SBRT +/− Nivolumab for Lung Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining precise radiation therapy with the medication nivolumab for treating non-small cell lung cancer that is either early-stage or recurrent. The radiation therapy targets tumors with high accuracy, while nivolumab, an immunotherapy drug, helps the immune system fight cancer cells. The trial will compare the effects of radiation alone to those of radiation combined with nivolumab. Individuals with non-small cell lung cancer that is less than 7 cm in size, has not spread to other parts of the body, and who have not received similar treatments before may be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants, offering a chance to contribute to significant advancements in cancer therapy.

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.

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

Research has shown that nivolumab, a treatment that aids the immune system in fighting cancer, is usually well-tolerated by individuals with non-small cell lung cancer. Common side effects include fatigue, muscle aches, coughing, and shortness of breath. These side effects occurred in more than 20% of patients in past studies but were generally manageable.

For stereotactic body radiation therapy (SBRT), research indicates it can be safely used to treat lung cancer. Most patients handle this treatment well, though there is a small risk of serious lung inflammation.

Both treatments have demonstrated safety in previous studies. Participants in a trial using these treatments might experience some side effects, but serious issues are rare. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of stereotactic body radiation therapy (SBRT) and nivolumab for lung cancer because it offers a potentially powerful one-two punch against tumors. Unlike traditional chemotherapy, which attacks cancer cells broadly, SBRT delivers precise, high doses of radiation directly to the tumor over a short period, minimizing damage to surrounding healthy tissue. Nivolumab, on the other hand, is an immunotherapy drug that helps the immune system recognize and attack cancer cells more effectively. This combination could enhance the immune response while precisely targeting the cancer, offering hope for improved outcomes with potentially fewer side effects.

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

This trial will compare the effectiveness of stereotactic body radiation therapy (SBRT) alone and in combination with nivolumab for lung cancer. Research has shown that nivolumab works well for non-small cell lung cancer (NSCLC). In studies, nivolumab helped some patients live more than a year longer after treatment. SBRT effectively targets tumors in early-stage lung cancer, minimizing harm to healthy tissue. Combining SBRT with nivolumab might enhance the immune system's ability to fight cancer and improve outcomes. Together, these treatments offer hope for better control of lung cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Joe Y Chang, MD,MS,PHD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

Citations

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Efficacy Data for Non-Small Cell Lung Cancer (NSCLC) - Opdivo Fatal adverse reactions occurred in 3.6% of patients who received OPDIVO in combination with chemotherapy; these included sepsis (1%). OPDIVO and/or ...

2. opdivo.com opdivo.com/nsclc/clinical-trial-results/advanced-previously-treated-immunotherapy

Clinical trial results for previously treated stage 4 recurrent ... 42% of patients given OPDIVO® (nivolumab) for advanced squamous NSCLC were alive. People ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4346216/

Nivolumab in NSCLC: latest evidence and clinical potential Updated results presented in abstract form reported prolonged survival with a median of 9.2–14.9 months across the cohorts with a 1-year survival of 32–56% and ...

4. nejm.org nejm.org/doi/pdf/10.1056/NEJMoa2502931

Overall Survival with Neoadjuvant Nivolumab plus ... Neoadjuvant nivolumab plus chemotherapy significantly improved pathological com- plete response and event-free survival in patients with ...

5. jto.org jto.org/article/S1556-0864(24)02355-4/fulltext

Long-Term Survival Outcomes With First-Line Nivolumab ... In patients with squamous NSCLC, median OS was 16.2 versus 8.2 months with nivolumab plus ipilimumab with or without chemotherapy versus ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8586674/

Real‐world safety of nivolumab in patients with non‐small‐ ... The 12‐month survival rate was 40.7%. In conclusion, the safety profile of nivolumab in this postmarketing surveillance was similar to that in clinical trials, ...

7. opdivohcp.com opdivohcp.com/efficacy/nsclc/opdivo

5 years of OS data in 2L mNSCLC 1,2 - Opdivo In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and ...

8. opdivo.com opdivo.com/clinical-trial-results

Clinical Trial Results Access OPDIVO® clinical trial results for your cancer type. Please see Indication and Important Safety Information ... lung cancer (called non-small cell lung ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01503

Five-Year Survival Outcomes With Nivolumab Plus ... Patients with metastatic non–small-cell lung cancer (mNSCLC) have historically had a 5-year survival rate of only 7%, but more recently, immune ...