Adaptive Radiation Therapy for Stage III Lung Cancer

(ARTIA-Lung Trial)

Overseen By Steve Kohlmyer, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Varian, a Siemens Healthineers Company

Disqualifiers: Prior thorax RT, Severe COPD, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to radiation therapy for individuals with stage III non-small cell lung cancer (NSCLC). It compares a tailored radiation treatment, known as Adaptive Radiotherapy, which adjusts daily to tumor changes, with the standard radiation method. Both methods are paired with chemotherapy. Researchers aim for this new method to cause fewer short-term side effects, such as breathing or swallowing issues. Suitable candidates have NSCLC that cannot be operated on and show no signs of cancer spreading to other parts of the body. As an unphased trial, this study allows patients to contribute to innovative research that could enhance future cancer treatments.

Do I need to stop my current medications for this 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 coordinators or your doctor.

What prior data suggests that adaptive radiotherapy is safe for stage III lung cancer?

Research has shown that adaptive radiotherapy is generally safe for treating lung cancer. Studies have found no major differences in severe side effects, such as those affecting the lungs, esophagus, or heart, when comparing adaptive radiotherapy to other treatments. This indicates that patients can tolerate the treatment well.

Patients receiving adaptive radiotherapy do not experience higher rates of severe side effects, confirming its safety. The treatment involves adjusting the radiation plan daily to account for changes in the tumor and surrounding area. This approach targets the cancer more effectively and reduces harm to healthy tissue.

Overall, adaptive radiotherapy appears to be a promising and safe choice for those considering treatment for stage III non-small cell lung cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the adaptive radiation therapy technique for stage III lung cancer because it offers a personalized approach to radiotherapy. Unlike standard treatments, which use a fixed radiation plan, adaptive radiotherapy adjusts the radiation dosimetry daily to account for changes in the tumor and surrounding anatomy. This real-time adaptation is achieved using advanced imaging technology, potentially improving targeting accuracy and reducing damage to healthy tissue. By tailoring treatment to the patient’s daily condition, this method could enhance treatment effectiveness and reduce side effects, offering a promising new direction in cancer care.

What evidence suggests that this trial's treatments could be effective for stage III lung cancer?

Research has shown that adaptive radiotherapy, which participants in the Adaptive Arm of this trial will receive, can effectively treat non-small cell lung cancer (NSCLC). Studies have found that it reduces the risk of radiation pneumonitis, a lung issue caused by radiation treatment. Adaptive radiotherapy adjusts the radiation dose daily to better target the tumor. This approach can control the cancer in the treated area and reduce the radiation exposure to the lungs, while still effectively treating the cancer. These benefits may improve quality of life by reducing treatment side effects. ^{1 3 4 6 7}

Who Is on the Research Team?

Andrew McDonald, MD

Principal Investigator

University of Alabama at Birmingham

Dennis Stanley, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for adults over 18 with stage IIIA-IIIB non-small cell lung cancer (NSCLC) who are not candidates for surgery. Participants must have no distant metastases, normal organ and marrow function, and an ECOG performance status of 0-2. They should not have had previous thoracic radiation or other cancers within the last three years.

Inclusion Criteria

My cancer can be measured by tests.

My organs and bone marrow are functioning normally.

I had a PET-CT scan within the last 2 months.

Exclusion Criteria

If there are big issues with the pictures that make it hard to see the chest and tumors clearly, you might not be able to join the study. For example, if you have a medical device near the area being looked at, it might cause problems with the pictures.

I do not have severe COPD or other lung problems that would stop me from receiving the study treatment.

My tests show cancer cells in the fluid around my lungs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Chemotherapy

Participants receive daily online adaptive radiotherapy or standard image-guided radiation therapy with concurrent chemotherapy

8 weeks

Daily visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of acute toxicity and overall response rate

12 months

Regular follow-up visits

Long-term Follow-up

Participants are monitored for long-term outcomes such as local progression and radiation pneumonitis

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Adaptive Radiotherapy
• Chemotherapy

Trial Overview The study compares daily online adaptive radiotherapy combined with chemotherapy against standard non-adaptive radiotherapy with chemotherapy in treating stage III NSCLC. The goal is to see if the adaptive method reduces acute respiratory and esophageal toxicity one month post-treatment.

How Is the Trial Designed?

Group I: Adaptive Arm Experimental Treatment 3 Interventions

Subjects in this arm will receive their external beam radiotherapy on the Ethos Radiotherapy System version 2.0 with HyperSight cone beam computed tomography imaging, with daily online adaptation of their radiation dosimetry plan to account for day-to-day changes in the tumor and surrounding anatomical structures. All subjects will received standard concurrent chemotherapy and may receive adjuvant immunotherapy, if indicated.

Group II: Non-Adaptive Arm Active Control 3 Interventions

Subjects in this arm will receive their radiotherapy using standard image-guided radiation therapy (IMRT) techniques. All subjects will receive standard concurrent chemotherapy and may receive adjuvant immunotherapy, if indicated.

Adaptive Radiotherapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Trodelvy for:

• Metastatic triple-negative breast cancer (mTNBC)
• Metastatic hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer
• Metastatic urothelial cancer (approval being withdrawn)

Approved in European Union as Trodelvy for:

• Metastatic triple-negative breast cancer (mTNBC)
• Metastatic urothelial cancer

Approved in Canada as Trodelvy for:

• Metastatic triple-negative breast cancer (mTNBC)
• Metastatic urothelial 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

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and delivers a topoisomerase I inhibitor, showing promise in treating metastatic triple-negative breast cancer (mTNBC) after at least two prior therapies.

In April 2020, it received accelerated approval in the USA for mTNBC, and it is currently undergoing further clinical trials for various cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. Syed, YY.[2021]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and has shown a 33.3% overall response rate in patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies, based on a phase I/II study with 108 participants.

The treatment has a median duration of response of 7.7 months, and while it is generally well-tolerated, common side effects include nausea, neutropenia, and fatigue, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. Seligson, JM., Patron, AM., Berger, MJ., et al.[2021]

In a study of 50 patients with metastatic small cell lung cancer (mSCLC) who had been heavily pretreated, sacituzumab govitecan demonstrated a 14% objective response rate, with 60% of patients showing tumor shrinkage, indicating its potential efficacy as a treatment option.

The treatment was found to be generally safe, with manageable side effects; however, significant adverse events included neutropenia (34%) and fatigue (13%). This suggests that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. Gray, JE., Heist, RS., Starodub, AN., et al.[2022]

Adaptive radiotherapy (ART) can significantly reduce the gross tumor volume (GTV) in patients with stage III non-small cell lung cancer (NSCLC), with an average reduction of 42.1%, particularly benefiting those undergoing concurrent chemoradiotherapy (cCRT).

The most effective time to implement ART is around the 15th treatment fraction, as this timing provides the best dosimetric advantages, especially for patients with larger tumors, while also allowing for better management of lung dose constraints.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive radiotherapy for locally advanced non-small cell lung cancer, can we predict when and for whom? Berkovic, P., Paelinck, L., Lievens, Y., et al.[2018]

The TREASURE trial is a phase II clinical study involving 104 patients with extensive disease small cell lung cancer (SCLC) to evaluate the effectiveness of adding thoracic radiotherapy (TRT) to atezolizumab maintenance therapy after initial chemo-immunotherapy, with overall survival as the primary endpoint.

This trial aims to enhance treatment outcomes by exploring the synergistic effects of combining immunotherapy with radiotherapy, while also assessing safety and collecting biomarker samples for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol of the TREASURE study: Thoracic RadiothErapy with Atezolizumab in Small cell lUng canceR Extensive disease - a randomized, open-label, multicenter phase II trial. Bozorgmehr, F., Christopoulos, P., Chung, I., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8666420/

Adaptive Radiation Therapy in the Treatment of Lung Cancer While it has been shown that daily CBCT can reduce the risk of pneumonitis in unresectable NSCLC (38), ART may offer an even greater benefit. In ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05488626

Study Details | NCT05488626 | Daily Adaptive Radiation ... This is a prospective multi-center randomized clinical trial designed to demonstrate that daily online adaptive radiotherapy with concomitant chemotherapy for ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301624003717

Adapt or Perish: Adaptive RT for NSCLC However, median progression-free survival (PFS) remains 16.9 months after chemoradiation of 60 to 66 Gy for those receiving adjuvant durvalumab.1 Furthermore, ...

4. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-023-02222-7

Dosimetric benefits of adaptive radiation therapy for patients ... We demonstrated that even without reducing safety margins, ART can reduce lung-doses, while still reaching adequate target coverage or escalate target doses.

5. thegreenjournal.com thegreenjournal.com/article/S0167-8140(22)00065-2/fulltext

Survival benefits for non-small cell lung cancer patients ... Tumor match and adaptive radiotherapy significantly decreased radiation pneumonitis, while maintaining loco-regional control. Further, we ...

6. nrgoncology.org nrgoncology.org/Home/News/Post/nrg-oncology-trial-results-show-safety-of-adaptive-radiotherapy-in-non-small-cell-lung-cancer-patients-open-paths-to-future-prospective-studies

NRG Oncology Trial Results Show Safety of Adaptive ... There were no significant differences in grade 3 or worse toxicity of lung, esophagus, and heart or overall survival, progression-free survival, ...

7. advancesradonc.org advancesradonc.org/article/S2452-1094(25)00193-9/fulltext

Safety and Efficacy of Stereotactic MR-Guided Adaptive ... This retrospective study analyzed outcomes of SMART-based SABR for ultracentral metastatic lesions in patients with histologically confirmed non-small cell lung ...