Adaptive Radiation Therapy for Anal Cancer

(MAESTRO Trial)

Recruiting at 3 trial locations

Overseen By Ali Hosni

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Disqualifiers: Previous chemotherapy, Previous RT, Others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: Varies based on risk group

80 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed study is a phase II, single arm, open-label trial of MR-guided radiation therapy (RT) with risk stratified RT dose selection in patients with anal cancer. Based on previous data, a risk adaptive treatment approached is proposed in 4 groups: Low risk, standard risk, intermediate risk, and high risk. Human papillomavirus (HPV) DNA will be analyzed to identify novel biomarkers that predict chemoradiotherapy (CRT) response and toxicity.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment MR-Adaptive Radiation Therapy for anal cancer?

Research shows that MR-guided adaptive radiation therapy has been used effectively in other cancers, like prostate and cervical cancer, by allowing precise targeting and adaptation of treatment plans. This suggests it could also be beneficial for anal cancer by improving treatment accuracy and potentially reducing side effects. ^{1 2 3 4 5}

Is MR-guided adaptive radiation therapy safe for humans?

MR-guided adaptive radiation therapy (MRgRT) has been used successfully in adults for various conditions, showing potential for reducing side effects. It offers improved imaging without extra radiation exposure, which suggests it is generally safe for human use. ^{1 2 6 7 8}

What makes MR-Adaptive Radiation Therapy unique for treating anal cancer?

MR-Adaptive Radiation Therapy is unique because it uses real-time MRI imaging to precisely target the cancer, allowing for daily adjustments to the treatment plan based on changes in the tumor's size or position. This approach can potentially improve accuracy and reduce side effects compared to traditional radiation therapy. ^{1 2 3 4 9}

Eligibility Criteria

This trial is for adults over 18 with a confirmed diagnosis of anal squamous cell carcinoma, at clinical stage T1-4 N0-1 M0. They must be fit for definitive radiation or chemoradiation therapy and have an ECOG performance status of 0-2. Excluded are those who've had prior treatments for anal cancer, previous pelvic radiation that overlaps with this study's area, or other cancers unless they're low-risk and disease-free for two years.

Inclusion Criteria

I am eligible for targeted radiation or combined chemotherapy and radiation treatment.

My cancer is in an early or locally advanced stage but hasn't spread far.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I have had treatment for anal cancer before.

I have not had radiation therapy in the abdomino-pelvic area that overlaps with this study's area.

I've been cancer-free for 2 years, or I had certain skin or cervical cancers treated within 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo MR-guided radiation therapy with risk-stratified dose selection and chemotherapy cycles based on clinical and biological biomarkers

Varies based on risk group

Follow-up

Participants are monitored for safety and effectiveness after treatment, including completion of questionnaires and clinic visits

5 years

Treatment Details

Interventions

• MR-Adaptive Radiation Therapy

Trial Overview The study tests MR-guided radiation therapy in patients with anal cancer using a risk-adaptive approach to determine treatment doses across four groups: low, standard, intermediate, and high risk. It also aims to identify new biomarkers from HPV DNA that could predict how well patients respond to the treatment and their likelihood of experiencing side effects.

MR-Adaptive Radiation Therapy is already approved in European Union, United States for the following indications:

Approved in European Union as MR-Adaptive Radiation Therapy for:

• Anal cancer

Approved in United States as MR-Adaptive Radiation Therapy for:

• Anal cancer

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Medical College of Wisconsin Cancer Center, Allegheny Health Network, Austin Health

Collaborator

Trials

1

Recruited

80+

Medical College of Wisconsin

Collaborator

Trials

645

Recruited

1,180,000+

Findings from Research

The first clinical implementation of online adaptive magnetic resonance image-guided radiation therapy (MR-IGRT) was successfully conducted on 5 patients with abdominopelvic cancers, demonstrating the feasibility of real-time adaptive planning during treatment.

Out of 170 treatment fractions in an expanded cohort, 30.6% required online reoptimization, indicating that adapting treatment plans based on daily imaging can effectively address changes in tumor size and patient anatomy, enhancing treatment precision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Online Magnetic Resonance Image Guided Adaptive Radiation Therapy: First Clinical Applications. Acharya, S., Fischer-Valuck, BW., Kashani, R., et al.[2022]

In a phase 1 trial involving 22 prostate cancer patients, stereotactic MR-guided adaptive radiation therapy (SMART) demonstrated a low risk of acute urinary (22.7%) and gastrointestinal (4.5%) toxic effects, with no severe grade 3+ events reported.

Daily plan adaptation during SMART significantly improved dosimetry, ensuring that 100% of treatment plans were optimized to protect critical organs, highlighting the importance of real-time adjustments in radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance-Guided Prostate Stereotactic Body Radiation Therapy With Daily Online Plan Adaptation: Results of a Prospective Phase 1 Trial and Supplemental Cohort. Leeman, JE., Cagney, DN., Mak, RH., et al.[2022]

Magnetic resonance imaging (MRI)-guided adaptive radiotherapy enhances the precision of radiation treatment by providing real-time anatomical and functional imaging during therapy sessions.

This advanced imaging technique could lead to improved treatment outcomes by allowing for adjustments in radiation delivery based on the patient's changing anatomy throughout the course of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided adaptive radiotherapy: a solution to the future. Kupelian, P., Sonke, JJ.[2022]

Adaptive magnetic resonance-guided external beam radiation therapy (aMRgRT) can effectively be used as an alternative treatment for cervical cancer recurrence when traditional brachytherapy is impractical, as demonstrated in a case involving a 31-year-old patient.

aMRgRT offers advantages over standard x-ray imaging by providing daily MR imaging for better precision in treatment, allowing for adaptive adjustments based on the movements of organs at risk and target volumes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive Magnetic Resonance-Guided External Beam Radiation Therapy for Consolidation in Recurrent Cervical Cancer. Felici, F., Benkreira, M., Lambaudie, É., et al.[2022]

MRI is a crucial tool for assessing treatment response in anal cancer, helping to detect recurrence and evaluate complications related to both treatment and the tumor itself.

This review highlights the importance of imaging in managing anal cancer, emphasizing that MRI provides valuable insights that complement clinical evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Follow-up imaging of anal cancer after treatment. El Homsi, M., Sheedy, SP., Rauch, GM., et al.[2023]

A survey of 12 pediatric radiotherapy institutions indicated that while the expected benefit of magnetic resonance guided radiotherapy (MRgRT) for reducing toxicity and improving outcomes is modest, there is a significant potential for benefit in 55% of primary tumor scenarios and 62% of metastatic tumor scenarios.

The study highlights the need for further investigation into MRgRT's role in pediatric oncology, particularly through prospective studies or registration trials, to better understand its impact on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role of MR-guided adaptive radiotherapy in pediatric oncology: Results from a SIOPE-COG survey. Seravalli, E., Kroon, PS., Buatti, JM., et al.[2022]

MRI-guided radiotherapy (MRIgRT) has been effectively used in treating 642 patients over 4.5 years, with breast and gastrointestinal cancers being the most common indications, showcasing its broad applicability in radiation oncology.

Adaptive radiotherapy (ART) was utilized in 190 patients, with a significant 67.6% of treatment fractions being adapted, particularly for abdominal cancers, indicating the technology's ability to adjust treatment based on real-time anatomical changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance Image-Guided Radiotherapy (MRIgRT): A 4.5-Year Clinical Experience. Henke, LE., Contreras, JA., Green, OL., et al.[2023]

The development of an online Magnetic Resonance guided Radiation Therapy (MRgRT) system aims to enhance safety by providing real-time MRI images before radiation treatment, allowing for better image guidance.

A thorough failure modes and effects analysis identified potential risks during the design and operation of the MRgRT system, leading to design improvements and safety measures before installation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poster - Thur Eve - 05: Safety systems and failure modes and effects analysis for a magnetic resonance image guided radiation therapy system. Lamey, M., Carlone, M., Alasti, H., et al.[2019]

Image-guided radiotherapy (IGRT) combined with intensity-modulated radiotherapy (IMRT) is effective in reducing rectal and bladder toxicity during high-dose prostate cancer treatment, highlighting its safety and efficacy.

Adaptive radiotherapy, which involves replanning based on anatomical changes, is crucial for head and neck tumors, but these advanced techniques require careful validation due to their complexity and cost.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Image-guided and adaptive radiotherapy]. Louvel, G., Cazoulat, G., Chajon, E., et al.[2012]

References

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

Online Magnetic Resonance Image Guided Adaptive Radiation Therapy: First Clinical Applications. [2022]

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

Magnetic Resonance-Guided Prostate Stereotactic Body Radiation Therapy With Daily Online Plan Adaptation: Results of a Prospective Phase 1 Trial and Supplemental Cohort. [2022]

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

Magnetic resonance-guided adaptive radiotherapy: a solution to the future. [2022]

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

Adaptive Magnetic Resonance-Guided External Beam Radiation Therapy for Consolidation in Recurrent Cervical Cancer. [2022]

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

Follow-up imaging of anal cancer after treatment. [2023]

6. Ireland pubmed.ncbi.nlm.nih.gov

The potential role of MR-guided adaptive radiotherapy in pediatric oncology: Results from a SIOPE-COG survey. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Magnetic Resonance Image-Guided Radiotherapy (MRIgRT): A 4.5-Year Clinical Experience. [2023]

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

Poster - Thur Eve - 05: Safety systems and failure modes and effects analysis for a magnetic resonance image guided radiation therapy system. [2019]

9. France pubmed.ncbi.nlm.nih.gov

[Image-guided and adaptive radiotherapy]. [2012]