Atezolizumab + Chemoradiation for Small Cell Lung Cancer

Not currently recruiting at 599 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of chemotherapy and radiation with or without a new treatment called atezolizumab for small cell lung cancer. Chemotherapy uses drugs to kill cancer cells, while radiation employs high-energy rays to shrink tumors. Atezolizumab, an immunotherapy, helps the immune system attack cancer cells. The trial seeks participants diagnosed with small cell lung cancer that hasn't spread beyond the lungs and who have already started chemotherapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that atezolizumab is generally well-tolerated by people with small cell lung cancer. In past studies, most patients managed the treatment well, though some experienced side effects. For instance, about 3% of patients had immune-related lung issues.

Atezolizumab is already used with chemotherapy for other types of small cell lung cancer, supporting its safety. Most people can handle the treatment, but it might cause some side effects. Always consult a healthcare provider about the risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about adding atezolizumab to the standard treatment for small cell lung cancer because it introduces a new mechanism of action. Unlike traditional treatments, which typically involve chemotherapy and radiation, atezolizumab is an immunotherapy drug that helps the immune system recognize and attack cancer cells. This approach could potentially enhance the effectiveness of existing therapies, improving patient outcomes by potentially extending survival and reducing the likelihood of cancer progression. The combination of immunotherapy with chemotherapy and radiation is a promising development in the fight against this aggressive cancer type.

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

Research has shown that adding atezolizumab to chemotherapy for small cell lung cancer can extend patient survival. In this trial, participants in Arm II will receive atezolizumab combined with chemotherapy and radiation therapy. One study found that patients who received atezolizumab with chemotherapy lived an average of 12.3 months, compared to those who did not receive the drug. Another study found that this combination also delayed cancer progression, with patients living an average of 5.2 months without their cancer worsening. This treatment has proven effective in both clinical trials and real-world settings for people with extensive-stage small cell lung cancer. These findings suggest that atezolizumab may enhance the immune system's ability to fight cancer, offering hope for patients with limited-stage small cell lung cancer. ^{2 3 4 5 6}

Who Is on the Research Team?

Kristin A Higgins

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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]

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]

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]

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]

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 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]

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]

Citations

1. tecentriq-hcp.com tecentriq-hcp.com/sclc/efficacy/clinical-trial-results.html

IMpower133 efficacy results in 1L ES-SCLC Adding TECENTRIQ® (atezolizumab) to carbo/etop significantly improved median PFS1. 5.2-month median PFS vs 4.3 months with placebo + carbo/etop (HR=0.77*; ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37871898/

The Real-World Outcome of First Line Atezolizumab in ... We provided evidence of the favorable real-world effectiveness and safety of atezolizumab plus chemotherapy in ES-SCLC patients.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1809064

First-Line Atezolizumab plus Chemotherapy in Extensive- ... Despite response rates of 60 to 65%, limited progress has been made in more than two decades; outcomes remain poor, with a median overall ...

4. tecentriq.com tecentriq.com/sclc/results/how-tecentriq-may-help.html

Imagine if you had more time to live your life More patients lived longer with TECENTRIQ + chemotherapy ... Median overall survival (OS) was 12.3 months for patients taking TECENTRIQ® (atezolizumab.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0169500223009170

Results of the IFCT-1905 CLINATEZO real-world study Atezolizumab plus chemotherapy improves overall survival in 1st-line treatment of extensive SCLC. IFCT-1905 CLINATEZO studied consecutive patients receiving ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31959349/

Safety and Patient-Reported Outcomes of Atezolizumab ... These data demonstrate the positive benefit-risk profile of first-line atezolizumab plus CP/ET in ES-SCLC and further support this regimen as a new standard of ...