Adaptive Radiation for Anal Cancer

Overseen By Christina Chesnakov

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Columbia University

Disqualifiers: Invasive malignancy, Prior chemotherapy, Recurrent disease, 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: 5

Duration: 6 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new method of using radiation therapy to treat advanced anal squamous cell cancer. By adjusting the radiation dose daily based on changes in the tumor and the patient's body, the researchers aim to better target the cancer while protecting nearby healthy organs. Participants will receive both chemotherapy and adaptive radiation therapy (Artificial Intelligence Guided Daily Radiotherapy Treatment Planning and Delivery). Individuals with a confirmed diagnosis of advanced anal cancer who have not received previous chemotherapy or radiation for it might be suitable for this study.

As an unphased trial, this study provides a unique opportunity to explore innovative treatment methods that could enhance future cancer care.

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 this adaptive radiation therapy is safe for treating anal cancer?

Research shows that artificial intelligence (AI) in radiation therapy can enhance treatment planning and delivery. This approach may target tumors more accurately while protecting healthy tissues. Although early studies have not focused on safety, they have demonstrated that AI-guided methods can create superior treatment plans compared to traditional methods.

AI-guided adaptive radiotherapy represents a new approach. It uses daily scans to adjust the radiation dose based on changes in the tumor and body, aiming to make treatment safer and more effective. While specific safety data is not yet available, the AI technology is designed to improve precision, potentially reducing side effects.

Currently, there are no reports of major safety concerns with AI-guided radiotherapy. However, as this is a pilot study, further research is necessary to fully understand its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores using artificial intelligence (AI) to guide daily radiotherapy treatment planning and delivery for anal cancer. Unlike traditional methods that rely on pre-set plans, AI can adapt the radiation treatment based on daily changes in the patient's anatomy, potentially increasing precision and effectiveness. This adaptive approach aims to maximize tumor targeting while minimizing damage to surrounding healthy tissues, offering a promising improvement over existing standard care.

What evidence suggests that Artificial Intelligence Guided Daily Radiotherapy Treatment Planning and Delivery is effective for anal cancer?

Research has shown that artificial intelligence (AI) in radiotherapy can customize treatments to fit each patient's body. In this trial, participants will receive AI-guided adaptive radiotherapy, allowing for daily adjustments based on shifts in the tumor or patient's body. Studies have found that AI can automatically plan and adjust radiation doses, potentially targeting tumors more precisely while protecting healthy tissue. Compared to current clinical practices, this method may improve treatment effectiveness. For anal cancer, this could lead to better tumor targeting and fewer side effects from radiation. ^{2 3 4 5 6}

Who Is on the Research Team?

Lisa Kachnic, MD

Principal Investigator

Principal Investigator

Are You a Good Fit for This Trial?

This trial is for adults with advanced anal squamous cell cancer, who are in good health otherwise and have not had prior treatments for this cancer. They must be able to perform daily activities without significant assistance (ECOG ≤2) and agree to use contraception during the study.

Inclusion Criteria

Agreement to use adequate contraception, understanding of informed consent document

Life expectancy of greater than 12 months

My cancer is a specific type of anal cancer.

Exclusion Criteria

I have had all of my tumor surgically removed.

Prior allergic reaction to 5-Fluorouracil or mitomycin C

Presence of artificial organ prosthetics, pacemakers or other implantable devices

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive concurrent chemotherapy and adaptive radiation treatment for anal cancer

6 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

Long-term follow-up

Participants are monitored for complete clinical response and long-term outcomes

6 months

What Are the Treatments Tested in This Trial?

Interventions

• 5-Fluorouracil
• Artificial Intelligence Guided Daily Radiotherapy Treatment Planning and Delivery
• Capecitabine
• Mitomycin-C

Trial Overview

The study tests a new approach using AI-guided radiation therapy tailored daily, combined with chemotherapy drugs like 5-Fluorouracil, Capecitabine, or Mitomycin-C. It aims to improve targeting of the tumor while protecting healthy tissue.

How Is the Trial Designed?

Group I: Chemotherapy and Adaptive Radiation Treatment Planning Experimental Treatment 4 Interventions

Subjects will receive concurrent chemotherapy and radiation as part of their treatment for anal cancer. Subjects will receive standard of care 54 Gy of radiation, 5 days a week for 6 weeks. In addition, subjects will receive standard of care chemotherapy, with mitomycin C (10mg/meters squared IV on Day 1) and 5-Fluorouracil (1000mg/meters squared via IV on days 1-4 and 29-32) or capecitabine (825 mg/meters squared in two divided doses by mouth on days of radiotherapy).

Artificial Intelligence Guided Daily Radiotherapy Treatment Planning and Delivery is already approved in European Union, United States for the following indications:

Approved in European Union as Adaptive Radiation Therapy for:

• Locally advanced anal squamous cell cancer

Approved in United States as Adaptive Radiation Therapy for:

• Locally advanced anal squamous cell cancer

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Varian

Collaborator

Trials

5

Recruited

380+

Varian Medical Systems

Industry Sponsor

Trials

63

Recruited

3,700+

Dow R. Wilson

Varian Medical Systems

Chief Executive Officer since 2012

MBA from Dartmouth's Amos Tuck School of Business, BA from Brigham Young University

Dr. Deepak Khuntia

Varian Medical Systems

Chief Medical Officer since 2020

MD from the University of Cambridge, PhD from the University of Leicester

Published Research Related to This Trial

The adaptive radiotherapy (ART) strategy maintained excellent target volume coverage (99.0%) compared to the non-adaptive approach (98.3%), indicating its efficacy in delivering precise treatment for rectal cancer.

ART significantly reduced radiation exposure to the small bowel and bladder during long treatment schedules, suggesting a safer option for patients by minimizing potential side effects, although the absolute differences were small.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric benefit of an adaptive treatment by means of plan selection for rectal cancer patients in both short and long course radiation therapy. de Jong, R., Visser, J., Crama, KF., et al.[2020]

Daily adaptive radiation therapy (ART) for non-small cell lung cancer (NSCLC) can effectively reduce lung exposure while maintaining adequate coverage of the tumor target volume, as shown in a study involving 13 patients and various treatment planning scenarios.

The study found that ART allows for dose escalation to the tumor without increasing the risk of damage to surrounding healthy tissues, suggesting a potential for improved local tumor control while minimizing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric benefits of adaptive radiation therapy for patients with stage III non-small cell lung cancer. Hoppen, L., Sarria, GR., Kwok, CS., et al.[2023]

The fully automated adaptive planning (AAP) method effectively compensates for anatomical changes in prostate cancer patients during radiation therapy, ensuring acceptable target coverage for most patients.

Compared to conventional planning methods, the AAP method significantly reduces radiation exposure to critical organs like the rectum and bladder, improving safety while maintaining effective treatment for the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A fully automated method for CT-on-rails-guided online adaptive planning for prostate cancer intensity modulated radiation therapy. Li, X., Quan, EM., Li, Y., et al.[2020]

Weekly and every-other-week online adaptive radiation therapy (ART) for cervical cancer significantly improves the sparing of organs-at-risk (OARs) compared to traditional image-guided radiation therapy (IGRT), while maintaining similar coverage of the clinical target volume (CTV).

In a study of 10 patients, weekly ART showed improvements in 15 out of 18 dose metrics evaluated, indicating that more frequent adaptations can effectively reduce radiation exposure to surrounding healthy tissues, which is crucial for patient safety and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing Online Adaptation Timing in the Treatment of Locally Advanced Cervical Cancer. Yen, A., Zhong, X., Lin, MH., et al.[2023]

Adaptive radiotherapy (ART) has shown promising results in improving treatment outcomes for various cancers, including prostate, bladder, gynecological, and ano-rectal cancers, by allowing for personalized adjustments based on tumor motion and response, with 43 clinical and 51 in silico studies reviewed.

Despite the demonstrated benefits of ART, such as better sparing of surrounding organs and improved dosimetric outcomes, its clinical implementation remains limited due to challenges in accurately re-contouring targets and selecting appropriate patients for ART workflows.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive radiotherapy strategies for pelvic tumors - a systematic review of clinical implementations. Thörnqvist, S., Hysing, LB., Tuomikoski, L., et al.[2018]

A working group of 11 experienced radiation oncologists identified essential components for safe online adaptive radiation therapy (ART), including recontouring instructions, replanning rules, and motion management guidelines.

Clear communication and structured guidelines are crucial when physicians cover ART treatments to ensure that the original treatment intent is preserved, especially during transitions of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive Radiation Therapy Physician Guidelines: Recommendations From an Expert Users' Panel. Kim, H., Lee, P., Tree, AC., et al.[2022]

An adaptive plan selection strategy for radiotherapy in rectal cancer patients improved target volume coverage in some cases, specifically enhancing mesorectum coverage for one patient.

The adaptive approach also resulted in significant reductions in bladder and bowel radiation exposure, with a 6.9% decrease in bladder coverage and an 18.4 cm³ reduction in bowel cavity exposure, indicating potential benefits for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential dosimetric benefit of an adaptive plan selection strategy for short-course radiotherapy in rectal cancer patients. Lutkenhaus, LJ., de Jong, R., Geijsen, ED., et al.[2018]

Adaptive radiotherapy (ART) is beneficial for tumors with significant anatomical variations, such as those in the head and neck, lung, bladder, and cervix, as it allows for multiple treatment plans to be adjusted based on changes during irradiation.

While ART shows clear dosimetric advantages, its clinical benefits have not yet been formally proven, and it requires further evaluation in prospective trials before being implemented in routine practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adaptive radiotherapy: Strategies and benefits depending on tumor localization]. Briens, A., Castelli, J., Barateau, A., et al.[2019]

Online adaptive radiotherapy (oART) significantly reduced radiation exposure to organs at risk (OARs) in anal cancer patients, with median reductions of 11.4% for the bowel and 16.1% for the bladder compared to standard non-adaptive radiotherapy.

The study found that while oART is feasible for clinical use, it is time-consuming, with an average procedure time of 23 minutes, and requires a combination of rigid and deformed target propagation methods to ensure effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Online adaptive radiotherapy of anal cancer: Normal tissue sparing, target propagation methods, and first clinical experience. Åström, LM., Behrens, CP., Storm, KS., et al.[2022]

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