Adaptive Radiation Therapy for Cervical Cancer

(ARTIA-Cervix Trial)

Recruiting at 5 trial locations

Overseen By Heike Hausen, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Varian, a Siemens Healthineers Company

Must be taking: Cisplatin

Disqualifiers: Prior radiation, Autoimmune disease, Pregnancy, 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: Unknown

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method of using radiation therapy to treat advanced cervical cancer. The goal is to determine if this adaptive approach can reduce stomach and gut problems often associated with traditional radiation treatment. Participants will receive daily radiation therapy using the Varian Ethos Adaptive Radiation Therapy system. Suitable candidates have advanced cervical cancer, have not undergone a hysterectomy, and plan to receive radiation and chemotherapy together. As an unphased trial, this study allows patients to contribute to innovative research that could enhance future treatment options.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial involves chemotherapy and radiation, it's important to discuss your current medications with the trial team to ensure there are no interactions.

What prior data suggests that adaptive radiation therapy is safe for cervical cancer patients?

Research has shown that adaptive radiation therapy (ART) is generally safe. Studies on daily ART report low levels of immediate side effects, such as nausea or fatigue, compared to other treatments.

ART is designed to be more precise, targeting tumors while protecting healthy tissues. This precision can lead to fewer unwanted side effects. Research also indicates that ART enhances treatment safety by delivering lower radiation doses to nearby organs.

Overall, evidence suggests that ART, particularly with the Varian Ethos system, is well-tolerated and safe for patients. However, as with any treatment, individual experiences may vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for cervical cancer rely on standard radiation therapy, which is planned at the start and remains unchanged throughout the treatment course. However, the Varian Ethos Adaptive Radiation Therapy is unique because it adapts the radiation dose each day based on daily changes in the tumor and surrounding organs. This approach allows for more precise targeting of the cancer, potentially increasing effectiveness and reducing side effects. Researchers are excited about this treatment because it offers a personalized approach, tailoring therapy to the patient's daily anatomical changes, which could lead to better outcomes and fewer complications.

What evidence suggests that Varian Ethos Adaptive Radiation Therapy is effective for cervical cancer?

Research has shown that adaptive radiation therapy, such as the Varian Ethos system, might reduce side effects in cervical cancer treatment. One study found that this method decreased short-term stomach and intestinal issues, common with standard treatments. It also demonstrated better control of radiation doses to targeted areas compared to traditional methods. This trial will evaluate the Varian Ethos system's ability to deliver radiation more precisely, potentially protecting healthy tissues and making treatment more comfortable for patients. ^{1 3 5 6 7}

Who Is on the Research Team?

Jyoti Mayadev, MD

Principal Investigator

University of California, San Diego

Xenia Ray, PhD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed advanced cervical cancer (stages IB2-IVA) who haven't had a hysterectomy or previous cancer treatments. Participants must be planning concurrent chemo and radiation, have good performance status, no severe allergies to cisplatin, and normal organ/marrow function. They should not be pregnant/breastfeeding and must agree to use birth control.

Inclusion Criteria

I am not allergic to cisplatin or similar drugs.

total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)

AST(SGOT)/ALT(SGPT) ≤ 3 × ULN

Exclusion Criteria

I have another type of cancer diagnosed at the same time, but it's not early skin cancer or DCIS of the breast.

I had surgery to remove lymph nodes in my pelvis or near my aorta before starting chemoradiation.

I have or had a fistula connecting my bladder, bowel, or colon to my vagina.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive daily adaptive external beam radiation therapy for cervical cancer

5 weeks

Daily visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Varian Ethos Adaptive Radiation Therapy

Trial Overview The study tests Varian Ethos Adaptive Radiation Therapy in patients with locally advanced cervical cancer. It aims to show that this individualized treatment can reduce acute gastrointestinal side effects compared to traditional non-adaptive IMRT by week 5 of external beam radiotherapy.

How Is the Trial Designed?

Group I: Daily Adaptive External Beam Radiation Therapy Experimental Treatment 1 Intervention

Daily adaptive radiation therapy delivered with Varian Ethos treatment system.

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

Approved in United States as Varian Ethos Adaptive Radiation Therapy for:

• Locally advanced cervical cancer

Approved in European Union as Varian Ethos Adaptive Radiation Therapy for:

• Locally advanced cervical cancer

Who Is Running the Clinical Trial?

Varian, a Siemens Healthineers Company

Lead Sponsor

Trials

35

Recruited

7,200+

Published Research Related to This Trial

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]

The Ethos™ adaptive radiation therapy platform improved the dose to the clinical target volume (CTV) for most prostate cancer patients without requiring time-consuming manual edits, showing a 2.9% increase in CTV D98% for 24 out of 25 patients.

While the system generally performed well, one patient experienced significant under-contouring of the CTV, highlighting the need for careful review of auto-segmentation results, as not all patients may be suitable for this adaptive approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospects for daily online adaptive radiotherapy via ethos for prostate cancer patients without nodal involvement using unedited CBCT auto-segmentation. Moazzezi, M., Rose, B., Kisling, K., et al.[2022]

In a study involving 10 cervical cancer patients, daily plan selection adaptive radiation therapy (RT) significantly improved target coverage, achieving over 98% coverage compared to 17% inadequacy with non-adaptive RT.

Adaptive RT also reduced radiation exposure to the rectum and bowel, while it did lead to increased doses to the bladder, highlighting the need for careful monitoring of organ at risk during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric advantages of a clinical daily adaptive plan selection strategy compared with a non-adaptive strategy in cervical cancer radiation therapy. van de Schoot, AJAJ., de Boer, P., Visser, J., et al.[2022]

The automated treatment planning system (aTPS) for online adaptive radiotherapy (oART) produced plans for 60 patients with pelvic cancers that were comparable in quality to manually generated plans, demonstrating effective target coverage and organ at risk (OAR) sparing.

The median time to generate treatment plans using aTPS was relatively short, ranging from 35 to 55 minutes, making it a practical option for improving the efficiency of radiotherapy planning without compromising plan quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of an automated template-based treatment planning system for radiotherapy of anal, rectal and prostate cancer. Calmels, L., Sibolt, P., Åström, LM., et al.[2022]

Adaptive radiotherapy (ART) using the PTVART Library approach provided the best dosimetric results for cervix cancer patients, offering improved sparing of organs at risk (OAR) while maintaining target coverage.

Using static margins like PTV15mm increased doses to OARs, while smaller margins compromised target coverage; however, ITV margins based on early treatment evaluations also showed significant benefits over static concepts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of organ shape variations on margin concepts for cervix cancer ART. Seppenwoolde, Y., Stock, M., Buschmann, M., et al.[2018]

The study evaluated six Ethos therapy systems for adaptive radiation therapy, finding excellent agreement between machine measurements and vendor reference data, indicating reliable performance across systems.

Minimal variations were observed in key dosimetric and mechanical characteristics, such as dosimetric leaf gap and isocenter accuracy, suggesting that these machines can be interchangeably used for patient treatment with confidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of Ethos therapy systems for adaptive radiation therapy: A multi-machine comparison. van de Schoot, AJ., Hoffmans, D., van Ingen, KM., et al.[2023]

The plan-of-the-day (PotD) adaptive approach to radiation therapy for locally advanced cervical cancer has been shown to improve target coverage and reduce radiation exposure to normal tissues, potentially decreasing toxicity.

Despite its benefits, the clinical implementation of PotD has faced challenges, and this paper provides a framework to help healthcare teams effectively adopt this approach in their practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carpe Diem: Making the Most of Plan-of-the-Day for Cervical Cancer Radiation Therapy. Wang, L., Alexander, S., Mason, S., et al.[2023]

The commissioning of the Ethos® therapy system at the Montpellier Cancer Institute showed that the beam delivery and treatment planning system (TPS) were validated with high accuracy, achieving a gamma index pass rate above 98% for all measurements, indicating reliable dose calculations.

The Ethos Acuros XB algorithm was validated for various treatment configurations, including fixed fields and advanced techniques like IMRT and VMAT, with gamma pass rates exceeding 99%, demonstrating its efficacy and safety for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive commissioning and quality assurance validation of Ethos™ therapy. Morel, A., Prunaretty, J., Trauchessec, D., et al.[2023]

Adaptive Radiotherapy (ART) can significantly reduce bowel radiation exposure in cervical cancer patients, particularly for those with higher initial bowel doses, as shown by a strong correlation (R2=0.77 for 3 mm margins and R2=0.8 for 5 mm margins).

The study developed predictive models to identify which patients would benefit most from ART, allowing for better allocation of resources in clinical settings, with a validation R2 of 0.66 for predicting adaptive benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Forecasting patient-specific dosimetric benefit from daily online adaptive radiotherapy for cervical cancer. Ghimire, R., Moore, KL., Branco, D., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05197881

Study Details | NCT05197881 | Daily Adaptive Radiation ... This is a single-arm, prospective, multi-center clinical trial designed to demonstrate that adaptive radiotherapy for locally advanced cervical cancer will ...

2. redjournal.org redjournal.org/article/S0360-3016(25)00309-8/fulltext

Acute Toxicity and Dosimetric Outcomes To our knowledge, this is the first clinical study reporting the acute toxicity and dosimetric outcomes of daily oART for cervical cancer. The iCBCT-guided oART ...

3. varian.com varian.com/resources-support/blogs/ethos-adaptive-radiotherapy-program-established-peking-union

Ethos Adaptive Radiotherapy Program Established at ... Research team launches clinical trial looking at adaptive radiotherapy for the postoperative treatment of cervical and endometrial cancer.

4. advancesradonc.org advancesradonc.org/article/S2452-1094(24)00113-1/fulltext

Using Scorecards to Tune Ethos Directive Templates In this study, we demonstrated that a dosimetric scorecard is an effective tool for tuning an Ethos CDT to improve plan quality for cervical ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11602513/

First implementation and results of online adaptive ... This trial revealed the dosimetric benefits of daily ART for cervical cancer over IGRT. · In patients with rectal cancer and cervical cancer, ...

6. varian.com varian.com/resources-support/blogs/investing-clinical-research-improve-patient-outcomes-ethostm

Investing in Clinical Research to Improve Patient Outcomes Adaptive radiotherapy has great potential to provide cancer patients with more precise and personalized treatment than was possible before.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11140188/

Daily Online Adaptive Radiation Therapy of Postoperative ... Daily oART was associated with favorable dosimetry improvement and low acute toxicity, supporting its safety and efficacy for postoperative treatment of ...