Radiation + Chemo-immunotherapy for Small Cell Lung Cancer

Overseen By Research Nurse Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brian Henick, MD

Must not be taking: Denosumab, Immunosuppressants, others

Disqualifiers: Active CNS metastases, Autoimmune disease, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

2 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding radiation therapy to standard chemo-immunotherapy can improve treatment for people with extensive stage small cell lung cancer (ES-SCLC) that has spread to the liver. The current standard treatment involves chemotherapy drugs and an immunotherapy called atezolizumab (Tecentriq), but it is less effective when the cancer involves the liver. The trial aims to determine if targeting liver metastases with radiation can enhance the effectiveness of the existing treatment. Participants will receive a combination of chemotherapy, immunotherapy, and radiation. This trial may suit those who have never been treated for ES-SCLC and have at least one liver metastasis. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on denosumab, you must be willing to switch to a bisphosphonate. Also, you cannot be on systemic immunosuppressive medications within 2 weeks prior to randomization, except for certain low-dose or inhaled corticosteroids. It's best to discuss your specific medications with the trial team.

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

Studies have shown that the combination of atezolizumab, carboplatin, and etoposide is generally well-tolerated in patients with advanced small-cell lung cancer. Adding atezolizumab to chemotherapy has extended survival for many patients without causing significant additional side effects. Most patients experience side effects such as tiredness, nausea, and low blood counts, which are common with chemotherapy and can usually be managed.

The researchers are also examining the safety of adding radiation therapy, specifically targeting cancer that has spread to the liver. While radiation might increase side effects like tiredness or discomfort in the treated area, these treatments have been used safely in other contexts.

In summary, based on existing research, the current treatment combination is considered safe, and the trial is carefully designed to monitor any new risks from adding radiation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about this treatment for small cell lung cancer because it combines standard chemotherapy and immunotherapy with a unique approach: liver-directed stereotactic body radiation therapy (SBRT). While traditional treatments focus on broad systemic effects, this method precisely targets liver metastases, potentially improving outcomes by directly addressing cancer spread. The addition of SBRT could enhance the effectiveness of the standard care, offering a more tailored and potentially more powerful way to combat the disease.

What evidence suggests that adding radiation to chemo-immunotherapy could be effective for small cell lung cancer with liver metastases?

Research has shown that combining the drugs atezolizumab, carboplatin, and etoposide extends the lives of patients with extensive-stage small cell lung cancer (ES-SCLC). In this trial, participants will receive this standard treatment, with some also receiving additional radiation therapy targeting the liver. Early results suggest that this extra radiation, known as Stereotactic Body Radiation Therapy (SBRT), could improve outcomes by directly targeting cancer that has spread to the liver. ^{1 6 7 8 9}

Who Is on the Research Team?

Brian Henick, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for adults with extensive stage small cell lung cancer (ES-SCLC) that has spread to the liver. They should not have had previous treatments for ES-SCLC, must be in good physical condition (ECOG 0 or 1), and cannot be on steroids for brain metastases. Participants need at least one liver tumor of a certain size and must provide a tissue sample before treatment starts. Women who can bear children and men must agree to use contraception.

Inclusion Criteria

My blood and organ tests meet the required health standards.

I have not received any treatment for small cell lung cancer.

I have a cancer that can be measured by scans, besides the liver cancer being treated with SBRT.

Exclusion Criteria

I am not pregnant, breastfeeding, nor planning to become pregnant during the study.

I have previously been treated with immune checkpoint inhibitors.

I have high calcium levels in my blood that are causing symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chemo-immunotherapy with atezolizumab, carboplatin, and etoposide, along with liver-directed stereotactic body radiation therapy (SBRT)

6 months

Regular visits as per standard of care

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Carboplatin
• Etoposide
• Stereotactic Body Radiation Therapy (SBRT)

Trial Overview The study tests if adding radiation therapy targeting liver tumors improves outcomes when combined with standard chemo-immunotherapy (carboplatin, etoposide, atezolizumab) in patients with ES-SCLC that has spread to the liver. All participants will receive both chemo-immunotherapy and stereotactic body radiation therapy.

How Is the Trial Designed?

Group I: Experimental: Chemotherapy+SBRT Experimental Treatment 4 Interventions

Addition of SBRT, directed at liver metastases, to standard of care (SOC) treatment atezolizumab+chemotherapy in SCLC. All patients must undergo a mandatory biopsy of a liver lesion prior to chemotherapy initiation. Cycle 1 of chemoimmunotherapy will be administered as per standard of care, with radiation planning to be done subsequently in anticipation of liver-directed SBRT.

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Brian Henick, MD

Lead Sponsor

Trials

2

Recruited

10+

Published Research Related to This Trial

In a study of 65 patients with extensive-disease small-cell lung cancer, the combination of atezolizumab, carboplatin, and etoposide showed a high response rate of 73.8%, with 80.5% in elderly patients (median age 74 years).

Despite some significant hematological toxicities, such as decreased neutrophil counts in 61.1% of elderly patients, the treatment demonstrated acceptable safety and efficacy, suggesting it could be a preferred standard treatment for elderly patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data of atezolizumab plus carboplatin and etoposide in elderly patients with extensive-disease small-cell lung cancer. Shiono, A., Imai, H., Wasamoto, S., et al.[2023]

Combining PD-1/PD-L1 inhibitors with chemotherapy significantly improves overall survival (OS) and progression-free survival (PFS) in patients with extensive-stage small-cell lung cancer (ES-SCLC), based on an analysis of six randomized controlled trials involving 2600 patients.

Among the combinations studied, serplulimab plus chemotherapy showed the best outcomes for OS, PFS, and objective response rate (ORR), while PD-1 inhibitors demonstrated a notable advantage in PFS compared to PD-L1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first-line PD-1/PD-L1 inhibitor combinations for extensive-stage small-cell lung cancer: a Bayesian network meta-analysis. Li, H., Han, H., Li, C., et al.[2023]

In a phase I trial involving 38 patients with extensive-stage small cell lung cancer, the combination of pembrolizumab and thoracic radiotherapy was found to be safe, with no dose-limiting toxicities observed in the first 35 days of treatment.

The median progression-free survival was 6.1 months and overall survival was 8.4 months, suggesting that while the safety profile is promising, further studies are needed to fully understand the efficacy of this combined treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Pembrolizumab and Radiation Therapy after Induction Chemotherapy for Extensive-Stage Small Cell Lung Cancer. Welsh, JW., Heymach, JV., Chen, D., et al.[2023]

In a study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

In a phase 3 trial with 572 patients, atezolizumab significantly improved overall survival by 7.1 months compared to platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC) and high PD-L1 expression (20.2 months vs. 13.1 months).

Atezolizumab also demonstrated a favorable safety profile, with fewer grade 3 or 4 adverse events (30.1%) compared to chemotherapy (52.5%), indicating it may be a safer first-line treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. Herbst, RS., Giaccone, G., de Marinis, F., et al.[2022]

The FDA approved atezolizumab, a PD-L1 inhibitor, in combination with carboplatin and etoposide as a first-line treatment for small cell lung cancer, highlighting its role in enhancing therapy options.

This approval was supported by the phase III IMpower133 trial, which demonstrated that the addition of atezolizumab significantly improved both overall survival and progression-free survival in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Atezolizumab OK'd for SCLC. [2020]

Atezolizumab, combined with carboplatin and etoposide, significantly improves overall survival and progression-free survival in patients with extensive-stage small cell lung cancer, based on data from the IMpower133 trial involving previously untreated patients.

The treatment regimen is generally well tolerated, with no new safety concerns identified, and it does not negatively impact patients' quality of life, making it a valuable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. Frampton, JE.[2021]

Atezolizumab combined with carboplatin and etoposide was effective in treating a 75-year-old woman with advanced small cell lung cancer and an ECOG Performance Status of 2, leading to complete regression after 4 cycles of treatment.

Despite experiencing some adverse effects like anemia and thrombocytopenia, the patient's therapy was continued due to positive imaging results, highlighting the potential for immunochemotherapy in patients typically excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 75-Year-Old Female Smoker with Advanced Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status 2 who Responded to Combination Immunochemotherapy with Atezolizumab, Etoposide, and Carboplatin. Dębczyński, M., Mojsak, D., Kuklińska, B., et al.[2022]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

In a study of 518 patients with extensive small cell lung cancer (SCLC) receiving atezolizumab plus chemotherapy, the median overall survival was 11.3 months, with 46.7% of patients alive at 12 months, indicating the treatment's effectiveness in a real-world setting.

The study demonstrated that 23.6% of patients continued atezolizumab treatment beyond disease progression, suggesting a potential strategy for improving outcomes, particularly in patients with better performance status (PS 0/1) who had a median overall survival of 12.2 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study. Falchero, L., Guisier, F., Darrason, M., et al.[2023]

The combination of atezolizumab, a PD-L1 inhibitor, with platinum-based chemotherapy significantly improves overall survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone.

This research suggests that this combination therapy could become a new first-line treatment option for patients suffering from this aggressive form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study: Atezolizumab Improves Survival in SCLC. [2019]

In a phase 2 trial involving 40 patients with extensive-stage small-cell lung cancer (ES-SCLC), the combination of atezolizumab with carboplatin/cisplatin and etoposide, along with concurrent hypofractionated radiotherapy, was well tolerated with manageable adverse effects, including a pneumonitis rate of 12.5%.

The treatment showed promising efficacy with a median progression-free survival (PFS) of 8.6 months, suggesting that this combination could be an effective first-line therapy for ES-SCLC, although further randomized trials are necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy with immunochemotherapy for extensive-stage small-cell lung cancer. Liu, C., Zeng, L., Deng, C., et al.[2023]

Citations

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Liver Directed RT + Chemo-immunotherapy for ES-SCLC The purpose of this study is to evaluate whether radiation treatment directed at liver metastases can be safely added to standard of care treatment for ...

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