Hypoxia-Guided Radiation for Esophageal Cancer

(PIONEER Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Randa Tao

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Utah

Disqualifiers: Severe claustrophobia, Metallic implants, HIV, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the treatment FMISO PET CT for esophageal cancer?

Research on head and neck cancers shows that FMISO PET CT can help identify areas of low oxygen (hypoxia) in tumors, which are often more resistant to treatment. This imaging technique can guide more targeted radiation therapy, potentially improving treatment outcomes. ^{1 2 3 4 5}

Is FMISO PET CT safe for use in humans?

The studies on FMISO PET CT, primarily used for imaging in head and neck cancers, indicate that it is a non-invasive technique, suggesting it is generally safe for human use. However, specific safety data for its use in esophageal cancer is not provided in the available research. ^{1 2 5 6 7}

What makes the FMISO PET CT treatment unique for esophageal cancer?

FMISO PET CT is unique because it uses a special imaging technique to identify areas of low oxygen (hypoxia) within tumors, which can help guide more precise radiation therapy. This approach is non-invasive and allows for targeted treatment adjustments based on the specific oxygen levels in the tumor, potentially improving the effectiveness of radiation therapy. ^{1 2 3 5 6}

Eligibility Criteria

This trial is for adults with esophageal cancer who can undergo chemoradiation therapy (CRT). They should be able to consent, have an ECOG Performance Status ≤ 2, and may include Stage IV patients with limited metastases if CRT is advised. Women must not be pregnant or must be post-menopausal.

Inclusion Criteria

I am eligible for initial or main treatment before surgery for esophageal cancer.

My cancer is stage IV, but it hasn't spread much and my team recommends CRT.

My side effects from previous treatments are mild or back to normal.

Exclusion Criteria

I have another cancer, but it won't affect this treatment's safety or results.

I do not have any severe illnesses that would prevent me from receiving chemoradiation.

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

All patients receive a baseline FMISO-PET and MRI to identify levels of hypoxia

1 week

1 visit (in-person)

Radiation Therapy

Patients with tumor hypoxia receive a higher dose of radiation therapy; others receive standard-of-care radiation

10 fractions

10 visits (in-person)

Interim MRI and Optional Boost

An additional MRI is performed after fraction 10; optional boost radiation dose if little or no response

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Treatment Details

Interventions

• FMISO PET CT (Radiosensitizer)

Trial Overview The trial tests personalized radiation therapy guided by hypoxia levels in tumors identified using FMISO PET CT and MRI scans. Patients with hypoxic tumors will receive higher radiation doses while others follow standard care. An interim MRI determines further treatment adjustments.

Participant Groups

Group I: Treatment: all patients Experimental Treatment 2 Interventions

FMISO PET CT is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as 18F-Fluoromisonidazole PET CT for:

• Diagnostic imaging for tumor hypoxia in various cancers, including esophageal cancer

🇪🇺 Approved in European Union as 18F-Fluoromisonidazole PET CT for:

• Diagnostic imaging for tumor hypoxia in various cancers, including head and neck cancers, gliomas, and non-small cell lung cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Huntsman Cancer Institute Salt Lake City, UT

Who Is Running the Clinical Trial?

University of Utah Lead Sponsor

References

1. Germany pubmed.ncbi.nlm.nih.gov

Hypoxia imaging with [18F]-FMISO-PET for guided dose escalation with intensity-modulated radiotherapy in head-and-neck cancers. [2021] Positron emission tomography (PET) with [(18)F]-fluoromisonidazole ([(18)F]-FMISO) provides a non-invasive assessment of hypoxia. The aim of this study is to assess the feasibility of a dose escalation with volumetric modulated arc therapy (VMAT) guided by [(18)F]-FMISO-PET for head-and-neck cancers (HNC).

2. United States pubmed.ncbi.nlm.nih.gov

Reproducibility of intratumor distribution of (18)F-fluoromisonidazole in head and neck cancer. [2021] Hypoxia is one of the main causes of the failure to achieve local control using radiotherapy. This is due to the increased radioresistance of hypoxic cells. (18)F-fluoromisonidazole ((18)F-FMISO) positron emission tomography (PET) is a noninvasive imaging technique that can assist in the identification of intratumor regions of hypoxia. The aim of this study was to evaluate the reproducibility of (18)F-FMISO intratumor distribution using two pretreatment PET scans.

3. Germany pubmed.ncbi.nlm.nih.gov

Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent. [2018] The purpose of the study was to evaluate [(18)F]fluoromisonidazole (FMISO) PET in advanced head and neck cancer during hypoxia-targeting therapy.

4. United States pubmed.ncbi.nlm.nih.gov

Tumor hypoxia imaging with [F-18] fluoromisonidazole positron emission tomography in head and neck cancer. [2022] Advanced head and neck cancer shows hypoxia that results in biological changes to make the tumor cells more aggressive and less responsive to treatment resulting in poor survival. [F-18] fluoromisonidazole (FMISO) positron emission tomography (PET) has the ability to noninvasively quantify regional hypoxia. We investigated the prognostic effect of pretherapy FMISO-PET on survival in head and neck cancer.

5. Germany pubmed.ncbi.nlm.nih.gov

Potential of [18F]-fluoromisonidazole positron-emission tomography for radiotherapy planning in head and neck squamous cell carcinomas. [2021] Positron-emission tomography (PET) with [(18)F]-fluoromisonidazole (FMISO) permits consideration of radiotherapy dose escalation to hypoxic volumes in head and neck cancers (HNC). However, the definition of FMISO volumes remains problematic. The aims of this study are to confirm that delayed acquisition at 4 h is most appropriate for FMISO-PET imaging and to assess different methods of volume segmentation.

6. Germany pubmed.ncbi.nlm.nih.gov

FMISO as a Biomarker for Clinical Radiation Oncology. [2017] Tumour hypoxia is a well-known negative prognostic marker in almost all solid tumours. [18F]Fluoromisonidazole (FMISO)-positron emission tomography (PET) is a non-invasive method to detect tumour hypoxia. Compared to other methods of hypoxia assessment it possesses some considerable advantages: It is non-invasive, it delivers spatial information on the hypoxia distribution within the entire tumour volume, and it can be repeated during the course of radio(chemo)therapy. This chapter briefly describes different methods of hypoxia evaluation and focuses on hypoxia PET imaging, with the most commonly used tracer being FMISO. The preclinical rationale and clinical studies to use FMISO-PET for patient stratification in radiation therapy are discussed as well as possible agents or radiation-dose modifications to overcome hypoxia.

7. Germany pubmed.ncbi.nlm.nih.gov

Two or four hour [¹⁸F]FMISO-PET in HNSCC. When is the contrast best? [2019] [¹⁸F]Fluoromisonidazole positron emission tomography (FMISO-PET) is a non invasive imaging technique that can assist detecting intra tumour regions of hypoxia. FMISO-PET evinces comparatively low signal-to-noise-ratio (SNR) and may be acquired dynamically or after different uptake times post injection (p.i.). The aim of this study was to identify, if static images acquired two hours (MISO2) or four hours (MISO4) p.i. reveal higher contrast.