Hypoxia Imaging for Esophageal Cancer to Guide Personalized Radiation Therapy (PIONEER)

May 15, 2026 updated by: University of Utah

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute
        • Contact:
        • Principal Investigator:
          • Shane Lloyd, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment: all patients
Drug: FMISO PET CT
Prior to the start of study therapy, eligible subjects will receive a FMISO-PET scan. If there is uptake visualized on the scan, the tumor will be considered as hypoxic. If there is no uptake seen on the FMISO-PET scan, tumors will be labeled not hypoxic.
Radiation: Radiation
Prior to the start of study therapy, eligible subjects will receive a FMISO-PET scan. If there is uptake visualized on the scan, the tumor will be considered as hypoxic. If there is no uptake seen on the FMISO-PET scan, tumors will be labeled not hypoxic. Subjects with tumors identified by imaging as hypoxic will be treated with a higher dose of radiation therapy. Tumors will be defined as being hypoxic if FMISO accumulation occurs as demonstrated by standardized uptake value (SUV) uptake in the tumor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
rate of grade ≥ 4 esophageal adverse events attributed to radiation therapy that occur within 30 days of finishing radiation therapy
Time Frame: 30 days after last study therapy
assess the safety and tolerability of using hypoxia PET/CT imaging with Fluorine-18 fluoromisonidazole (FMISO) and MRI measures of radioresistance to personalize radiation therapy by delivering a higher dose of radiation to hypoxic tumors
30 days after last study therapy
rate of grade ≥ 4 esophageal adverse events attributed to radiation therapy that occur within 84 days of finishing radiation therapy
Time Frame: 84 days after last study therapy
assess the safety and tolerability of using hypoxia PET/CT imaging with Fluorine-18 fluoromisonidazole (FMISO) and MRI measures of radioresistance to personalize radiation therapy by delivering a higher dose of radiation to hypoxic tumors
84 days after last study therapy
frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NIH CTCAE, version 5.0), seriousness, duration, and relationship to study treatment
Time Frame: 84 days after last study therapy
assess the safety and tolerability of using hypoxia PET/CT imaging with Fluorine-18 fluoromisonidazole (FMISO) and MRI measures of radioresistance to personalize radiation therapy by delivering a higher dose of radiation to hypoxic tumors
84 days after last study therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: Time from study therapy initiation to the time documented disease progression (as assessed by RECIST 1.1) or death from any cause for up to 18 months after last dose of study therapy
assess the efficacy of hypoxia imaging-guided radiation treatment
Time from study therapy initiation to the time documented disease progression (as assessed by RECIST 1.1) or death from any cause for up to 18 months after last dose of study therapy
Pathological complete response (pCR) rate
Time Frame: Long term follow up to occur for up to 18 months after last dose of study therapy.
assess the efficacy of hypoxia imaging-guided radiation treatment
Long term follow up to occur for up to 18 months after last dose of study therapy.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Utah

Collaborators

Huntsman Cancer Institute

Investigators

  • Principal Investigator: Shane Lloyd, MD, Huntsman Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 12, 2021

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

October 1, 2027

Study Registration Dates

First Submitted

April 12, 2021

First Submitted That Met QC Criteria

April 14, 2021

First Posted (Actual)

April 15, 2021

Study Record Updates

Last Update Posted (Actual)

May 19, 2026

Last Update Submitted That Met QC Criteria

May 15, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HCI137650

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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