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

NCT04789486 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 19-826
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer; Advanced Pancreatic Adenocarcinoma; Unresectable Pancreatic Cancer; Ductal Adenocarcinoma of the Pancreas

Keywords

Non-small Cell Lung Cancer; Advanced Pancreatic Adenocarcinoma; Unresectable Pancreatic Cancer; Ductal Adenocarcinoma of the Pancreas

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) Phase 1

  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

  3 months

• Compare Local Control at 12 months of Maximum tolerated dose MTD - Phase 2

  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

  12 months

Secondary Outcomes (10)

• Progression-free survival (PFS) at Maximum tolerated dose (MTD)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Overall Response Rate (ORR) at Maximum tolerated dose (MTD)

  Enrollment through study completion, an average of 1 year

• Serious Adverse Events at 90 Days

  90 days

• Serious Adverse Events at 12 months

  12 months

• Tumor Changes

  Enrollment through study completion, an average of 1 year

Study Arms (3)

AGUIX + SMART Phase 1

EXPERIMENTAL

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.

Drug: AGuIX; Radiation: Radiotherapy

AGUIX + SMART Phase 2

EXPERIMENTAL

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).

Drug: AGuIX; Radiation: Radiotherapy

SMART Phase 2

EXPERIMENTAL

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

Radiation: Radiotherapy

Interventions

AGuIX DRUG

Injected gadolinium-based nanoparticles

AGUIX + SMART Phase 1; AGUIX + SMART Phase 2

Radiotherapy RADIATION

Stereotactic magnetic resonance-guided adaptive radiation therapy

AGUIX + SMART Phase 1; AGUIX + SMART Phase 2; SMART Phase 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients should have clinical, radiographical, cytological, or histological confirmation of NSCLC or lung or nodal metastases from another primary cancer defined as within or touching the zone of the proximal bronchial tree, defined as a volume 2 cm in all directions around the trachea and proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus right and left lower lobe bronchi). Tumors that are immediately adjacent (\<1 cm) to mediastinal or pericardial pleura or other radiation-sensitive organs such as the esophagus and brachial plexus also are considered central tumors and are eligible for this protocol.
• OR Histologically or cytologically confirmed pancreatic ductal adenocarcinoma of the pancreatic head, body or tail.
• Participants must have measurable disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease.
• Eligible NSCLC patients must have no evidence of nodal involvement (N0), and disease has to be determined unresectable by a thoracic oncologist or the patient is medically inoperable.
• Locally advanced, unresectable pancreatic cancer as determined by a pancreaticobiliary surgeon as part of a multidisciplinary discussion at the investigative site, including multi-phasic CT demonstrating tumor abutment of the SMA or celiac axis, SMV or PV involvement which is not resectable without vascular reconstruction.
• Completion of at least 3 months of standard induction chemotherapy for LAPC, which should consist of either FOLFIRINOX, gemcitabine and nab-paclitaxel, or another standard combination of induction chemotherapy agent, with a washout period no longer than 10 weeks prior to first dose of study drug.
• No evidence of distant metastasis.
• Pancreatic or central NSCLC size ≤ 5cm.
• Age 18 years or older.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
• Ability to understand and follow the breathing instructions involved in the respiratory gating procedure.
• Participants must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• total bilirubin within normal institutional limits

You may not qualify if:

• Participants who have had prior radiation therapy to the chest or abdomen that would overlap with the current treatment field.
• Participants who are receiving any other investigational agents.
• Participants with known metastatic disease.
• History of allergic reactions attributed to gadolinium-based IV contrast.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because AGuIX is contrast agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AGuIX, breastfeeding should be discontinued if the mother is treated with AGuIX.
• Severe claustrophobia or anxiety.
• Known HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AGuIX. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
• Active duodenal or gastric ulcer disease or evidence of tumor invasion of the bowel or stomach based on endoscopy.
• Presence of a duodenal stent.
• Unable to undergo magnetic resonance imaging (MRI) due to any of the following:
• Presence of MRI-incompatible metal material or devices in the human body
• MRI-incompatible Pacemaker or defibrillator
• Insulin pump
• Aneurysm clip

Sponsors & Collaborators

• TherAguix S.A.: collaborator
• Dana-Farber Cancer Institute: lead

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

AGuIX; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Jonathan Leeman, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jonathan Leeman, MD

CONTACT

(617) 732-6452; jonathe_leeman@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 3, 2021
• First Posted: March 9, 2021
• Study Start: May 27, 2021
• Primary Completion (Estimated): April 10, 2028
• Study Completion (Estimated): September 10, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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

Locations

US (2)