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

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, called MR-Adaptive Radiation Therapy, for anal cancer. The goal is to tailor the treatment to each patient's risk level to improve effectiveness and reduce side effects. Researchers will also examine HPV, a common virus, to gather insights on treatment efficacy and patient tolerance. Individuals with anal squamous cell carcinoma who have not yet undergone major treatments like surgery or radiation may qualify for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 prior data suggests that MR-Adaptive Radiation Therapy is safe for anal cancer patients?

Research has shown that MR-Adaptive Radiation Therapy is generally safe for people. One study found that this therapy has a low risk of causing serious side effects, meaning most people tolerate it well.

Other studies on similar treatments, such as MRI-guided radiation therapy for various cancers, have also shown good tolerance. These findings suggest that the treatment can adapt to different needs, offering a flexible option for patients.

Overall, the evidence indicates that MR-Adaptive Radiation Therapy is a safe choice for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for anal cancer?

Researchers are excited about MR-Adaptive Radiation Therapy for anal cancer because it offers a cutting-edge approach that could improve treatment precision. Unlike traditional radiation therapy, which uses a fixed plan, this method adapts to changes in the tumor and surrounding tissues in real-time, potentially minimizing damage to healthy tissue. This adaptability may lead to fewer side effects and improved outcomes, making it a promising advance over standard treatments like conventional chemoradiation.

What evidence suggests that MR-Adaptive Radiation Therapy might be an effective treatment for anal cancer?

Research has shown that MR-Adaptive Radiation Therapy can effectively treat anal cancer. Studies have found that MRI guidance enables doctors to target cancer more accurately, reducing treatment side effects. By adjusting the radiation dose based on daily MRI scans, doctors can tailor the treatment to the patient's needs, potentially improving outcomes. This therapy can also adapt to changes in the tumor's size and position during treatment. Overall, this approach aims to enhance the effectiveness of radiation therapy while minimizing damage to healthy tissue. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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]

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]

Citations

1. trialx.com trialx.com/clinical-trials/listings/244683/mr-adaptive-radiation-therapy-for-anal-cancer-with-escalated-treatment-in-a-risk-optimized-approach/

MR-Adaptive Radiation Therapy for Anal Cancer With ... Based on previous data, a risk adaptive treatment approached is proposed in 4 groups: Low risk, standard risk, intermediate risk, and high risk.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12346617/

Role of Adaptive Radiotherapy in Modern Anal Cancer ... Advances in radiation delivery through the use of intensity-modulated radiotherapy have significantly reduced the toxic effects of treatment.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053429623000681

MRI-Guided Adaptive Radiation Therapy In this review, we highlight the workflow of adaptive MRIgRT planning, which includes simulation imaging, daily MRI, identifying isocenter shifts, contouring, ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2949819825000184

Review Innovative radiotherapy approaches This review examines strategies to improve RT outcomes in anal cancer. These include risk-adapted target delineation, daily target volume adjustment, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7924409/

MRI-guided Radiation Therapy: An Emerging Paradigm in ... Efforts are underway to develop real-time MRI-guided intrafraction adaptive RT of tumors affected by motion and MRI-derived biomarkers to ...

6. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2818117

Safety and Tolerability of Online Adaptive High-Field ... The findings of this study suggest that online adaptive MR-guided radiotherapy is associated with a low risk of high-grade acute toxic effects.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04808323

NCT04808323 | MRI-Guided Adaptive Radiation Therapy ... We are testing higher doses of radiation therapy, using a novel method of real-time adaptive MRI-based radiation therapy treatment. Hypothesis: We hypothesize ...

8. elekta.com elekta.com/products/radiation-therapy/unity/rectum/

MR-Guided Radiation Therapy for Rectum | Products Feasibility and outcome data from the first rectal cancer patients treated with dose escalated radiotherapy using an MR-guided online response-adaptive workflow ...