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

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}

Research Team

Shane Lloyd

Principal Investigator

Huntsman Cancer Institute

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

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

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

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Findings from Research

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]

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]

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]

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]

[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]

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]

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

Reproducibility of intratumor distribution of (18)F-fluoromisonidazole in head and neck cancer. [2021]

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]

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

Tumor hypoxia imaging with [F-18] fluoromisonidazole positron emission tomography in head and neck cancer. [2022]

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]

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

FMISO as a Biomarker for Clinical Radiation Oncology. [2017]

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

Two or four hour [¹⁸F]FMISO-PET in HNSCC. When is the contrast best? [2019]