Radiation + Chemotherapy for Advanced Lung Cancer

Overseen By Jenna Gregory, RN, BSN, OCN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Atrium Health

Disqualifiers: Prior systemic therapy, Prior chest radiation, Active on other study, Prior invasive malignancy, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of radiation and chemotherapy treatments to evaluate their effectiveness for individuals with locally advanced lung cancer. The focus is on improving the one-year progression-free survival rate, meaning the cancer does not worsen during this period. Participants will receive Stereotactic Body Radiation Therapy (SBRT) along with the chemotherapy drugs Carboplatin and Paclitaxel. This study may suit those diagnosed with stage II or III non-small cell lung cancer (NSCLC) who have not received prior treatments for their lung cancer. As a Phase 2 trial, the research aims to measure the treatment's effectiveness in an initial, smaller group of participants.

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 study team or your doctor to get a clear answer based on your specific situation.

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

Previous studies have well-documented the safety of Stereotactic Body Radiation Therapy (SBRT). However, one possible treatment-related death occurred due to lung inflammation and infection. Larger treatment areas correlated with more severe side effects.

Research on the chemotherapy drug carboplatin has shown it is generally safe for treating lung cancer, with common side effects including low blood cell counts and fatigue. Similarly, paclitaxel, another chemotherapy drug, is usually well-tolerated but can cause hair loss and nerve damage in some patients.

Overall, these treatments have been used successfully in lung cancer cases, but potential side effects require consideration. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about combining SBRT (Stereotactic Body Radiation Therapy) with chemotherapy for advanced lung cancer because it offers precision and power. Unlike standard treatments that involve broader radiation fields, SBRT delivers high doses of radiation directly to the tumor with pinpoint accuracy, minimizing damage to surrounding healthy tissue. This precision, coupled with the potent effects of chemotherapy drugs like Carboplatin and Paclitaxel, could enhance the overall effectiveness of treatment. Additionally, the trial explores the potential of adding consolidation chemotherapy or adjuvant immunotherapy, which could further boost the immune system's ability to fight cancer. This combination approach aims to improve outcomes for patients with advanced lung cancer where current treatment options are limited.

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

Research has shown that Stereotactic Body Radiation Therapy (SBRT), which participants in this trial will receive, effectively controls lung cancer locally and improves survival rates with few side effects. Studies suggest SBRT is a safe and effective treatment for non-small cell lung cancer (NSCLC), particularly in its early stages and possibly in more advanced stages.

Participants in this trial will also receive chemotherapy drugs such as Carboplatin and Paclitaxel, which have proven effective in treating advanced NSCLC. One study found that these drugs helped shrink tumors and slow cancer growth in 55% of patients. Together, these treatments could offer a strong option for managing advanced lung cancer. ^{4 5 6 7 8}

Who Is on the Research Team?

John H Heinzerling

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults over 18 with stage II or III non-small cell lung cancer (NSCLC) who haven't had systemic therapy for lung cancer or radiation that overlaps with the study area. They must have a certain level of lung function and agree to use contraception if they can have children. People with tumors too close to central airways, on other trials, or with recent invasive cancers are excluded.

Inclusion Criteria

My lung function is within the required range, and if I'm using oxygen, it's stable.

I can take care of myself but might not be able to do heavy physical work.

The effects of radiation on the developing human fetus are not well described. For this reason, women of child-bearing potential and non-sterilized men who are sexually active with a woman of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

Exclusion Criteria

I have been cancer-free for at least 3 years, except for certain low-risk or in situ cancers.

My lung tumor is close to the center and near important airways.

I've had chest radiation before that might affect new treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stereotactic Body Radiation Therapy (SBRT)

Participants receive Stereotactic Body Radiation Therapy to the primary tumor

2 months

Concurrent Mediastinal Chemoradiation

Participants receive concurrent mediastinal chemoradiation with or without consolidation chemotherapy

2 months

Adjuvant Immunotherapy

Participants may receive adjuvant immunotherapy following chemoradiation

4.5 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Durvalumab
• Etoposide
• IMRT
• Paclitaxel
• SBRT

Trial Overview The study tests high-dose radiation (SBRT) followed by chemotherapy and more radiation (IMRT) in people with advanced NSCLC. Some may also get consolidation chemo. Durvalumab might be added depending on what the doctor thinks is best. The goal is to see how patients do after one year.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 7 Interventions

SBRT + Concurrent Mediastinal Chemoradiation +/- Consolidation Chemotherapy/Adjuvant Immunotherapy

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Atrium Health

Lead Sponsor

Trials

122

Recruited

34,900+

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Atrium Health Levine Cancer Institute

Collaborator

Trials

30

Recruited

4,700+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

A combination treatment of paclitaxel, carboplatin, and oral etoposide was found to be highly effective and well tolerated in 117 patients with small-cell lung cancer, showing promising results in both extensive and limited stages of the disease.

The regimen can be safely administered alongside thoracic radiation therapy, with only a few patients experiencing esophagitis, indicating a favorable safety profile compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, carboplatin, and extended-schedule oral etoposide for small-cell lung cancer. Hainsworth, JD., Hopkins, LG., Thomas, M., et al.[2015]

Stereotactic body radiation therapy (SBRT) is recommended as a safe and effective treatment for patients with oligometastatic non-small cell lung cancer, particularly when there are 3 or fewer metastatic deposits, based on a review of literature from 2008 to 2020.

The American Radium Society Lung Cancer Panel advises that consolidative radiation therapy should follow first-line systemic therapy rather than being administered upfront, and emphasizes the importance of individualized treatment plans due to limited data on certain clinical scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

American Radium Society Appropriate Use Criteria for Radiation Therapy in Oligometastatic or Oligoprogressive Non-Small Cell Lung Cancer. Amini, A., Verma, V., Simone, CB., et al.[2022]

Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC) and has shown benefits over lower-dose radiotherapy regimens.

While SABR is generally safe and cost-effective, it can lead to increased toxicity in patients with tumors near the tracheobronchial tree or those with interstitial lung disease, highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiation therapy in lung cancer: an emerging standard. Mutsaers, A., Chen, H., Louie, AV.[2019]

The TROG 13.01/ALTG 13.001 clinical trial is investigating the safety and efficacy of single versus multi-fraction stereotactic ablative body radiotherapy (SABR) for lung tumors in 84 patients with up to three metastases, aiming to determine the best treatment approach for pulmonary oligometastases.

The study will compare a single high dose of 28Gy to a total of 48Gy delivered in four fractions, assessing not only safety but also quality of life, survival rates, and potential cost implications of each treatment method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised phase II trial of Stereotactic Ablative Fractionated radiotherapy versus Radiosurgery for Oligometastatic Neoplasia to the lung (TROG 13.01 SAFRON II). Siva, S., Kron, T., Bressel, M., et al.[2022]

In a study of 100 patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative body radiotherapy (SABR), the 1-, 2-, and 3-year local control rates were 100%, 93.55%, and 84.33%, respectively, indicating high efficacy in tumor control.

The treatment was associated with low toxicity, with only 2% of patients experiencing Grade-3 side effects, suggesting that SABR is a safe option for patients who are inoperable or refuse surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definitive Treatment of Early-Stage Non-Small Cell Lung Cancer with Stereotactic Ablative Body Radiotherapy in a Community Cancer Center Setting. Heal, C., Ding, W., Lamond, J., et al.[2020]

Combination therapy using paclitaxel with carboplatin and radiation shows promise as a safer and more effective treatment for non-small cell lung cancer compared to the standard regimen of etoposide and cisplatin.

The use of paclitaxel, a novel taxane drug, in conjunction with radiation therapy may enhance local control of the cancer and improve overall response rates, suggesting a potential advancement in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent paclitaxel, carboplatin, and radiation therapy for locally advanced non-small cell lung cancer. Choy, H., Akerley, W., DeVore, RF.[2015]

Induction chemotherapy with paclitaxel and carboplatin, followed by concurrent chemoradiation, showed a 55% response rate and a 1-year survival rate of 72% in patients with locally advanced non-small cell lung cancer, indicating promising efficacy.

The treatment regimen was well-tolerated, with mild myelotoxicity as the primary side effect from induction therapy and limited nonhematologic toxicity during concurrent therapy, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiation using paclitaxel and carboplatin in locally advanced non-small cell lung cancer. Langer, CJ.[2015]

In a study of 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

Combined chemotherapy with paclitaxel and carboplatin alongside thoracic radiation therapy has shown a clear survival benefit for patients with locally advanced, unresectable non-small cell lung cancer (NSCLC), as demonstrated in randomized trials and meta-analyses.

Ongoing and planned multicenter studies aim to refine treatment regimens and improve both local and systemic control of NSCLC, highlighting the need for a multidisciplinary approach to effectively manage this systemic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporation of paclitaxel and carboplatin in combined-modality therapy for locally advanced non-small cell lung cancer. Belani, CP.[2015]

The combination of paclitaxel and carboplatin followed by thoracic radiation therapy (TRT) has shown promising efficacy in treating locally advanced non-small-cell lung cancer (NSCLC), with a 60% partial response rate to combined therapy and a median survival of 15.3 months for all patients.

The treatment was well-tolerated, with manageable side effects, and the chemotherapy doses were safely escalated, indicating that this approach can be an effective option for patients with locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction and concurrent paclitaxel/carboplatin every 3 weeks with thoracic radiotherapy in locally advanced non-small-cell lung cancer: an interim report. Movsas, B., Hudes, RS., Schol, J., et al.[2019]

In a phase II study involving 23 previously untreated patients with stages IIIA or IIIB non-small cell lung cancer, the combination of paclitaxel, carboplatin, and concurrent radiation achieved a high overall response rate of 82%.

The treatment was associated with manageable toxicity, primarily esophagitis, affecting 45% of patients, but most recovered quickly, indicating that this regimen is a promising option for locally advanced lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin and concurrent radiation therapy for patients with locally advanced non-small cell lung cancer. Choy, H., Akerley, W., Safran, H., et al.[2015]

Citations

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First-line nab-paclitaxel plus carboplatin for patients with ... The NEPTUN study evaluated effectiveness and safety of first-line nab-paclitaxel (Abraxane) plus carboplatin (nab-P/C) in patients with advanced NSCLC in ...

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Carboplatin, Weekly Paclitaxel and Pembrolizumab in ... Carboplatin, weekly Paclitaxel (CwP) and Pembrolizumab is feasible in patients aged ≥70 with stage IV NSCLC and PD-L1 < 50%.

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Paclitaxel–Carboplatin Alone or with Bevacizumab for Non ... The median survival was 8 months, with no significant differences in overall survival among the groups. Although modest progress has been made with the use of ...

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Efficacy Comparison Between Weekly and Triweekly ... We demonstrated that weekly CP treatment, which is known to have fewer toxicity in NSCLC, provided better PFS compared to triweekly treatment.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12206876/

Real-world safety of carboplatin in non-small cell lung cancer The most reliable method to investigate carboplatin's intrinsic safety profile would be to analyze data from cases where carboplatin was ...

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Safety outcomes in advanced non-small-cell lung cancer ... We analyzed the treatment patterns and safety outcomes of the most common first-line platinum-based regimens initiated on or after non-small cell lung cancer ( ...

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Efficacy and safety of carboplatin with nab-paclitaxel ... Our study showed that overall survival was longer with carboplatin plus nab-paclitaxel than with docetaxel, suggesting that carboplatin plus nab-paclitaxel can ...