Atezolizumab + Chemoradiation for Small Cell Lung Cancer

Recruiting at 577 trial locations

Overseen By Stephen G. Chun

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Platinum/etoposide chemotherapy

Must not be taking: Immunotherapy, corticosteroids

Disqualifiers: Metastatic disease, autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 20

544 Participants Needed

Trial Summary

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, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the study treatment.

What data supports the effectiveness of the drug Atezolizumab combined with chemotherapy for small cell lung cancer?

Research shows that adding Atezolizumab to chemotherapy with carboplatin and etoposide significantly improved survival in patients with extensive-stage small cell lung cancer, without negatively affecting their quality of life. ^{1 2 3 4 5}

Is the combination of atezolizumab, chemotherapy, and radiation therapy generally safe for humans?

Research shows that the combination of atezolizumab with chemotherapy (carboplatin and etoposide) and radiation therapy has been studied for safety in patients with small cell lung cancer and other conditions. In a study, patients experienced some severe blood-related side effects, but these were managed by adjusting medication doses, and no severe non-blood-related side effects were reported. Overall, this combination has been considered safe for use in humans, with careful monitoring and dose adjustments as needed. ^{6 7 8 9 10}

What makes the treatment with Atezolizumab and Chemoradiation unique for small cell lung cancer?

This treatment combines atezolizumab, an immune checkpoint inhibitor, with chemotherapy and advanced radiation techniques like 3D-CRT and IMRT, offering a novel approach that enhances survival outcomes for extensive-stage small cell lung cancer compared to chemotherapy alone. ^{5 6 11 12 13}

What is the purpose of this trial?

This phase III trial studies how well chemotherapy and radiation therapy (chemoradiation) with or without atezolizumab works in treating patients with limited stage small cell lung cancer. Drugs used in chemotherapy, such as etoposide, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving chemoradiation with or without atezolizumab may work better in treating patients with limited stage small cell lung cancer.

Research Team

Kristin A Higgins

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for adults with a confirmed diagnosis of limited stage small cell lung cancer. Participants must have had one cycle of specific chemotherapy, be in good physical condition (ECOG 0-2), and have proper organ function. Pregnant women, those with certain medical conditions or previous treatments like immunotherapy, and individuals not using contraception are excluded.

Inclusion Criteria

Your liver function tests showed AST and ALT levels within a certain range before the start of the study.

Your total bilirubin level was not higher than 1.5 times the normal limit before starting the study.

My kidney function, measured by creatinine clearance, is adequate.

Exclusion Criteria

I've had radiation to my chest area that overlaps with new treatment areas.

You have fluid around your lungs or heart that has tested positive for abnormal cells.

I have an active hepatitis B or C infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Patients receive etoposide and cisplatin or carboplatin with radiation therapy. Cycles repeat every 21 days for 3 cycles.

9 weeks

Multiple visits for chemotherapy and radiation sessions

Immunotherapy

Patients receive atezolizumab IV on day 1 or 2 of each chemotherapy cycle. Cycles repeat every 3 weeks for 17 cycles.

1 year

17 visits for immunotherapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, then every 6 months for 3 years, then annually

Treatment Details

Interventions

• 3-Dimensional Conformal Radiation Therapy
• Atezolizumab
• Carboplatin
• Cisplatin
• Etoposide
• Intensity-Modulated Radiation Therapy

Trial Overview The study is examining the effectiveness of adding Atezolizumab to standard chemoradiation therapy for treating small cell lung cancer. It compares outcomes between patients receiving usual treatment alone versus those also getting this new immunotherapy drug.

Participant Groups

Group I: Arm II (chemotherapy, radiation therapy, atezolizumab) Experimental Treatment 9 Interventions

Patients receive treatment as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 or 2 of each chemotherapy cycle. Cycles repeat every 3 weeks for 17 cycles (1 year) in the absence of disease progression or unacceptable toxicity. Patients undergo blood specimen collection throughout the trial.

Group II: Arm I (chemotherapy, radiation therapy) Active Control 8 Interventions

Patients receive etoposide IV on days 1-3 and cisplatin IV or carboplatin IV on day 1. Cycles repeat every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo 3D-CRT or IMRT BID for approximately 3 weeks or QD for approximately 6-7 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood specimen collection throughout the trial.

3-Dimensional Conformal Radiation Therapy is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in European Union as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Canada as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Japan as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in China as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Switzerland as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Findings from Research

In a study of 90 patients with limited stage small cell lung cancer, concurrent radiotherapy combined with carboplatin and etoposide significantly improved median survival time to 26 months compared to 19 months for those receiving sequential treatment.

The 5-year survival rate was also better in the concurrent treatment group at 27%, versus 16% in the sequential group, indicating that concurrent treatment may be a more effective approach for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Concurrent radiotherapy combined with carboplatin and etoposide in limited stage small cell lung cancer]. Qiao, TK., Zhou, DA., Xin, L., et al.[2016]

In a study of 47 patients with limited disease small-cell lung carcinoma, the combination of carboplatin and etoposide followed by thoracic radiotherapy resulted in a 73% overall response rate, but the median survival time was only 13.7 months, indicating limited long-term efficacy.

The treatment was associated with significant adverse effects, including grade 3-4 neutropenia in 46% of patients and febrile neutropenia in 14%, highlighting safety concerns despite the initial response to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and etoposide followed by once-daily thoracic radiotherapy in limited disease small-cell lung cancer: unsatisfactory results. Yilmaz, U., Anar, C., Korkmaz, E., et al.[2022]

In a study of 108 patients with extensive-stage small-cell lung cancer, the combination of irinotecan + cisplatin (IP) sequential chemotherapy with radiotherapy showed significantly better efficacy compared to etoposide + cisplatin (EP) chemotherapy, resulting in higher overall survival (16.2 months vs. 12.7 months) and progression-free survival (8.4 months vs. 5.9 months).

The EP+IP group also demonstrated a significant reduction in serum tumor markers and circulating tumor cells, indicating a more effective treatment response and potentially fewer blood-related side effects compared to the EP group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of EP Chemotherapy Followed by IP Chemotherapy Combined with Radiotherapy in the Treatment of Extensive-Stage Small-Cell Lung Cancer. Kang, S., Lai, CORXWZJHYZDCJ.[2021]

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]

An 80-year-old male with extensive-stage small cell lung cancer safely received a combination of carboplatin, etoposide, and atezolizumab while undergoing hemodialysis, indicating that this treatment can be feasible for patients with similar conditions.

Despite experiencing grade 4 neutropenia and leukopenia during the first cycle, the patient was able to continue treatment with adjusted dosages, and no severe non-haematological adverse events were reported after four cycles, demonstrating a positive response to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy plus atezolizumab for a patient with small cell lung cancer undergoing haemodialysis: a case report and review of literature. Imaji, M., Fujimoto, D., Kato, M., et al.[2021]

In a phase 2 study involving 45 patients with invasive bladder cancer, the combination of radiation therapy and atezolizumab resulted in a high pathologic complete response (pCR) rate of 84.4%, particularly in older patients and those with high PD-L1 expression.

The treatment was associated with acceptable toxicity, with 93.3% of patients experiencing adverse events, mostly mild to moderate, and only 13.3% experiencing grade 3 adverse events, indicating that this approach could be a viable bladder-preserving option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. Kimura, T., Ishikawa, H., Nagumo, Y., et al.[2023]

In the IMpower133 study involving 394 patients with extensive-stage small-cell lung cancer, the addition of atezolizumab to carboplatin and etoposide significantly improved progression-free and overall survival without increasing the overall safety risks compared to the placebo.

While immune-related adverse events were more common in the atezolizumab group, the overall safety profile was comparable to the placebo, and patient-reported quality of life improved more significantly in the atezolizumab group, supporting its use as a new standard of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Mansfield, AS., Każarnowicz, A., Karaseva, N., et al.[2022]

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]

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 the phase III SKYSCRAPER-02 study involving 490 patients with untreated extensive-stage small-cell lung cancer, the addition of tiragolumab to atezolizumab and chemotherapy did not significantly improve progression-free survival (PFS) or overall survival (OS).

The combination treatment was well tolerated, with similar rates of immune-mediated adverse events between the tiragolumab and control groups, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. Rudin, CM., Liu, SV., Soo, RA., et al.[2023]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

[Concurrent radiotherapy combined with carboplatin and etoposide in limited stage small cell lung cancer]. [2016]

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

Carboplatin and etoposide followed by once-daily thoracic radiotherapy in limited disease small-cell lung cancer: unsatisfactory results. [2022]

3. England pubmed.ncbi.nlm.nih.gov

A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. [2020]

4. Cyprus pubmed.ncbi.nlm.nih.gov

Efficacy of EP Chemotherapy Followed by IP Chemotherapy Combined with Radiotherapy in the Treatment of Extensive-Stage Small-Cell Lung Cancer. [2021]

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

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

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

Chemotherapy plus atezolizumab for a patient with small cell lung cancer undergoing haemodialysis: a case report and review of literature. [2021]

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

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. [2023]

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

Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. [2022]

9. 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]

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

Phase I Trial of Pembrolizumab and Radiation Therapy after Induction Chemotherapy for Extensive-Stage Small Cell Lung Cancer. [2023]

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

SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. [2023]

12. United States 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. [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. [2023]