Overview

This is a Phase I trial evaluating the safety of personalized radiation therapy based on levels of hypoxia identified on FMISO-PET and MRI. All patients will receive a baseline FMISO positron emission tomography (PET) and MRI to identify levels of hypoxia. Patients with tumor hypoxia will receive a higher dose of radiation therapy. Subjects who do not have hypoxic tumors will be treated with the standard-of-care radiation regimen. After fraction 10 of radiation therapy, an additional MRI will be performed. If this interim MRI demonstrates little or no response (as defined in Section 6), an optional boost radiation dose can be administered.

Trial enrollment will be conducted in two parts. In Part 1, eight patients will be enrolled. After all eight patients have completed the 30 day dose-limiting toxicity (DLT) period, enrollment will be placed on hold and safety will be evaluated. During the interim analysis, one additional patient will be allowed to be enrolled in the trial. If the trial meets stopping rules as described in Section 11.3, the trial will be re-evaluated by the Data and Safety Monitoring Committee (DSMC) and the Principal Investigator. However, if the rate of DLTs remains below the unacceptable toxicity rate, enrollment will open to the enrollment of eight more patients.

Eligibility

Inclusion Criteria:

• Male or female subject aged ≥ 18 years.
• Esophageal cancer patient eligible to undergo either neoadjuvant or definitive chemoradiation therapy (CRT).

        Note: Stage IV patients with limited metastatic disease burden may be eligible if CRT is
        recommended by the multidisciplinary team.
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
          -  For female subjects: Negative pregnancy test or evidence of post-menopausal status.
             The post-menopausal status will be defined as having been amenorrheic for 12 months
             without an alternative medical cause. The following age-specific requirements apply:
               -  Women < 50 years of age:
                    -  Amenorrheic for ≥ 12 months following cessation of exogenous hormonal
                       treatments; and
                    -  Luteinizing hormone and follicle-stimulating hormone levels in the
                       post-menopausal range for the institution; or
                    -  Underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
               -  Women ≥ 50 years of age:
                    -  Amenorrheic for 12 months or more following cessation of all exogenous
                       hormonal treatments; or
                    -  Had radiation-induced menopause with last menses >1 year ago; or
                    -  Had chemotherapy-induced menopause with last menses >1 year ago; or
                    -  Underwent surgical sterilization (bilateral oophorectomy, bilateral
                       salpingectomy, or hysterectomy).
          -  Recovery to baseline or ≤ Grade 2 CTCAE v5 from toxicities related to any prior
             treatments, unless AE(s) are clinically non-significant and/or stable on supportive
             therapy.
          -  Able to provide informed consent and willing to sign an approved consent form that
             conforms to federal and institutional guidelines.
        Exclusion Criteria:
          -  Unable to undergo an MRI for any reason, including:
               -  Severe claustrophobia not amenable to pre-medication
               -  Presence of metallic objects or implanted medical devices in the body that are
                  not MRI-compatible (e.g., non-MRI-compatible cardiac pacemaker, deep brain
                  stimulator, neurostimulator, aneurysm clips, surgical clips, prostheses,
                  artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos
                  near the eye, or steel implants)
          -  Patients with a prior or concurrent malignancy whose natural history or treatment does
             not have the potential to interfere with the safety or efficacy assessment of the
             radiation therapy are eligible for this trial.
          -  The subject has severe, uncontrolled, significant intercurrent or recent illness that
             would exclude them from being a candidate for chemoradiation therapy.
             --Any other condition that would, in the Investigator's judgment, contraindicate the
             subject's participation in the clinical study due to safety concerns or compliance
             with clinical study procedures.
          -  Known HIV infection with a detectable viral load at the time of screening. Note:
             Patients on effective antiretroviral therapy or who will plan on going on
             antiretroviral therapy at the time of screening are eligible for this trial. HIV
             testing is not required for eligibility.
          -  Known prior severe hypersensitivity to gadolinium, FMISO or any component in its
             formulations (NCI CTCAE v5.0 Grade ≥ 3).