Hypoxia-Guided Radiation for Esophageal Cancer

(PIONEER Trial)

Overseen By Rachel Kingsford

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Utah

Disqualifiers: Severe claustrophobia, Metallic implants, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering radiation therapy for esophageal cancer by assessing tumor oxygen levels. Patients will undergo FMISO PET CT scans to determine if their tumors have low oxygen levels. Those with low oxygen tumors will receive a higher radiation dose, while others will receive the standard treatment. The trial seeks participants with esophageal cancer who are eligible for chemoradiation therapy and comfortable with MRI scans. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to experience this innovative approach.

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 prior data suggests that this personalized radiation therapy protocol is safe for esophageal cancer patients?

Research has shown that using FMISO PET CT to guide radiation therapy is under study for its safety. This method helps doctors assess the oxygen levels in a tumor. Tumors with lower oxygen levels might receive higher doses of radiation.

In studies involving head-and-neck cancer patients, FMISO PET CT has been used to evaluate tumor response to treatment. Although these studies focused on different cancer types, they suggest that FMISO PET CT can be safe when combined with radiation therapy. Patients in these studies tolerated the treatment without major safety issues.

Since this trial is in an early phase, the primary goal is to assess safety. Early-phase trials often involve evaluating side effects and patient tolerance. So far, evidence indicates that FMISO PET CT with radiation therapy is well-tolerated, but further research is needed to confirm this for esophageal cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for esophageal cancer involve chemotherapy and radiation that target rapidly dividing cancer cells but can also affect healthy tissue. However, the treatment under study, FMISO PET CT, is unique because it uses advanced imaging to identify areas of low oxygen, or hypoxia, within the tumor. This allows radiation to be precisely targeted to these resistant areas, potentially improving effectiveness while minimizing damage to healthy cells. Researchers are excited about this approach because it offers a more personalized treatment strategy, which could lead to better outcomes and fewer side effects for patients with esophageal cancer.

What evidence suggests that this hypoxia-guided radiation technique is effective for esophageal cancer?

Studies have shown that FMISO-PET can identify areas in tumors with low oxygen levels, known as hypoxia. This information helps doctors deliver more precise radiation therapy. Research indicates that tumors with low oxygen might not respond well to standard radiation, so targeting these areas with a higher dose could enhance treatment effectiveness. Other studies have used FMISO to assess oxygen levels in various cancers and predict treatment outcomes. This method is promising because it targets the tumor more accurately based on its oxygen levels. Although more data is needed, early findings suggest that this approach could improve radiation therapy effectiveness for esophageal cancer. Participants in this trial will receive treatment guided by FMISO-PET to potentially enhance the precision and effectiveness of radiation therapy. ^{1 2 3 4 5}

Who Is on the Research Team?

Shane Lloyd

Principal Investigator

Huntsman Cancer Institute

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• FMISO PET CT

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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Published Research Related to This Trial

In a study of 20 head and neck cancer patients, (18)F-fluoromisonidazole ((18)F-FMISO) PET scans showed a strong correlation in intratumor hypoxia distribution in 71% of patients, indicating its potential for identifying hypoxic regions that contribute to radioresistance.

However, when focusing on specific hypoxic zones, only 46% of patients exhibited strong correlation, suggesting variability in (18)F-FMISO uptake and the need for further research to understand these changes before using single-time-point PET scans for hypoxia-targeted radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reproducibility of intratumor distribution of (18)F-fluoromisonidazole in head and neck cancer. Nehmeh, SA., Lee, NY., Schröder, H., et al.[2021]

In a study involving 15 patients with advanced head and neck cancer undergoing hypoxia-targeting therapy, FMISO PET imaging revealed significant hypoxia at baseline, which is common in advanced disease and typically indicates a poorer prognosis.

After 4 weeks of treatment, there was a marked reduction in FMISO uptake, suggesting effective hypoxia-targeted therapy, and the long-term follow-up showed promising survival rates, with a 5-year overall survival of 50% and a low rate of locoregional failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent. Hicks, RJ., Rischin, D., Fisher, R., et al.[2018]

Delayed acquisition of FMISO-PET imaging at 4 hours post-injection provides the best contrast for assessing hypoxic volumes in head and neck cancers, based on a study involving 15 patients.

Different methods of volume segmentation for FMISO imaging (fixed threshold, adaptive threshold, and FLAB) resulted in significant discrepancies in hypoxic volume measurements, highlighting the need for careful selection of segmentation techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of [18F]-fluoromisonidazole positron-emission tomography for radiotherapy planning in head and neck squamous cell carcinomas. Henriques de Figueiredo, B., Merlin, T., de Clermont-Gallerande, H., et al.[2021]

Using [(18)F]-FMISO-PET to guide dose escalation in radiotherapy for head-and-neck cancers showed that increasing the dose to hypoxic areas is feasible and can improve tumor control probability (TCP) by an average of 18.1%.

The study involved 10 patients with inoperable stages III-IV head-and-neck cancers, and the results indicated that while the average dose to the parotid glands increased, the rise in normal tissue complication probability (NTCP) was minimal, suggesting a safe approach to enhancing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoxia imaging with [18F]-FMISO-PET for guided dose escalation with intensity-modulated radiotherapy in head-and-neck cancers. Henriques de Figueiredo, B., Zacharatou, C., Galland-Girodet, S., et al.[2021]

[18F]Fluoromisonidazole (FMISO)-PET is an effective non-invasive imaging technique for detecting tumor hypoxia, which is a negative prognostic factor in solid tumors, providing detailed spatial information about hypoxia distribution within tumors.

FMISO-PET can be used repeatedly during radio(chemo)therapy, allowing for patient stratification and potential adjustments in treatment strategies to address hypoxia-related challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FMISO as a Biomarker for Clinical Radiation Oncology. Zschaeck, S., Steinbach, J., Troost, EG.[2017]

In a study involving 23 head and neck cancer patients, [¹⁸F]Fluoromisonidazole positron emission tomography (FMISO-PET) showed that imaging at 4 hours post-injection provided significantly higher contrast for detecting tumor hypoxia compared to imaging at 2 hours.

The results suggest that acquiring FMISO-PET data 4 hours after injection is optimal for accurately defining hypoxic regions within tumors, which can be crucial for planning effective radiotherapy treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two or four hour [¹⁸F]FMISO-PET in HNSCC. When is the contrast best? Abolmaali, N., Haase, R., Koch, A., et al.[2019]

In a study of 73 patients with advanced head and neck cancer, significant hypoxia was found in 79% of cases, indicating that tumors may be more aggressive and less responsive to treatment due to low oxygen levels.

Pretherapy FMISO-PET imaging showed that the tumor-to-blood maximum ratio (T/Bmax) and hypoxic volume (HV) were strong independent predictors of survival, suggesting that FMISO uptake could be a valuable prognostic tool for assessing patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor hypoxia imaging with [F-18] fluoromisonidazole positron emission tomography in head and neck cancer. Rajendran, JG., Schwartz, DL., O'Sullivan, J., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04846309?draw=2&rank=1

Hypoxia Imaging for Esophageal Cancer to Guide ... This is a Phase I trial evaluating the safety of personalized radiation therapy based on levels of hypoxia identified on FMISO-PET and MRI.

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-08286

[18F]FMISO PET/CT/MRI Informed Radiation Therapy for ... [18F]FMISO is a tracer used to look at how much oxygen is in the tumor. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8303992/

18F-FMISO-PET Hypoxia Monitoring for Head-and-Neck ... Our study aimed at evaluating radiomics dynamics of 18F-FMISO-hypoxia imaging during chemo-radiotherapy (CRT) as predictors for treatment ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/49/supplement_1/113P.1

Assessment of hypoxia in esophageal carcinomas using 18F ... It has been shown that PET with 18F-fluoromisonidazole (FMISO) allows the visualization of hypoxia in a variety of tumors. PET-data about ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3266560/

The value of [18F]fluorodeoxyglucose-PET/CT in ... Staging. The prognosis for oesophageal cancer is poor and up to 50% of patients present with advanced disease with multiple sites of nodal involvement or ...