Durvalumab + Radiation for Small Cell Lung Cancer

Recruiting at 1 trial location

Overseen By Cancer Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must not be taking: Immunosuppressants, others

Disqualifiers: Autoimmune disorders, Active infection, 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

Duration: 12 weeks

49 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating extensive-stage small cell lung cancer that hasn't responded to previous treatments. Researchers aim to determine if adding targeted radiation (ablative radiation) to a combination of durvalumab (an immunotherapy), carboplatin, and etoposide (both chemotherapy drugs) can extend the time patients live without their cancer worsening. Individuals diagnosed with extensive-stage small cell lung cancer who haven't received prior treatment may be suitable candidates. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take other cancer treatments or immunosuppressive medications within 14 days before starting the trial.

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

Research has shown that durvalumab is safe for use in many types of solid cancers. When combined with other treatments, it generally causes manageable side effects. Most patients tolerate it well, with few serious side effects reported. The FDA approved durvalumab for use with chemotherapy in treating small cell lung cancer, suggesting its general safety in this setting.

The radiation used in this study is stereotactic ablative radiotherapy (SABR). Studies indicate that SABR has low toxicity rates, meaning most people experience only mild side effects.

In summary, both durvalumab and the specific type of radiation used have been shown to be safe for many patients. While some mild side effects may occur, serious issues seem rare, indicating the treatment is well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for small cell lung cancer because it combines immunotherapy with radiation to potentially boost effectiveness. Unlike standard treatments that typically rely on chemotherapy alone, this approach uses durvalumab, an immunotherapy drug, to help the body's immune system target cancer cells more effectively. Additionally, integrating ablative radiation during the chemotherapy cycles might enhance the treatment's ability to shrink tumors quickly. This combination could offer a more comprehensive attack on cancer cells, potentially improving outcomes for patients with extensive small cell lung cancer.

What evidence suggests that adding radiation to durvalumab and chemotherapy could be effective for small cell lung cancer?

Research has shown that durvalumab, when combined with chemotherapy, yields promising results for treating extensive-stage small cell lung cancer (ES-SCLC). Studies have found that adding durvalumab to standard chemotherapy can extend the lives of patients with ES-SCLC. Some data even suggest that this combination can help some patients survive for three years or more.

In this trial, all participants will receive a combination of durvalumab, carboplatin, and etoposide, along with ablative radiation therapy. This focused radiation effectively controls tumors with few side effects, precisely targeting the cancer and reducing harm to nearby healthy tissue. Using these treatments together may enhance their effectiveness, potentially helping patients live longer without their cancer worsening. ^{1 2 3 6 7}

Who Is on the Research Team?

Christine M. Bestvina

Principal Investigator

University of Chicago - Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed extensive-stage small cell lung cancer that hasn't been treated yet. Participants must have a life expectancy of at least 12 weeks, be able to perform daily activities (ECOG status 0-2), and have tumors suitable for focused radiation. They should not be pregnant or breastfeeding, agree to use contraception, and cannot have had previous treatments like chemotherapy or certain immunotherapies for lung cancer.

Inclusion Criteria

I weigh more than 30 kilograms.

I am eligible for platinum-based chemotherapy as my first treatment for extensive small cell lung cancer.

You are expected to live for at least 12 more weeks.

Exclusion Criteria

I am not pregnant or breastfeeding and willing to use birth control during and up to 90 days after treatment.

You have had an organ transplant from someone else.

Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to four 21-day cycles of chemotherapy with carboplatin, etoposide, and durvalumab, with ablative radiation added during the second cycle

12 weeks

Maintenance

Participants continue to receive a fixed dose of durvalumab until disease progression, serious side effects, or withdrawal from the study

Up to 48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Ablative Radiation
• Carboplatin
• Durvalumab
• Etoposide

Trial Overview The study tests if adding ablative radiation therapy to the FDA-approved combination of durvalumab (an immunotherapy drug), carboplatin, and etoposide can improve survival without cancer progression in patients with extensive-stage small cell lung cancer. The treatment's effectiveness will be monitored over approximately four years.

How Is the Trial Designed?

Group I: Participants With Extensive Small Cell Lung Cancer (All Participants) Experimental Treatment 4 Interventions

This arm will involve all participants in the study who have extensive small cell lung cancer that has not responded to previous treatments. All participants will receive the same treatment of study drugs and radiation treatment in "cycles" (a specific window of time). You will receive up to four 21-day cycles of chemotherapy using carboplatin, etoposide and durvalumab (immunotherapy) as part of a standard care treatment plan recommended by your doctor. These drugs will be combined with ablative radiation treatment during the second cycle of chemotherapy. After completing these four cycles of chemotherapy (with radiation treatment added in cycle 2), you will continue to receive a fixed dose of durvalumab until your cancer progresses, you experience serious side effects, you decide to no longer be part of the study or the study doctor request to take you off the study for medical reasons.

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?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In the phase III CASPIAN trial involving previously untreated adults with extensive-stage small cell lung cancer (ES-SCLC), the addition of durvalumab to chemotherapy significantly improved overall survival and progression-free survival compared to chemotherapy alone.

Durvalumab combined with etoposide and either carboplatin or cisplatin demonstrated a manageable safety profile, making it a valuable first-line treatment option and an accepted standard of care for patients with ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: A Review in Extensive-Stage SCLC. Al-Salama, ZT.[2022]

In the phase III CASPIAN study, the combination of durvalumab with etoposide and either cisplatin or carboplatin significantly improved overall survival in patients with extensive-stage small-cell lung cancer compared to etoposide plus platinum alone.

Patient-reported outcomes showed that the addition of durvalumab not only maintained quality of life but also delayed the worsening of key symptoms like appetite loss, cough, and fatigue, indicating a beneficial impact on patients' overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Goldman, JW., Garassino, MC., Chen, Y., et al.[2021]

In a Phase II trial involving 74 patients with unresectable, locally advanced non-small cell lung cancer (NSCLC), durvalumab immunotherapy combined with radiotherapy resulted in a promising 12-month progression-free survival (PFS) rate of 72.1%, indicating its efficacy as a treatment option.

The treatment was generally well-tolerated, with a high objective response rate of 90.9%, although 52.9% of patients experienced severe adverse events (grade 3 or 4), highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab Plus Concurrent Radiotherapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Phase 2 Nonrandomized Controlled Trial. Tachihara, M., Tsujino, K., Ishihara, T., et al.[2023]

In the CASPIAN study involving 805 patients with extensive-stage small-cell lung cancer (ES-SCLC), the combination of durvalumab and platinum-etoposide significantly improved overall survival compared to platinum-etoposide alone, with a median survival of 12.9 months versus 10.5 months.

However, adding tremelimumab to durvalumab and platinum-etoposide did not provide a significant survival benefit, indicating that durvalumab plus platinum-etoposide should be considered the new standard of care for first-line treatment of ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Goldman, JW., Dvorkin, M., Chen, Y., et al.[2021]

Durvalumab, used as a consolidation treatment for locally advanced PD-L1-positive non-small cell lung cancer (NSCLC) after chemoradiotherapy, demonstrated comparable efficacy in terms of progression-free survival (20.1 months) and overall survival (not reached) to the results of the PACIFIC trial, even in a more advanced patient population.

The study found that durvalumab is safe and effective in real-world settings, with encouraging outcomes for selected stage IV patients and those with autoimmune diseases, suggesting that PD-L1 status should not exclude patients from receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab after definitive chemoradiotherapy in locally advanced unresectable non-small cell lung cancer (NSCLC): Real-world data on survival and safety from the German expanded-access program (EAP). Faehling, M., Schumann, C., Christopoulos, P., et al.[2021]

This study is investigating the combination of the anti-PD-L1 antibody durvalumab with carboplatin and etoposide in 56 previously untreated patients with extensive-stage small-cell lung cancer (ES-SCLC) and poor performance status (PS 2-3), aiming to assess its safety and efficacy.

The primary goal is to evaluate the tolerability of this treatment regimen, while secondary outcomes include survival rates and response to treatment, addressing a significant unmet medical need for patients with poor prognosis in ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of carboplatin and etoposide plus durvalumab for previously untreated extensive-stage small-cell lung cancer (ES-SCLC) patients with a poor performance status (PS): NEJ045A study protocol. Asao, T., Watanabe, S., Tanaka, T., et al.[2022]

The DUART trial is a Phase II study investigating the safety and tolerability of durvalumab in patients with unresectable, stage III non-small-cell lung cancer (NSCLC) who cannot undergo chemotherapy due to poor performance status or other health issues.

This study aims to evaluate whether durvalumab can improve survival outcomes for these patients compared to the current standard of care, which is radiotherapy alone, based on promising results from the PACIFIC trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. Filippi, AR., Dziadziuszko, R., García Campelo, MR., et al.[2022]

Durvalumab has been approved for use in patients with locally advanced PD-L1-positive non-small cell lung cancer (NSCLC) after chemoradiotherapy, based on its efficacy demonstrated in the PACIFIC trial and subsequent analysis of 211 patients in the Expanded Access Program (EAP).

In the EAP, 126 patients who received durvalumab were included, some of whom had oligometastatic disease and a history of autoimmune conditions, indicating that durvalumab may be effective and safe for a broader patient population than previously studied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab after definitive chemoradiotherapy in locally advanced NSCLC: Data of the German EAP. Faehling, M., Schumann, C., Christopoulos, P., et al.[2020]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

In the phase III CASPIAN study, durvalumab combined with etoposide and either cisplatin or carboplatin significantly improved overall survival in patients with extensive-stage small-cell lung cancer, with a median overall survival of 12.9 months compared to 10.5 months for the control group.

After more than 3 years of follow-up, durvalumab plus etoposide showed a 36-month overall survival rate of 17.6%, indicating that this combination is a promising first-line treatment option for extensive-stage small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. Paz-Ares, L., Chen, Y., Reinmuth, N., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10905608/

Multi-Institutional Experience of Stereotactic Ablative ... Stereotactic body radiation therapy (SBRT), also termed stereotactic ablative radiation therapy (SABR), results in high local control (LC) with minimal ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167814024007096

Stereotactic ablative radiotherapy for locally advanced non ... This meta-analysis presents promising findings regarding LC and OS rates, while also observing low toxicity rates, indicating the potential feasibility of SABR ...

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2823972

Stereotactic vs Hypofractionated Radiotherapy for ... In this randomized clinical trial, SBRT resulted in acceptable tumor control compared with CRT with limited toxic effects.

4. thegreenjournal.com thegreenjournal.com/article/S0167-8140(14)00541-6/fulltext

Management of early-stage non-small cell lung cancer ... Abstract. The use of stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer is growing rapidly, particularly since it has become ...

5. jto.org jto.org/article/S1556-0864(15)33037-9/fulltext

Stereotactic Ablative Radiation Therapy for the Treatment ... Stereotactic Ablative Radiation Therapy for the Treatment of Early-stage Non–Small-Cell Lung Cancer: CEPO Review and Recommendations. Gino Boily, PhD.

6. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2809582

Individualized Stereotactic Ablative Radiotherapy for Lung ... This nonrandomized controlled trial of patients diagnosed with non–small cell lung cancer assesses whether individualizing stereotactic ...

7. jto.org jto.org/article/S1556-0864(15)32359-5/fulltext

Stereotactic Ablative Radiotherapy for Centrally Located ... It has produced local control rates in excess of 90% for patients with early stage non–small-cell lung cancer (NSCLC) when the biological effective dose (BED) ...