Overview

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.

Eligibility

Inclusion Criteria:

        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
               -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
               -  creatinine within normal institutional limits OR
          -  Creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above
             institutional normal.
          -  The effects of AGuIX on the developing human fetus are unknown. For this reason, as
             well as the known teratogenic effects of radiation, women of child-bearing potential
             and men must agree to use adequate contraception prior to study entry and for the
             duration of study participation.
          -  Ability to understand and the willingness to sign a written informed consent document.
        Exclusion Criteria:
          -  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:
               1. Presence of MRI-incompatible metal material or devices in the human body
               2. MRI-incompatible Pacemaker or defibrillator
               3. Insulin pump
               4. Aneurysm clip
               5. Artificial heart valve
               6. Cochlear implant
               7. Shrapnel or gunshot injury
               8. Cataract surgery with implant unsafe for MRI