Neoplasms

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Neoplastic Processes

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Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

All Drugs and Chemicals

Chelating Agents

Patients receive a single intravenous injection of AGuIX on day 1. Then patients undergo a whole brain radiation therapy, 5 days a week in weeks 1-2. The first radiotherapy session will be performed 4 hours after AGuIX injection.

Five dose escalation cohorts : 15 mg/kg, 30mg/kg, 50mg/kg, 75mg/kg and 100 mg/kg

A single intravenous injection on day 1. Dose level 1: 15mg/kg; Dose level 2: 30mg/kg, Dose level 3: 50mg/kg; Dose level 4: 75mg/kg; Dose level 5: 100mg/kg

AGuIX

30Gy in 10 sessions of 3Gy (5 days a week in weeks 1-2); first session 4 hours after AGuIX injection.

whole brain radiation therapy

Camille VERRY, MD

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. AGuIX particles may increase the effectiveness of radiation therapy by making tumor cells more sensitive to radiation.

PURPOSE: This first-in-man Phase I trial will study the side effects and best dose of AGuIX when injected together with whole brain radiation therapy in treating patients with multiple brain metastases. The effectiveness of the combination of AGuIX and radiation therapy will be also assessed.

The present study will investigate the safety, tolerability and spectrum of side effects of AGuIX in combination with whole brain radiation therapy. As such, this study will characterize the dose limiting toxicities (DLT) and maximum tolerated dose (MTD) of in combination with whole brain radiation therapy in patients with multiple brain metastases.

On day 1, patients will receive a single intravenous injection of AGuIX. An MRI scan will be performed 2 hours after injection to visualize the distribution of AGuIX in brain metastases and surrounding healthy tissue, and to evaluate the contrast enhancement in brain metastases. Then patients will undergo a whole brain radiation therapy, starting 4 hours after AGuIX injection, up to completion of 2 weeks, 5 days a week of treatment (30Gy, 3Gy/fraction).

During the first 24h after injection, several blood draws will be also performed in order to assess the pharmacokinetic of AGuIX.

After completion of study treatment, patients will be followed periodically.

Patients will be enrolled in cohorts and will be treated at sequentially rising dose levels of AGuIX combined with whole brain radiation therapy. Three subjects will initially enter at each dose. If none of the three experiences a dose-limiting toxicity we will proceed to the next dose. If one of the three experiences that level of toxicity, we will accrue 3 more subjects at that dose. If at any time there are two or more dose-limiting toxicities (in the 3-6 subjects) on a given dose, we will drop down to a lower dose. Dose escalation will continue until the MTD of AGuIX and whole brain radiation therapy is established. The MTD will then be one dose below the DLT occurring in at least 1 out of 3 subjects (2 out of 6 patients).

Radiosensitization of Multiple Brain Metastases Using AGuIX Gadolinium Based Nanoparticles

Etude Clinique de Phase I de Radiosensibilisation de métastases cérébrales Par Nanoparticules de Gadolinium

To determine Maximum-tolerated dose (MTD) of polysiloxane gadolinium-chelates based nanoparticles (AGuIX) given concurrently to the whole brain radiation therapy, according to incidence of dose limiting toxicity (DLT) graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

Measure of the T1 contrast enhancement in brain metastases and surrounding healthy tissue after intravenous administration of AGuIX particles

The intracranial progression-free survival will be assessed by MRI (1,3, 6, 9 and 12 months from the date of discovery of the metastases)

The overall survival will be assessed starting from the date of discovery of the metastases

NH TherAguix SAS

University Hospital, Grenoble

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.

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

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.

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.

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

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

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).

Distant Brain failure is defined as the presence of new brain metastases or leptomeningeal enhancement outside the irradiated volume.

The event of interest will be the local progression on any irradiated lesion.

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 will be analysed using volumetric T1 post-gadolinium MRI.

The assessment of safety will be based mainly on the frequency of adverse events based on the common toxicity criteria (CTCAE-V5.0) grade.

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.

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.

Centre Leon Berard

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Adenocarcinoma

Pancreatic Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gastrointestinal Agents

Pancrelipase

Pancreatin

Dose escalation of Activation and Guidance of Irradiation X (AGUIX) and SMART, magnetic resonance imaging (MR)-guided stereotactic body radiation therapy (SBRT).

Central lung tumor cohort will receive:

* five fractions of stereotactic body radiation therapy (SBRT)
* AGuIX Nanoparticle given on -7 or -14 day prior to radiation treatment, then with 1st fraction of radiation and for patients receiving radiation over a two (2) week period with the 4th fraction of radiation .

Locally advanced/unresectable pancreatic ductal adenocarcinoma-LAPC cohort, will receive:

five fractions of stereotactic body radiation therapy (SBRT)

* AGuIX Nanoparticle given on -7 or -14 day prior to radiation treatment, then with 1st fraction of radiation.

Randomized participants will receive recommended phase 1 dose established for their disease group (central lung tumor or locally advanced/unresectable pancreatic ductal adenocarcinoma-LAPC) of Activation and Guidance of Irradiation X (AGUIX) and SMART, magnetic resonance imaging (MR)-guided stereotactic body radiation therapy (SBRT).

Randomized participants will receive standard of care SMART, magnetic resonance imaging (MR)-guided stereotactic body radiation therapy (SBRT).

Stereotactic magnetic resonance-guided adaptive radiation therapy

Radiotherapy

Jonathan Leeman, MD

This research study is being done to help determine the safety and efficacy of gadolinium based nanoparticle, Activation and Guidance of Irradiation X (AGuIX), used in conjunction with MR-guided stereotactic body radiation therapy (SBRT) in the treatment of pancreatic cancer and lung tumors.

This is a seamless phase I/II trial with two separate disease groups/cohorts (centrally located lung tumors and locally advanced/unresectable pancreatic ductal adenocarcinoma-LAPC). The Phase I part is determining for each disease group a safe dose-level that will be evaluated in the Phase II component of the study. The phase II part of the study is a randomized controlled trial that tests, for each disease group, the treatment efficacy of stereotactic body radiation therapy (SBRT) in combination with AGuIX gadolinium-chelated polysiloxane based nanoparticles compared to treatment with stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) alone

The U.S. Food and Drug Administration (FDA) has not approved Activation and Guidance of Irradiation X (AGuIX) as a treatment for any disease.

AGuIX is a gadolinium-based nanoparticle, gadolinium is the drug used for an MR with contrast. It is believed that the AGuIX may help the radiation received work better by making a tumor more sensitive to the radiation and allowing doctors to see the tumor more clearly. AGuIX has been tested in one previous study with humans. It was found that AGuIX did make tumor cells more sensitive to radiation therapy.

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

Participants will receive study treatment for 5 treatment days and will be followed for a year after your treatment ends.

It is expected that about 100 people will take part in this research study.

Nano-SMART: Nanoparticles With MR Guided SBRT in Centrally Located Lung Tumors and Pancreatic Cancer

Nano-SMART: An Adaptive Phase I-II Trial of AGuIX Gadolinium-based Nanoparticles With Stereotactic Magnetic Resonance-guided Adaptive Radiation Therapy for Centrally Located Lung Tumors and Locally Advanced Unresectable Pancreatic Ductal Adenocarcinoma

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.

Evaluated by the occurrence of Dose Limiting Toxicity (DLT) over the duration of the study using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Evaluate SMART + AGuIX local control at 12 months compared to SMART alone. Local control at 12 months is defined as the treated tumor is equal to or less than the tumor volume at start of SMART. Progression would be defined per RECIST criteria

NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be used.

Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.

Bayesian hierarchical two-sample test for binary outcomes

Described using descriptive statistics and longitudinal analyses

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Radiosensitization of Multiple Brain Metastases Using AGuIX Gadolinium Based Nanoparticles	NCT02820454	Brain Metastase...	AGuIX whole brain rad...	18 Years -	University Hospital, Grenoble
Evaluating AGuIX® Nanoparticles in Combination With Stereotactic Radiation for Brain Metastases	NCT04094077	Brain Metastase...	AGuIX	18 Years -	Centre Leon Berard
Nano-SMART: Nanoparticles With MR Guided SBRT in Centrally Located Lung Tumors and Pancreatic Cancer	NCT04789486	Non-small Cell ... Advanced Pancre... Unresectable Pa... Ductal Adenocar...	AGuIX Radiotherapy	18 Years -	Dana-Farber Cancer Institute
Nano-SMART: Nanoparticles With MR Guided SBRT in Centrally Located Lung Tumors and Pancreatic Cancer	NCT04789486	Non-small Cell ... Advanced Pancre... Unresectable Pa... Ductal Adenocar...	AGuIX Radiotherapy	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for aguix

Every month we try and update this database with for aguix cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for aguix

Every month we try and update this database with for aguix cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for aguix cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.