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

244 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new way of giving radiation therapy that adjusts regularly based on the patient's condition, combined with chemotherapy. It aims to help people with stage III non-small cell lung cancer. The goal is to reduce side effects like breathing and swallowing problems by targeting the cancer more precisely.

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 data supports the effectiveness of the treatment Adaptive Radiotherapy for Stage III Lung Cancer?

Research shows that combining chemotherapy with radiation therapy can improve survival in patients with Stage III lung cancer. Adaptive radiotherapy, which adjusts treatment based on changes in tumor size, is being explored to enhance this approach by reducing harm to healthy tissue. ^{1 2 3 4 5}

Is adaptive radiation therapy for stage III lung cancer safe?

Adaptive radiation therapy, which adjusts treatment based on changes in tumor size, is being studied for its safety and effectiveness. Advances in targeting and planning have made it more feasible and reduced the risk of harming normal tissues. ^{2 4 6 7 8}

How is the treatment for stage III lung cancer using adaptive radiotherapy and sacituzumab govitecan different from other treatments?

This treatment is unique because it combines adaptive radiotherapy, which adjusts the radiation plan based on changes in tumor size, with sacituzumab govitecan, a drug that targets a protein called Trop-2 on cancer cells and delivers a chemotherapy agent directly to them, potentially reducing side effects and improving effectiveness. ^{4 9 10 11 12}

Research Team

Andrew McDonald, MD

Principal Investigator

University of Alabama at Birmingham

Dennis Stanley, PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Chemoradioimmunotherapy of inoperable stage III non-small cell lung cancer: immunological rationale and current clinical trials establishing a novel multimodal strategy. [2021]

2. England 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. [2022]

3. Poland pubmed.ncbi.nlm.nih.gov

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Novel approaches of chemoradiotherapy in unresectable stage IIIA and stage IIIB non-small cell lung cancer. [2021]

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Impact of epidermal growth factor receptor sensitizing mutations on outcomes of patients with non-small cell lung cancer treated with definitive thoracic radiation therapy: a systematic review and meta-analysis. [2023]

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Role of consolidative thoracic radiation in extensive-stage small-cell lung cancer with first-line chemoimmunotherapy: a retrospective study from a single cancer center. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

Treatment-related pulmonary adverse events induced by chemoradiation and Durvalumab affect survival in locally advanced non-small cell lung cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial. [2023]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Adaptive radiotherapy for locally advanced non-small cell lung cancer, can we predict when and for whom? [2018]

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

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021]

12. United States 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. [2022]