: Tumor target volume
timeFrame: 4 days
measure: Brain lesion 3-D volume variation
timeFrame: 45 days and 3 month
measure: Adverse events
timeFrame: From Day 1 to Day 45
measure: FACT-Br
timeFrame: 45 days, 3 month, 6 month, 9 month and 12 month
measure: MMSE
timeFrame: 45 days, 3 month, 6 month, 9 month and 12 month
Other outcomes:
Locations:
city: Lyon
country: France
facility: Centre Léon Bérard
city: Nice
country: France
facility: Centre Antoine Lacassagne
Study officials:
References: