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Trial record 4 of 8 for:    AGuIX

Stereotactic Brain-directed Radiation With or Without Aguix Gadolinium-Based Nanoparticles in Brain Metastases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04899908
Recruitment Status : Not yet recruiting
First Posted : May 25, 2021
Last Update Posted : May 25, 2021
Sponsor:
Collaborator:
NH TherAguix SAS
Information provided by (Responsible Party):
Ayal Aizer, MD, Dana-Farber Cancer Institute

Brief Summary:
The purpose of this study is to determine whether AGuIX (Activation and Guidance of Irradiation by X-ray) gadolinium-based nanoparticles make radiation work more effectively in the treatment of patients with brain metastases that are more difficult to control with stereotactic radiation alone.

Condition or disease Intervention/treatment Phase
Brain Cancer Brain Metastases Melanoma Lung Cancer Breast Cancer HER2-positive Breast Cancer Colorectal Cancer Gastrointestinal Cancer SRS SRT Whole Brain Radiation Stereotactic Radiation AGuIX Nanoparticle Cystic Brain Tumor Radiation: Stereotactic Radiation Drug: AGuIX gadolinium-based nanoparticles Other: Placebo Phase 2

Detailed Description:

This research study is a double-blind, randomized phase II clinical trial of brain-directed stereotactic radiation with or without AGuIX (Activation and Guidance of Irradiation by X-ray) gadolinium-based nanoparticles in the management of brain metastases at higher-risk of local recurrence with radiation alone.

The study agent (AGuIX gadolinium-based nanoparticles) has two main parts. The first is gadolinium, also known as "contrast," which is typically injected into a vein during a MRI scan. The second part is a nanoparticle (linked to the gadolinium) that may make focused radiation work more effectively. The AGuIX gadolinium-based nanoparticles are deposited within the brain metastases via the bloodstream and then the brain metastases are radiated.

The U.S. Food and Drug Administration (FDA) has not approved AGuIX gadolinium-based nanoparticles as a treatment for any disease. AGuIX gadolinium-based nanoparticles have been tested in other studies for safety and efficacy in patients with brain metastases who are also receiving radiation.

This study seeks to determine whether AGuIX gadolinium-based nanoparticles improve outcomes relative to placebo.Participants will be "randomized" into one of the study groups:

  • Group A: Radiation plus AGuIX gadolinium-based nanoparticles
  • Group B: Radiation plus placebo

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

NH TherAguix, the manufacturer of the AGuIX gadolinium-based nanoparticles, is supporting this research study by providing the AGuIX gadolinium-based nanoparticles that will be evaluated in this study.

NH TherAguix is also covering the cost of the study.

It is expected that about 112 people will take part in this research study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 112 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blind, Phase II Randomized Study of Brain-directed Stereotactic Radiation With or Without AGuIX Gadolinium-based Nanoparticles in the Management of Brain Metastases at Higher Risk of Local Recurrence With Radiation Alone
Estimated Study Start Date : June 2021
Estimated Primary Completion Date : February 2025
Estimated Study Completion Date : February 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Stereotactic Radiation plus AGuIX gadolinium-based nanoparticles

Randomly assigned participants will receive:

  • AGuIX gadolinium-based nanoparticles 3-5 days before radiation is initiated
  • AGuIX gadolinium-based up to 2x during radiation, depending on standard of care radiation treatment.

    • If standard of care radiation treatment involves only one day of radiation, participant will receive AGuIX gadolinium-based nanoparticles on the day of radiation.
    • If standard of care radiation treatment involves 5 or 6 days of radiation, participant will receive AGuIX gadolinium-based nanoparticles two-times (2x) in total, on the first and third day of radiation.
Radiation: Stereotactic Radiation
Focused radiation beams to treat tumors
Other Name: Stereotactic Radiotherapy

Drug: AGuIX gadolinium-based nanoparticles
Intravenous injection

Experimental: Stereotactic Radiation plus placebo

Randomly assigned participants will receive:

  • Placebo 3-5 days before radiation is initiated
  • Placebo up to 2x during radiation, depending on standard of care radiation treatment.

    • If standard of care radiation treatment involves only one day of radiation participant will receive Placebo on the day of radiation.
    • If standard of care radiation treatment involves 5 or 6 days of radiation participant will receive Placebo two-times (2x) in total, on the first and third day of radiation.
Radiation: Stereotactic Radiation
Focused radiation beams to treat tumors
Other Name: Stereotactic Radiotherapy

Other: Placebo
Intravenous infusion
Other Name: Saline




Primary Outcome Measures :
  1. Local Recurrence [ Time Frame: From enrollment to 6 months ]
    Assessed with Response Assessment in Neuro-Oncology (RANO) - Brain Metastasis Guidelines Time to local failure on a per metastasis basis will be performed using the log-rank test.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Time from enrollment to 12 months ]
    Assessed with log-rank test

  2. Progression-Free Survival (PFS) [ Time Frame: Time from enrollment to 12 months ]
    Assessed with log-rank test

  3. Time to Progression (TTP) [ Time Frame: Time from enrollment to 12 months ]
    Assessed with log-rank test

  4. Death due to neurologic causes [ Time Frame: From enrollment to 12 months ]
    Assessed with Gray's test

  5. Performance status [ Time Frame: From enrollment to 12 months ]
    Karnofsky performance status, assessed longitudinally (longitudinal regression)

  6. Ability to complete activities of daily living [ Time Frame: From enrollment to 12 months ]
    Questionnaire - EQ-5D, assessed longitudinally (longitudinal regression)

  7. Incidence and time to detection of new brain metastases [ Time Frame: From enrollment to 12 months ]
    Assessed with log-rank test

  8. Incidence and time to detection of radiation necrosis [ Time Frame: From enrollment to 12 months ]
    Assessed with log-rank test

  9. Incidence and time to detection of leptomeningeal disease [ Time Frame: From enrollment to 12 months ]
    Assessed with log-rank test

  10. Incidence and time to detection of progressive intracranial disease [ Time Frame: From enrollment to 12 months ]
    Assessed with log-rank test

  11. Incidence and time to detection of salvage craniotomy [ Time Frame: From enrollment to 12 months ]
    Assessed with log-rank test

  12. Incidence and time to additional radiotherapeutic treatments [ Time Frame: From enrollment to 12 months ]
    Assessed with log-rank test

  13. Incidence and time to the development of seizures [ Time Frame: From enrollment to 12 months ]
    Assessed with log-rank test

  14. Steroid use [ Time Frame: From enrollment to 12 months ]
    Assessed longitudinally (longitudinal regression)

  15. Local recurrence at one year in metastases treated radiotherapeutically [ Time Frame: From enrollment to 12 months ]
    Assessed using RECIST (response evaluation criteria in solid tumors) criteria

  16. Neurocognitive function: verbal learning and memory [ Time Frame: From enrollment to 12 months ]
    Hopkins Verbal Learning Test - Revised (HVLT-R)

  17. Neurocognitive function: visual attention and task switching [ Time Frame: From enrollment to 12 months ]
    Trail Making Test Part A and B (TMT)

  18. Neurocognitive function: verbal fluency [ Time Frame: From enrollment to 12 months ]
    Controlled Word Association Test (COWAT)

  19. Neurocognitive function: cognitive impairment [ Time Frame: From enrollment to 12 months ]
    Mini Mental Status Examination (MMSE)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Participants must have a biopsy proven solid malignancy and at least one intracranial measurable lesion spanning ≥5mm in maximal unidimensional size and radiographically consistent with or pathologically proven to be a brain metastasis AND meet one of the following additional criteria regarding the primary site or nature of the intracranial disease:

    • Melanoma with intracranial growth consistent with tumor progression despite immunotherapy
    • Gastrointestinal primary
    • HER2 positive breast cancer (subtype assessed using most representative tissue available in opinion of enrolling clinician and/or study PI)
    • Cystic metastases
    • Metastases ≥2cm in maximal unidimensional size
    • Locally recurrent metastases after prior stereotactic radiation
    • Locally recurrent metastases after prior whole brain radiation *Patients with metastases from melanoma, GI primaries, or HER2+ breast cancer, as well as those with cystic metastases or metastases ≥2cm in maximal unidimensional size, who have local recurrences after prior brain-directed radiation can only be treated in the strata permitting prior radiation (last two strata above)
  • Age ≥18 years at diagnosis of brain metastases
  • Estimated glomerular filtration rate of ≥ 60 mL/min/1.73m2
  • Karnofsky performance status of at least 70 (i.e. at minimum, "cares for self" but "unable to carry on normal activity or do active work")
  • Estimated survival based on extracranial disease of at least 3 months in the opinion of the enrolling clinician and/or study PI
  • Ability to understand and the willingness to sign a written informed consent document
  • The effects of AGuIX on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of the therapeutic component of study participation

Exclusion Criteria:

  • Participants who cannot undergo a brain MRI
  • Participants who cannot receive gadolinium
  • Participants with widespread, definitive leptomeningeal disease
  • Patients requiring radiation to either >10 targets (if naïve to whole brain radiation) or >20 targets (if whole brain radiation has been given previously) per the discretion of the treating clinician and/or study PI
  • Pregnant women are excluded from this study because of the potential deleterious effects of gadolinium on the developing fetus. Because there is an unknown but potential risk for adverse events in nursing infants, women who are breastfeeding are not eligible for this study
  • In cohorts who have received prior brain-directed radiation, patients are not eligible for this study if they have active (at the time of protocol screening) brain metastases that require radiation that are in or within 1.0cm of the brainstem, eyes, optic nerves, or optic chiasm if the juxtaposed organ at risk (i.e. brainstem, eyes, optic nerves, or optic chiasm) has previously received either >6.0 Gy in a single fraction or, if prior radiation was fractionated, a cumulative dose in 2.0 Gy equivalents, using an alpha/beta ratio of 2, of >40.0 Gy. In addition, all patients who have had prior brain-directed radiation, regardless of technique/dose/fractionation, are not eligible for the study until written approval is provided by the study/site PI

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): NCT04899908


Contacts
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Contact: Ayal Aizer, MD, MHS (617) 732-7560 aaaizer@partners.org

Locations
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United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Contact: Ayal Aizer    617-732-7560    aaaizer@partners.org   
Principal Investigator: Ayal Aizer, MD, MHS         
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Contact: Ayal Aizer, MD, MPH    617-732-7560    aaaizer@partners.org   
Principal Investigator: Ayal Aizer, MD, MPH         
Sponsors and Collaborators
Dana-Farber Cancer Institute
NH TherAguix SAS
Investigators
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Principal Investigator: Ayal Aizer, MD, MHS Brigham and Women's Hospital
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Responsible Party: Ayal Aizer, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT04899908    
Other Study ID Numbers: 20-240
First Posted: May 25, 2021    Key Record Dates
Last Update Posted: May 25, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data can be shared no earlier than 1 year following the date of publication
Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ayal Aizer, MD, Dana-Farber Cancer Institute:
AGuIX
Brain Cancer
Brain Metastases
Melanoma
Lung Cancer
Breast Cancer
HER2-positive Breast Cancer
Colorectal Cancer
Gastrointestinal Cancer
SRS
SRT
Whole brain radiation
Stereotactic Radiation
Nanoparticle
Cystic
Brain Tumor
Additional relevant MeSH terms:
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Breast Neoplasms
Colorectal Neoplasms
Melanoma
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Gastrointestinal Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Intestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases