SBRT +/− Nivolumab for Lung Cancer

Recruiting at 2 trial locations

Overseen By Joe Y Chang, MD,MS,PHD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunotherapy, Corticosteroids

Disqualifiers: Tumors > 7 cm, Metastases, Autoimmune, 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: 3

140 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may not be eligible to participate.

What data supports the effectiveness of the treatment SBRT +/− Nivolumab for Lung Cancer?

Research shows that Stereotactic Ablative Radiotherapy (SABR), especially using the CyberKnife system, is effective for treating early-stage non-small cell lung cancer (NSCLC) with high rates of tumor control and manageable side effects. While Nivolumab (an immune checkpoint inhibitor) is not specifically mentioned in these studies, it is being tested in combination with SABR in ongoing trials for its potential benefits in treating lung cancer. ^{1 2 3 4 5}

Is SBRT using CyberKnife safe for lung cancer patients?

Stereotactic Body Radiation Therapy (SBRT) using the CyberKnife system has been shown to be generally safe for treating early-stage non-small cell lung cancer, with studies reporting acceptable levels of side effects and good tumor control. ^{1 2 3 6 7}

How is the treatment SBRT +/− Nivolumab for lung cancer different from other treatments?

This treatment combines Stereotactic Body Radiation Therapy (SBRT), which precisely targets lung tumors with high doses of radiation, with Nivolumab, an immunotherapy drug that helps the immune system attack cancer cells. This combination is unique because it leverages both precise radiation and immune system activation, potentially offering better control of lung cancer compared to traditional treatments. ^{1 2 8 9 10}

What is the purpose of this trial?

This phase II trial studies how well stereotactic body radiation therapy with or without nivolumab works in treating patients with stage I-IIA non-small cell lung cancer or cancer that has come back. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving stereotactic body radiation therapy and nivolumab may work better at treating non-small cell lung cancer.

Research Team

Joe Y Chang, MD,MS,PHD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with stage I-IIA or recurrent non-small cell lung cancer without distant metastases. Participants must have completed any prior treatments at least 12 weeks before, tumors should be ≤7 cm (N0M0), and they should use effective birth control. They need to meet certain blood count criteria, have a performance status score of 0-2, and sign consent forms.

Inclusion Criteria

All patients of childbearing potential should use effective birth control throughout their participation in this study

My lung cancer came back in the same place after surgery or chemo/radiotherapy.

I have early-stage lung cancer and cannot undergo surgery due to other health issues.

Exclusion Criteria

Patients with allergies or adverse drug reactions to specific components are not eligible

My tumor is not larger than 7 cm and does not involve critical body parts.

I am not planning to receive other treatments while on this trial, except if my disease worsens.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Patients undergo stereotactic body radiation therapy over 1-2 weeks

1-2 weeks

Immunotherapy

Patients receive nivolumab intravenously every 4 weeks for up to 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

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

Treatment Details

Interventions

• Nivolumab
• Stereotactic Body Radiation Therapy

Trial Overview The trial is testing the effectiveness of stereotactic body radiation therapy (SBRT) alone versus SBRT combined with Nivolumab, an immunotherapy drug. SBRT targets tumors precisely to minimize damage to healthy tissue while Nivolumab aims to boost the immune system's response against cancer cells.

Participant Groups

Group I: Arm II (stereotactic body radiation therapy, nivolumab) Experimental Treatment 2 Interventions

Patients undergo stereotactic body radiation therapy over 1-2 weeks. Beginning within 36 hours before or after the first fraction of stereotactic body radiation therapy, patients also receive nivolumab IV over 30 minutes on day 1. Cycles with nivolumab repeat every 4 weeks for up to 12 weeks in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (stereotactic body radiation therapy) Experimental Treatment 1 Intervention

Patients undergo stereotactic body radiation therapy over 1-2 weeks.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In a study of 100 patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative body radiotherapy (SABR), the 1-, 2-, and 3-year local control rates were 100%, 93.55%, and 84.33%, respectively, indicating high efficacy in tumor control.

The treatment was associated with low toxicity, with only 2% of patients experiencing Grade-3 side effects, suggesting that SABR is a safe option for patients who are inoperable or refuse surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definitive Treatment of Early-Stage Non-Small Cell Lung Cancer with Stereotactic Ablative Body Radiotherapy in a Community Cancer Center Setting. Heal, C., Ding, W., Lamond, J., et al.[2020]

Stereotactic ablative radiotherapy (SABR) is an effective treatment for early-stage non-small cell lung cancer, especially for patients who cannot undergo surgery, showing high local tumor control rates with manageable side effects.

The CyberKnife system is particularly advantageous for SABR in lung tumors due to its ability to accurately target moving tumors during breathing, enhancing treatment precision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CyberKnife stereotactic ablative radiotherapy for lung tumors. Gibbs, IC., Loo, BW.[2022]

Stereotactic ablative radiotherapy (SABR) using Cyberknife demonstrated high effectiveness in treating stage I non-small-cell lung cancer, with 2-year local control, progression-free, and overall survival rates of 91.9%, 61.7%, and 84.8%, respectively, based on a study of 153 patients.

The treatment was generally safe, with only 8.1% of patients experiencing severe toxicities, including one case of grade 5 radiation pneumonitis, indicating that while SABR is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. Hayashi, K., Suzuki, O., Shiomi, H., et al.[2022]

Stereotactic ablative radiotherapy (SABR) is the standard treatment for early-stage non-small-cell lung cancer that cannot be surgically removed, showing high rates of tumor control but facing challenges with regional and distant tumor failures.

Current research is exploring the use of immune checkpoint inhibitors as a systemic therapy option for patients treated with SABR, aiming to provide effective treatment with fewer side effects compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inoperable Early-Stage Non-Small-Cell Lung Cancer: Stereotactic Ablative Radiotherapy and Rationale for Systemic Therapy. Daly, ME.[2022]

In a study of 106 patients with early-stage non-small cell lung cancer treated with CyberKnife® SBRT, the treatment demonstrated an 88% local control rate at 2 years, indicating its efficacy in managing this type of cancer.

The treatment was associated with low toxicity, with only 20% of patients experiencing mild fatigue and 17% mild dyspnea, and only 4% experiencing significant late effects, suggesting it is a safe option for medically inoperable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer. Temming, S., Kocher, M., Stoelben, E., et al.[2022]

A collaborative program for implementing stereotactic ablative radiotherapy (SABR) for non-small cell lung cancer (NSCLC) across multiple centers in New South Wales has been successfully established, demonstrating a safe and efficient approach to treatment.

In a study involving 41 patients, the early toxicity profile of SABR was consistent with existing literature, and there was no significant impact on quality of life, indicating that SABR can be a viable treatment option for lung cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Collaborative implementation of stereotactic ablative body radiotherapy: A model for the safe implementation of complex radiotherapy techniques in Australia. Hau, E., Hegi-Johnson, F., Atkinson, C., et al.[2020]

In a phase 1 trial involving 37 treatment-naive patients with stage IV NSCLC, combining concurrent stereotactic body radiotherapy (SBRT) with nivolumab and ipilimumab showed no dose-limiting toxicities, indicating a favorable safety profile for this multimodal treatment approach.

The study reported a median progression-free survival of 5.8 months and demonstrated that concurrent therapy was well tolerated, suggesting that this combination could effectively control metastasis in widely metastatic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 Trial of Concurrent or Sequential Ipilimumab, Nivolumab, and Stereotactic Body Radiotherapy in Patients With Stage IV NSCLC Study. Bestvina, CM., Pointer, KB., Karrison, T., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Definitive Treatment of Early-Stage Non-Small Cell Lung Cancer with Stereotactic Ablative Body Radiotherapy in a Community Cancer Center Setting. [2020]

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

CyberKnife stereotactic ablative radiotherapy for lung tumors. [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Stereotactic radiotherapy (SABR) for the treatment of primary non-small cell lung cancer; systematic review and comparison with a surgical cohort. [2022]

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

Inoperable Early-Stage Non-Small-Cell Lung Cancer: Stereotactic Ablative Radiotherapy and Rationale for Systemic Therapy. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy for lung cancer. [2018]

8. Australia pubmed.ncbi.nlm.nih.gov

Collaborative implementation of stereotactic ablative body radiotherapy: A model for the safe implementation of complex radiotherapy techniques in Australia. [2020]

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

A Phase 1 Trial of Concurrent or Sequential Ipilimumab, Nivolumab, and Stereotactic Body Radiotherapy in Patients With Stage IV NSCLC Study. [2022]

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

Survey of the Patterns of Using Stereotactic Ablative Radiotherapy for Early-Stage Non-small Cell Lung Cancer in Korea. [2018]