Adaptive Radiotherapy for Small Cell Lung Cancer

(DARTS Trial)

Overseen By Yee Don, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AHS Cancer Control Alberta

Must not be taking: Dexamethasone

Disqualifiers: Brain metastasis, Previous chemotherapy, 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

Compensation: Varies

Number of Visits: Unknown

31 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores adaptive radiotherapy for treating small cell lung cancer (SCLC). The aim is to evaluate how effectively this targeted radiation approach controls cancer and minimizes side effects when combined with chemotherapy, which uses drugs to destroy cancer cells. The trial adjusts the radiation dose in phases to best fit each patient’s condition. Suitable participants have newly diagnosed, untreated small cell lung cancer that can be targeted with radiation. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 radiotherapy, it's best to discuss your current medications with the study team to ensure there are no interactions.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Past research on adaptive radiotherapy for lung cancer has shown promise in controlling tumors, though it can sometimes cause serious side effects. One study found the treatment effective, but some patients experienced severe side effects, known as grade 3 or higher toxicities, which significantly impacted their health.

Another study observed that as the tumor shrinks during treatment, the radiation dose to nearby organs can decrease, potentially reducing side effects. This suggests that adaptive radiotherapy can adjust during treatment to become safer.

Overall, while adaptive radiotherapy is promising, potential side effects should be considered when deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Adaptive radiotherapy for small cell lung cancer is unique because it tailors the radiation dose throughout the treatment process, optimizing effectiveness while protecting healthy tissues. Unlike traditional radiotherapy, this approach uses multiple phases and scheduled replans to adjust doses based on how the tumor and surrounding organs respond. Researchers are excited because this method allows higher doses to be delivered safely, potentially improving outcomes without increasing side effects. By using advanced planning techniques like IMRT, it could lead to more precise and personalized cancer treatment.

What evidence suggests that dose-escalated adaptive radiotherapy is effective for small cell lung cancer?

Research has shown that adaptive radiotherapy, which adjusts radiation doses during treatment, can help control lung cancer by more accurately targeting cancer cells. In this trial, participants will receive dose-escalated adaptive chemoradiotherapy, combining adaptive radiotherapy with standard chemotherapy. Some studies have reported significant tumor shrinkage and reduced radiation exposure to healthy organs. This approach aims to deliver higher doses directly to the cancer while minimizing harm to nearby tissues. The goal is to enhance the effectiveness of radiation treatment and reduce side effects. Overall, adaptive radiotherapy shows promise in better managing lung cancer growth. ^{2 3 4 6 7}

Who Is on the Research Team?

Yee Don, MD

Principal Investigator

Cross Cancer Institute, Alberta Health Services

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed, untreated Small Cell Lung Cancer (SCLC) who can undergo platinum chemotherapy and thoracic radiotherapy. They must have completed standard cancer staging tests, be able to consent, follow the study plan, and have a performance status of ECOG 0-2. People with severe infections, less than 3 months life expectancy, previous cancers (except certain skin cancers), prior chemo or thoracic surgery are excluded.

Inclusion Criteria

My lung disease can be treated with radiation.

I am eligible for chest radiation therapy, including treatment to the lymph nodes above my collarbone.

I have been newly diagnosed with small cell lung cancer and have not received any treatment.

Exclusion Criteria

My brain cancer has not been stable even with dexamethasone treatment.

I have undergone chemotherapy before.

My lung cancer has spread to areas near my chest but not beyond my collarbone lymph nodes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiotherapy Phase 1

Participants receive 14 Gy in 7 fractions of adaptive dose-escalated radiotherapy

1-2 weeks

Radiotherapy Phase 2

Participants receive 10 Gy in 5 fractions starting the day after the final (7th) fraction of Phase 1

1 week

Radiotherapy Phase 3

Participants receive up to 70 Gy in 35 fractions or the maximum safe dose

3-4 weeks

Follow-up

Participants are monitored for local failure rate, progression-free survival, overall survival, and radiation toxicity

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Chemotherapy
• Dose-escalated Adaptive Radiotherapy

Trial Overview The study is testing the effects of dose-escalated adaptive radiotherapy in combination with chemotherapy on lung cancer control and side effects. Adaptive radiotherapy adjusts doses based on changes in tumor size or position during treatment to better target the disease.

How Is the Trial Designed?

Group I: Dose-escalated adaptive chemoradiotherapy Experimental Treatment 2 Interventions

Concurrent with standard of care platinum doublet based chemotherapy (cisplatin + etoposide), radiation treatment plan will be delivered in three sequential phases with two scheduled replans during the treatment along with scaled dose limits for organs-at-risk: Phase 1 dose prescription = 14 Gy in 7 fractions; Phase 2 dose prescription = 10 Gy in 5 fractions starting the day after the final (7th) fraction is delivered; Phase 3 dose prescription = either a) 70 Gy in 35 fractions, or if this cannot be safely reached without exceeding the dose limit of an organ-at-risk, b) the maximum safe prescribe-able dose tolerance specified in the protocol. Either 3D conformal radiotherapy or IMRT planning and delivery techniques will be employed, including contouring relevant thoracic organs-at-risk. All CT simulation scans will be without contrast.

Chemotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in United States as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Canada as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Japan as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in China as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Switzerland as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Who Is Running the Clinical Trial?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Published Research Related to This Trial

There is currently no standard therapy for limited small cell lung cancer, with chemotherapy regimens typically being cyclophosphamide-based but varying widely in their specifics.

Recent trials indicate that radiotherapy is effective in improving local control of small cell lung cancer, highlighting the need for further research to determine the best combinations and timing of chemotherapy and radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited small cell lung cancer--the role of radiotherapy. Turrisi, AT.[2005]

Using a fixed margin treatment approach in radiotherapy can lead to significant under-dosage of the clinical target volume (CTV), with more than 5Gy less delivered than intended.

Both on-line and off-line adaptive radiotherapy strategies can effectively restore CTV coverage while maintaining acceptable doses to organs at risk (OAR), with the off-line strategy being more practical and sufficient for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dosimetric evaluation of IGART strategies for cervix cancer treatment. O'Reilly, FH., Shaw, W.[2019]

The combination of chemotherapy and external beam thoracic radiotherapy significantly improves local control and overall survival in patients with limited stage small cell lung carcinoma, which affects 20-30% of patients at diagnosis.

While cisplatin with etoposide is the standard chemotherapy regimen, the optimal radiotherapy dose and schedule for treating limited stage small cell lung cancer remains unclear, with new approaches like hyperfractionated and hypofractionated radiotherapy being explored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined modality treatment of limited stage small cell carcinoma of the lung. Yee, D., Danielson, B., Roa, W.[2019]

In a study of 55 patients with limited small cell lung cancer, the combination of chemotherapy and hyperfractionated accelerated radiotherapy resulted in a high overall response rate of 87.3% and median survival time of 18.7 months, with 1-, 3-, and 5-year survival rates of 79.1%, 40.3%, and 16.1%, respectively.

The treatment was associated with mild to moderate toxicities, including hematologic issues in 41.8% of patients and radiation-induced pneumonitis and esophagitis in a significant number, but no severe non-hematologic toxicities were reported, indicating a tolerable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of chemotherapy combined hyperfractionated accelerated radiotherapy on limited small cell lung cancer]. Hu, X., Bao, Y., Chen, YY., et al.[2019]

Real-time image-guided adaptive radiation therapy (IGART) using standard linear accelerators was successfully implemented in a study involving eight prostate cancer patients, achieving a high success rate of 95% for treatment fractions.

The use of Kilovoltage Intrafraction Monitoring (KIM) and multileaf collimator (MLC) tracking improved the accuracy of radiation delivery, ensuring that 100% of the target volume received the prescribed dose during the largest motion fraction, compared to only 95% without IGART.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The first clinical implementation of real-time image-guided adaptive radiotherapy using a standard linear accelerator. Keall, PJ., Nguyen, DT., O'Brien, R., et al.[2019]

The modified combined therapy of cisplatin/etoposide and hyperfractionated accelerated radiation therapy (HART) was well-tolerated by limited-stage small-cell lung cancer patients, with 54 out of 57 completing the treatment, indicating its feasibility in a developing country context.

The median survival time was 24 months, with 1-year and 2-year survival rates of 81% and 49%, respectively, suggesting that this treatment approach offers better tumor control and survival compared to conventional radiation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin/etoposide chemotherapy combined with twice daily thoracic radiotherapy for limited small-cell lung cancer: a clinical phase II trial. Chen, GY., Jiang, GL., Wang, LJ., et al.[2013]

In a study of 138 locally advanced cervical cancer patients undergoing image-guided adaptive radiotherapy (IGART), quality of life (QoL) significantly declined during treatment, peaking at the end of external beam radiotherapy (EBRT) and returning to baseline levels three months post-treatment.

Specific symptoms, such as diarrhea and bowel cramps, worsened notably within the first three weeks of treatment, indicating that these side effects may require early management strategies to improve patient comfort during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamics of patient reported quality of life and symptoms in the acute phase of online adaptive external beam radiation therapy for locally advanced cervical cancer. Heijkoop, ST., Nout, RA., Quint, S., et al.[2017]

The study found that the ratio of Bcl-2 to Bim expression in small cell lung cancer (SCLC) cells can predict how sensitive these cells are to cisplatin treatment, with significant correlations observed in both mRNA and protein levels.

The BH3-mimetic drug ABT-263 was shown to enhance the effectiveness of cisplatin and radiation therapy in SCLC by promoting apoptosis, suggesting it could be a valuable addition to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ratio of Bcl-2/Bim as a predictor of cisplatin response provides a rational combination of ABT-263 with cisplatin or radiation in small cell lung cancer. Li, H., Wang, H., Deng, K., et al.[2019]

Chemoradiotherapy, particularly cisplatin-based chemotherapy combined with thoracic radiotherapy, results in a 5-year survival rate of about 15% for patients with unresectable locally advanced non-small cell lung cancer.

For limited-stage small cell lung cancer, the combination of cisplatin and etoposide with concurrent thoracic irradiation and prophylactic cranial irradiation leads to a higher 5-year survival rate of approximately 25%, highlighting the effectiveness of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy for lung cancer. Ohe, Y.[2019]

In a study of 23 breast cancer treatment plans, dose-guided adaptive radiation therapy (DGART) was shown to effectively correlate clinical expert evaluations with quantitative dose metrics, allowing for tailored treatment adjustments based on individual patient needs.

The use of dose-volume histogram (DVH) parameters demonstrated high sensitivity (0.89) and perfect specificity (1.0) in identifying patients who required treatment adaptations, indicating that DGART can enhance the precision of radiation therapy delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-dimensional dose evaluation in breast cancer patients to define decision criteria for adaptive radiotherapy. Zegers, CML., Baeza, JA., van Elmpt, W., et al.[2018]

In a study of 24 patients with limited-stage small cell lung cancer, adaptive radiation therapy (ART) allowed for significant reductions in tumor size and critical organ doses, improving treatment safety and efficacy.

One-third of patients who were previously ineligible for full-dose radiation due to critical organ constraints were able to receive the complete treatment thanks to ART, highlighting its potential benefits in managing LS-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive radiation therapy (art) for patients with limited-stage small cell lung cancer (LS-SCLC): A dosimetric evaluation. Sager, O., Dincoglan, F., Demiral, S., et al.[2023]

In a study of 39 patients with small cell lung cancer (SCLC), a combination of chemotherapy (COPE regimen) and radiotherapy resulted in an overall response rate of 82.8%, with 28.6% achieving complete response and 54.2% partial response.

The treatment was well tolerated, with granulocytopenia being the most common side effect, and the median survival was 52 weeks, indicating that this approach is effective for both limited and extensive disease stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination chemotherapy with cyclophosphamide, vincristine, cisplatin and etoposide (COPE) combined with radiotherapy for small cell lung cancer. Nam, YJ., Choi, CW., Shin, SW., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11730452/

Locally advanced non-small cell lung cancer A phase 2 single-arm study demonstrated that adaptive radiotherapy-escalated radiation dose to the mid-treatment FDG-PET-avid region (up to ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04952480

Dose-escalated Adaptive Radiotherapy of Thoracic ... The purpose of this study is to find out what effects of using adaptive radiotherapy to deliver chest radiation has on the ability to control lung cancer ...

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

Adapt or Perish: Adaptive RT for NSCLC The primary goal of adaptive radiation therapy (ART) for lung cancer is reducing normal tissue irradiated, which requires careful consideration and study.

4. thegreenjournal.com thegreenjournal.com/article/S0167-8140(21)06082-5/fulltext

Is a routine adaptation beneficial? A median of −38.2% tumor shrinkage was found after 20 fractions of 42.8 to 44 Gy irradiation. The dose to OARs significantly decreased.

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

Adaptive Radiation Therapy in the Treatment of Lung Cancer This article presents an overview of the current state of the field in ART for lung cancer, specifically, probing topics of: patient selection for the greatest ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3665644/

Dose Escalation for Locally Advanced Lung Cancer using ... Adaptive radiotherapy for locally advanced non-small-cell lung cancer does not underdose the microscopic disease and has the potential to increase tumor control ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6411023/

A Current Review of Dose-escalated Radiotherapy in Locally ... Dose escalation by simply increasing fraction numbers results in lengthened overall treatment, which has proven to have a negative impact on ...