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

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ClinicalTrials.gov Identifier: NCT04094077
Recruitment Status : Recruiting
First Posted : September 18, 2019
Last Update Posted : January 22, 2020
Sponsor:
Information provided by (Responsible Party):
Centre Leon Berard

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

Condition or disease Intervention/treatment Phase
Brain Metastases Drug: AGuIX Phase 2

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
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Intervention Model: Single Group Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study Evaluating AGuIX® Nanoparticles in Combination With Stereotactic Radiation for Oligo Brain Metastases.
Actual Study Start Date : January 17, 2020
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2022
Arms and Interventions
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Arm Intervention/treatment
Experimental: Aguix + Stereotactic Radiation 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.


Outcome Measures
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Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. Distant Brain failure [ Time Frame: 6 month and at 1 year ]
    Distant Brain failure is defined as the presence of new brain metastases or leptomeningeal enhancement outside the irradiated volume.

  2. Time to brain relapse [ Time Frame: 6 month and 1 year ]
    The event of interest will be the local progression on any irradiated lesion.

  3. Tumor target volume [ Time Frame: 4 days ]
    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. Brain lesion 3-D volume variation [ Time Frame: 45 days and 3 month ]
    Brain lesion 3-D volume variation will be analysed using volumetric T1 post-gadolinium MRI.

  5. Adverse events [ Time Frame: From Day 1 to Day 45 ]
    The assessment of safety will be based mainly on the frequency of adverse events based on the common toxicity criteria (CTCAE-V5.0) grade.

  6. FACT-Br [ Time Frame: 45 days, 3 month, 6 month, 9 month and 12 month ]
    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.

  7. MMSE [ Time Frame: 45 days, 3 month, 6 month, 9 month and 12 month ]
    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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04094077


Contacts
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Contact: Ronan TANGUY, MD +33(0)4 78 78 75 87 ronan.tanguy@lyon.unicancer.fr

Locations
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France
Centre Léon Bérard Recruiting
Lyon, France, 69008
Contact: Ronan TANGUY, MD    +33 (0) 78 78 75 87    ronan.tanguy@lyon.unicancer.fr   
Principal Investigator: Ronan TANGUY, MD         
Sub-Investigator: Line CLAUDE DEFEZ, MD         
Sub-Investigator: Marie Pierre SUNYACH, MD         
Sub-Investigator: Christian CARRIE, MD         
Sub-Investigator: Isabelle MARTEL-LAFAY, MD         
Centre Antoine Lacassagne Not yet recruiting
Nice, France, 06189
Contact: Pierre Yves BONDIAU, MD    +33 (0) 4 92 03 12 72    pierre-yves.bondiau@nice.unicancer.fr   
Principal Investigator: Pierre Yves BONDIAU, MD         
Sub-Investigator: Jérome DOYEN, MD         
Sponsors and Collaborators
Centre Leon Berard
More Information
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Responsible Party: Centre Leon Berard
ClinicalTrials.gov Identifier: NCT04094077    
Other Study ID Numbers: ET18-270 NANOSTEREO
First Posted: September 18, 2019    Key Record Dates
Last Update Posted: January 22, 2020
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centre Leon Berard:
Stereotactic Radiation
Nanoparticles
Additional relevant MeSH terms:
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Neoplasm Metastasis
Brain Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
 Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases