Radiation + Immunotherapy for Non-Small Cell Lung Cancer

Recruiting at 184 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Steroids, Live vaccines

Disqualifiers: Active infection, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 38

47 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the side effects of radiation therapy followed by atezolizumab in treating patients with stage II or III non-small cell lung cancer. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more cancer cells and have fewer side effects. 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. The purpose of this study is to test the safety and effectiveness of radiation therapy followed by atezolizumab and find out what side effects, if any, it has on patient's non-small cell lung cancer.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you must not have received steroids in doses higher than prednisone 10 mg daily within 14 days before starting Step 2 of the trial.

What data supports the effectiveness of the treatment Atezolizumab, Tecentriq, Hypofractionated Radiation Therapy, Hypofractionated Radiotherapy, HFRT for Non-Small Cell Lung Cancer?

Research shows that hypofractionated radiation therapy (HFRT) can improve local control and shorten treatment time for inoperable non-small cell lung cancer (NSCLC). Additionally, combining radiation with immunotherapy, like PD-1 targeting drugs, may enhance the immune response against tumors. ^{1 2 3 4 5}

Is the combination of radiation and immunotherapy safe for treating non-small cell lung cancer?

Studies have shown that hypofractionated radiation therapy (HFRT) is generally well tolerated, but it may increase the risk of gastrointestinal (GI) or genitourinary (GU) side effects. More research is needed to fully understand the safety of combining HFRT with immunotherapy in lung cancer. ^{3 5 6 7 8}

How is hypofractionated radiation therapy (HFRT) different from other treatments for non-small cell lung cancer?

Hypofractionated radiation therapy (HFRT) is unique because it delivers higher doses of radiation over a shorter period, potentially improving local control and reducing treatment time. When combined with immunotherapy, it may enhance the immune response against tumors, offering a novel approach compared to traditional treatments. ^{1 2 3 4 9}

Research Team

Raid Aljumaily

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults with stage II or III non-small cell lung cancer who've had prior treatments like surgery, chemo, or radiation but not within the last year. They must have proper liver and kidney function, no severe active infections, HIV under control, and can't be pregnant. People with certain blood counts and those who haven't used high-dose steroids recently can join. It's not for those with autoimmune diseases needing treatment in the past 6 months or a history of significant lung disease.

Inclusion Criteria

Your AST and ALT liver enzyme levels are not more than 2.5 times the upper limit of normal.

Your disease must be able to be treated within the radiation limits set by a local radiation doctor.

Participants must not be candidates for concurrent chemoradiation in the opinion of the treating investigator

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Patients undergo hypofractionated radiation therapy 5 days per week over 3 weeks for 15 fractions

3 weeks

15 visits (in-person)

Consolidation

Patients receive atezolizumab intravenously on day 1 of each cycle, with cycles repeating every 21 days for up to 12 months

12 months

17 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Follow-up at 6 weeks, every 12 months for 1 year, then every 6 months until 3 years

Treatment Details

Interventions

• Atezolizumab
• Hypofractionated Radiation Therapy

Trial Overview The study tests if giving smaller doses of radiation over time (hypofractionated radiation therapy) before atezolizumab—an immune system-boosting drug—can effectively treat non-small cell lung cancer with fewer side effects than standard treatments.

Participant Groups

Group I: Treatment (hypofractionated radiation therapy, atezolizumab) Experimental Treatment 5 Interventions

RADIATION THERAPY: Patients undergo hypofractionated radiation therapy 5 days per week over 3 weeks for 15 fractions in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 12 months (maximum of 17 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and may undergo MRI throughout the study, as well as blood sample collection on study.

Hypofractionated Radiation Therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Approved in European Union as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Approved in Canada as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Hypofractionated radiotherapy (HFRT) for early stage non-small-cell lung cancer (NSCLC) in 26 medically inoperable patients showed a 53.9% overall response rate and a median survival duration of 27.8 months, indicating its efficacy as a treatment option.

The study found that a biologically equivalent dose (BED) greater than 90 Gy was a significant prognostic factor for better progression-free survival and local control, while severe toxicities were not observed, suggesting HFRT is a safe alternative for patients who cannot undergo surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated three-dimensional conformal radiotherapy for medically inoperable early stage non-small-cell lung cancer. Lee, JH., Wu, HG., Kim, HJ., et al.[2021]

Hypofractionated radiation therapy (HypoRT) was found to be effective in treating inoperable advanced non-small cell lung cancer (NSCLC), with an overall response rate of 83% among 30 patients, and a median follow-up of 13 months.

The treatment was well-tolerated, with manageable acute toxicities; however, 37% of patients experienced locoregional recurrence, and 57% developed distant metastasis, indicating the need for further studies to compare HypoRT with conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer. Osti, MF., Agolli, L., Valeriani, M., et al.[2018]

In a phase I study involving 31 patients with advanced lung cancer, the combination of hypofractionated radiotherapy (HFRT) and nivolumab was found to be well tolerated, with no patients developing severe pneumonitis (grade ≥ 3) during a median follow-up of 11 months.

The treatment resulted in an overall objective response rate of 39.13% and a complete remission rate of 13.04%, suggesting that HFRT may enhance the effectiveness of nivolumab and reduce the frequency of its administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and Hypofractionated Radiotherapy in Patients With Advanced Lung Cancer: ABSCOPAL-1 Clinical Trial. Ye, H., Pang, H., Shi, X., et al.[2022]

The FORCE study is a phase II trial involving 130 patients with stage IV non-squamous non-small cell lung cancer, investigating the effects of nivolumab combined with hypofractionated palliative radiotherapy, aiming to assess its safety and efficacy in improving response rates and survival outcomes.

Preliminary data suggest that combining nivolumab with radiation therapy may enhance immune responses against tumors, potentially leading to better treatment outcomes compared to nivolumab alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial. Bozorgmehr, F., Hommertgen, A., Krisam, J., et al.[2020]

In a study of 34 patients with inoperable early-stage non-small-cell lung cancer (NSCLC), three-dimensional hypofractionated radiotherapy (HFRT) demonstrated an impressive local control rate of 80.4% and regional control rate of 78% at 2 years, indicating its efficacy in managing this type of cancer.

Importantly, no severe toxicities (grade ≥3) were observed during treatment, suggesting that HFRT is a safe option for patients who cannot undergo surgery, with a recommended total dose of 66 Gy delivered in 3.0-Gy fractions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated 3D radiotherapy for inoperable T1-3 N0-1 non-small-cell lung cancer. Mollà, M., Saez, J., Ramos, M., et al.[2019]

Hypofractionated radiation therapy (HFRT) demonstrated a freedom from local progression (FFLP) rate of 79.8% at 1 year and 67.8% at 2 years in 64 patients with non-small cell lung cancer who were unfit for surgery or stereotactic body radiation therapy, indicating its efficacy in this patient population.

The treatment showed acceptable safety, with only 6.3% of patients experiencing severe pulmonary toxicities, suggesting that HFRT can be a viable option for patients who cannot undergo more aggressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of 10-fraction hypofractionated radiation therapy for non-small cell lung cancer. Yoo, YJ., Kim, SS., Song, SY., et al.[2021]

In a phase II study involving 111 high-risk prostate cancer patients, hypofractionated radiation therapy (HFRT) was found to be well tolerated, with no significant difference in acute gastrointestinal (GI) or genitourinary (GU) toxicity compared to conventionally fractionated radiation therapy (CFRT).

Both HFRT and CFRT resulted in similar 3-year biochemical recurrence-free survival rates (97.3% for HFRT vs 91.0% for CFRT) and overall survival rates (94.8% for HFRT vs 100.0% for CFRT), indicating that HFRT is a safe and effective treatment option for high-risk prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of the CHIRP Trial: A Phase II Prospective Randomized Trial of Conventionally Fractionated Versus Moderately Hypofractionated Prostate and Pelvic Nodal Radiation Therapy in Patients With High-Risk Prostate Cancer. Wang, MH., Vos, LJ., Yee, D., et al.[2021]

Combining metastasis-directed hypofractionated radiation therapy (RT) with systemic therapies can be effective, but specific timing adjustments are necessary to minimize toxicity; for example, BRAF and MEK inhibitors should be suspended a few days before and after RT due to reported toxicities.

Certain therapies like cetuximab and osimertinib are generally safe with RT, but recommendations include suspending them during radiation treatment to reduce potential side effects, highlighting the need for careful management when integrating these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Metastasis-Directed Radiation Therapy in the Era of Evolving Systemic, Immune, and Targeted Therapies. Guimond, E., Tsai, CJ., Hosni, A., et al.[2022]

In a study of 2159 patients with stage I non-small cell lung cancer, hypofractionated radiotherapy (HFRT) showed a longer overall survival (OS) compared to conventionally fractionated radiotherapy (CFRT) in univariable analysis, but this benefit was not confirmed in multivariable analysis, suggesting that the difference may not be clinically significant.

High-dose HFRT (HD-HFRT) demonstrated a statistically significant improvement in OS compared to CFRT in multivariable analysis, but this finding was not consistent across all sensitivity analyses, indicating that while HD-HFRT may be beneficial, further research is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization and Survival Impact of Hypofractionated Radiotherapy in Stage I Non-small Cell Lung Cancer. Saeed, NA., Jin, L., Amini, A., et al.[2023]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Hypofractionated three-dimensional conformal radiotherapy for medically inoperable early stage non-small-cell lung cancer. [2021]

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

Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Nivolumab and Hypofractionated Radiotherapy in Patients With Advanced Lung Cancer: ABSCOPAL-1 Clinical Trial. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Hypofractionated 3D radiotherapy for inoperable T1-3 N0-1 non-small-cell lung cancer. [2019]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety and efficacy of 10-fraction hypofractionated radiation therapy for non-small cell lung cancer. [2021]

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

Clinical Outcomes of the CHIRP Trial: A Phase II Prospective Randomized Trial of Conventionally Fractionated Versus Moderately Hypofractionated Prostate and Pelvic Nodal Radiation Therapy in Patients With High-Risk Prostate Cancer. [2021]

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

Safety and Tolerability of Metastasis-Directed Radiation Therapy in the Era of Evolving Systemic, Immune, and Targeted Therapies. [2022]

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

Utilization and Survival Impact of Hypofractionated Radiotherapy in Stage I Non-small Cell Lung Cancer. [2023]