Radiation Therapy + Atezolizumab for Small Cell Lung Cancer

Recruiting at 414 trial locations

Overseen By Nataniel H. Lester-Coll

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Atezolizumab

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune disease, Liver 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

Duration: 5 weeks

138 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II/III trial compares the effect of adding radiation therapy to the usual maintenance therapy with atezolizumab versus atezolizumab alone in patients who have already received atezolizumab plus chemotherapy for the treatment of small cell lung cancer that has spread outside of the lung or to other parts of the body (extensive stage). 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. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radiation therapy in addition to atezolizumab may extend the time without extensive small cell lung cancer growing or spreading compared to atezolizumab alone.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on immunosuppressive treatments or steroids above a certain dose, you may not be eligible. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Radiation Therapy + Atezolizumab for Small Cell Lung Cancer?

Research shows that adding atezolizumab to chemotherapy for extensive-stage small cell lung cancer (ES-SCLC) significantly improves survival outcomes compared to chemotherapy alone. Additionally, combining radiotherapy with immunotherapy like atezolizumab may enhance the body's immune response against tumors. ^{1 2 3 4 5}

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

The combination of atezolizumab and radiation therapy has been studied in various trials and is generally well tolerated in humans. In a phase I trial for non-small cell lung cancer, the treatment was well tolerated, and the maximum tolerated dose of atezolizumab was established. Additionally, a study on bladder cancer also evaluated the safety of this combination, indicating it is safe for use in humans. ^{1 3 4 6 7}

How is the treatment of radiation therapy combined with the drug atezolizumab unique for small cell lung cancer?

This treatment is unique because it combines atezolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with radiation therapy, which may enhance the immune response against the tumor. This combination aims to improve outcomes for patients with small cell lung cancer by leveraging the potential synergistic effects of both therapies. ^{3 4 5 7 8}

Research Team

Quynh-Nhu Nguyen

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for adults with extensive stage small cell lung cancer who've had some success (partial response or stable disease) after initial treatment with chemotherapy and Atezolizumab. They should have a good performance status, controlled HIV if present, no more than three liver metastases, and adequate organ function. Pregnant women, those with severe other diseases or conditions that could affect the trial's outcomes are excluded.

Inclusion Criteria

Study-specific informed consent provided by patient or legally authorized representative

My small cell lung cancer is confirmed and has spread.

I have had whole brain radiation for my brain metastases.

Exclusion Criteria

My autoimmune disease has been inactive for over 3 years or is under stable treatment.

I do not have recent heart issues or significant lung disease.

I have a condition that weakens my immune system or COPD needing long-term oral steroids.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab intravenously every 21 days, with or without radiation therapy for 5 weeks

5 weeks

Weekly visits for radiation therapy, every 21 days for atezolizumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years

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

Treatment Details

Interventions

• Atezolizumab
• Radiation Therapy

Trial Overview The RAPTOR trial is examining whether adding radiation therapy to standard immune therapy (Atezolizumab) improves outcomes in patients with extensive stage small cell lung cancer. It's a phase II/III study comparing the effects of combined radiation and Atezolizumab versus Atezolizumab alone after initial successful treatment.

Participant Groups

Group I: Arm II (atezolizumab, radiation therapy) Experimental Treatment 6 Interventions

Patients receive atezolizumab IV over 30 minutes +/- 10 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo radiation therapy QD on days 1-5 during weeks 1-5 only. Patients undergo PET/CT scan, CT, and MRI throughout the trial. Patients also undergo blood and tissue collection throughout the trial.

Group II: Arm I (atezolizumab) Active Control 5 Interventions

Patients receive atezolizumab IV over 30 minutes +/- 10 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT scan, CT, and MRI throughout the trial. Patients also undergo blood and tissue collection throughout the trial.

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?

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 phase I study involving 20 patients with early-stage non-small cell lung cancer, the combination of stereotactic ablative radiotherapy (SABR) and the immune-checkpoint inhibitor atezolizumab was well tolerated, with the maximum tolerated dose established at 1200 mg.

Early efficacy signals were observed, with 17% of patients showing responses after two cycles of atezolizumab before starting SABR, and specific biomarkers indicating T cell activation were found to be predictive of treatment benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. Monjazeb, AM., Daly, ME., Luxardi, G., 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]

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]

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]

In a pilot study involving 12 patients with metastatic non-small cell lung cancer, the combination of hypofractionated image-guided radiation therapy (HIGRT) and atezolizumab achieved a disease control rate of 50%, with a partial response in 3 patients.

The treatment was associated with a median overall survival of 6.9 months and a median progression-free survival of 2.3 months, with the incidence of grade 3 adverse events being similar to that of atezolizumab alone, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of Atezolizumab Plus Hypofractionated Image Guided Radiation Therapy for the Treatment of Advanced Non-Small Cell Lung Cancer. Qin, A., Rengan, R., Lee, S., et al.[2021]

Immunotherapy with atezolizumab and durvalumab has significantly improved median overall survival in small cell lung cancer patients by more than 2 months, marking a major advancement in treatment after decades of stagnation.

These immunotherapies, when combined with chemotherapy, have established a new gold standard for treating small cell lung cancer without significantly increasing treatment toxicity or negatively impacting patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the therapy of small cell lung cancer. Vrána, D.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

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

3. 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]

4. 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]

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

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

6. 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]

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

A Pilot Study of Atezolizumab Plus Hypofractionated Image Guided Radiation Therapy for the Treatment of Advanced Non-Small Cell Lung Cancer. [2021]

8. Czech Republic pubmed.ncbi.nlm.nih.gov

Advances in the therapy of small cell lung cancer. [2021]