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

Primary Purpose

Esophageal Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Radiation
FMISO PET CT
Sponsored by
University of Utah
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Note: Stage IV patients with limited metastatic disease burden may be eligible if CRT is recommended by the multidisciplinary team.

  • 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).

Sites / Locations

  • Huntsman Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment: all patients

Arm Description

Outcomes

Primary Outcome Measures

rate of grade ≥ 4 esophageal adverse events attributed to radiation therapy that occur within 30 days of finishing radiation 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
rate of grade ≥ 4 esophageal adverse events attributed to radiation therapy that occur within 84 days of finishing radiation 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
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
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

Secondary Outcome Measures

Progression-free survival (PFS)
assess the efficacy of hypoxia imaging-guided radiation treatment
Pathological complete response (pCR) rate
assess the efficacy of hypoxia imaging-guided radiation treatment

Full Information

First Posted
April 12, 2021
Last Updated
June 12, 2023
Sponsor
University of Utah
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1. Study Identification

Unique Protocol Identification Number
NCT04846309
Brief Title
Hypoxia Imaging for Esophageal Cancer to Guide Personalized Radiation Therapy
Acronym
PIONEER
Official Title
Hypoxia Imaging for Esophageal Cancer to Guide Personalized Radiation Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 12, 2021 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
April 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Utah

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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 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 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment: all patients
Arm Type
Experimental
Intervention Type
Radiation
Intervention Name(s)
Radiation
Intervention Description
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 SUV uptake in the tumor.
Intervention Type
Drug
Intervention Name(s)
FMISO PET CT
Intervention Description
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.
Primary Outcome Measure Information:
Title
rate of grade ≥ 4 esophageal adverse events attributed to radiation therapy that occur within 30 days of finishing radiation therapy
Description
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
Time Frame
30 days after last study therapy
Title
rate of grade ≥ 4 esophageal adverse events attributed to radiation therapy that occur within 84 days of finishing radiation therapy
Description
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
Time Frame
84 days after last study therapy
Title
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
Description
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
Time Frame
84 days after last study therapy
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
assess the efficacy of hypoxia imaging-guided radiation treatment
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
Title
Pathological complete response (pCR) rate
Description
assess the efficacy of hypoxia imaging-guided radiation treatment
Time Frame
Long term follow up to occur for up to 18 months after last dose of study therapy.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female subject aged ≥ 18 years. Esophageal cancer patient eligible to undergo either neoadjuvant or definitive CRT. Note: Stage IV patients with limited metastatic disease burden may be eligible if CRT is recommended by the multidisciplinary team. 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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rachel Kingsford
Phone
801-585-0115
Email
rachel.kingsford@hci.utah.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Randa Tao, MD
Organizational Affiliation
Huntsman Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rachel Kingsford
Phone
801-585-0115
Email
rachel.kingsford@hci.utah.edu
First Name & Middle Initial & Last Name & Degree
Randa Tao, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Hypoxia Imaging for Esophageal Cancer to Guide Personalized Radiation Therapy

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