Chemoimmunotherapy + Radiation for Lung Cancer

(NEORADJUVANT Trial)

Recruiting at 3 trial locations

Overseen By Caitlin Eggleston, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Maryland, Baltimore

Must not be taking: Corticosteroids, Immunosuppressants, Anti-PD-(L)1

Disqualifiers: Metastatic disease, Brain metastases, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding radiation before chemoimmunotherapy and surgery effectively treats non-small cell lung cancer (NSCLC) that can potentially be removed surgically. Participants will receive standard chemotherapy drugs combined with the immunotherapy drug nivolumab, along with targeted radiation therapy. The trial seeks individuals with stage II-IIIC NSCLC that might be surgically removed and who do not have widespread cancer. This study could help determine if this approach improves patient outcomes and reduces cancer recurrence.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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 enrolling in the study.

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

Research has shown that combining nivolumab with stereotactic body radiation therapy (SBRT) and chemotherapy is generally safe. One study found that serious side effects from nivolumab alone occurred in 10% to 18% of participants. For radiation treatments alone, serious side effects ranged from 0% to 26%. Another study suggested that using SBRT with drugs like nivolumab can be safe if doctors carefully protect healthy tissues. However, there is a risk of lung inflammation, so patients require close monitoring. Overall, this combination treatment is considered reasonably safe, but vigilance for side effects remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining chemoimmunotherapy with radiation for lung cancer because it offers a novel approach that could enhance outcomes. Unlike traditional treatments that focus solely on chemotherapy or radiation, this combination uses nivolumab, an immunotherapy drug that helps the immune system recognize and attack cancer cells. Additionally, the use of SBRT (stereotactic body radiation therapy) allows for more targeted radiation, potentially reducing side effects and improving precision. This integrated approach could lead to more effective cancer control and possibly enable surgical options for patients who might not have been candidates before.

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

Research has shown that stereotactic body radiation therapy (SBRT), when combined with chemoimmunotherapy, can extend the lives of people with non-small cell lung cancer (NSCLC). In this trial, participants will receive SBRT alongside nivolumab, a drug that enhances the immune system, and standard chemotherapy. Studies have found SBRT to be more effective than traditional radiation methods. This combination can potentially increase overall survival time, with patients in these studies living a median of up to 44 months. This approach not only directly targets cancer cells but also enhances the immune system's ability to combat the cancer. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for individuals with borderline resectable non-small cell lung cancer (NSCLC) who may be candidates for surgery. Participants should not have had prior treatments for NSCLC and must be able to undergo chemotherapy, immunotherapy with nivolumab, and stereotactic body radiation therapy (SBRT).

Inclusion Criteria

I don't have any major health issues that make surgery too risky.

I have confirmed I am not pregnant through a test in the last 30 days.

My case has been reviewed by a team of lung cancer experts.

Exclusion Criteria

I do not have an active autoimmune disease that prevents immunotherapy.

I am allergic to nivolumab or certain chemotherapy drugs.

History of allogeneic organ transplantation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive three doses of stereotactic body radiation therapy (SBRT) delivered every other day over three days

1 week

Chemoimmunotherapy

Participants receive standard of care chemotherapy and the immunotherapy drug nivolumab intravenously every 3 weeks for up to 3 cycles

9 weeks

Follow-up

Participants are monitored for potential side effects for up to 100 days following the last chemoimmunotherapy dose

14 weeks

Long-term follow-up

Participants continue with standard follow-up with their doctor, and study staff review charts for updates on cancer status

1 year post completion of accrual

What Are the Treatments Tested in This Trial?

Interventions

• Chemotherapy
• Nivolumab
• SBRT

Trial Overview The study tests if adding SBRT before standard chemoimmunotherapy improves outcomes in NSCLC patients eligible for surgery. Patients receive three doses of SBRT followed by up to three cycles of chemotherapy combined with the immunotherapy drug nivolumab before a surgical assessment.

How Is the Trial Designed?

Group I: SBRT+Chemoimmunotherapy +/-Surgery Experimental Treatment 4 Interventions

Standard of care chemotherapy along with nivolumab. Nivolumab will be infused every 3 weeks for up to 3 cycles. Chemotherapy options include: carboplatin or cisplatin along with pemetrexed, paclitaxel or gemcitabine. Concurrently patient will receive 3 fractions of SBRT. Patient will then be evaluated for possible surgical resection.

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

In a feasibility study involving six patients with advanced non-small-cell lung cancer, nivolumab was administered after stereotactic radiation therapy, showing good tolerance with only one case of Grade 3 pneumonitis and no other serious adverse events.

The combination treatment resulted in one complete response and two partial responses, indicating potential effectiveness, especially in patients with lesions outside the irradiated area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and stereotactic radiation therapy for the treatment of patients with Stage IV non-small-cell lung cancer. Miyamoto, S., Nomura, R., Sato, K., et al.[2022]

Radiation therapy (RT) is crucial for controlling non-small cell lung cancer (NSCLC), but it often fails to prevent distant metastases, leading to poor patient outcomes.

Recent advancements in combining RT with immune checkpoint blockade immunotherapy show promise in enhancing systemic anti-tumor responses in NSCLC, similar to successful strategies seen in melanoma, with ongoing clinical trials exploring this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experiences of combining immunotherapy and radiation therapy in non-small cell lung cancer: lessons from melanoma. Kalbasi, A., Rengan, R.[2020]

The RTOG 3505 study is investigating the effectiveness of combining concurrent chemoradiation with the immune checkpoint inhibitor nivolumab in patients with locally advanced non-small-cell lung cancer, aiming to improve overall survival and progression-free survival.

With a planned enrollment of 660 patients, the study is designed to have sufficient power to detect significant differences in survival outcomes, ensuring robust results regarding the efficacy of nivolumab compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Design and Rationale for a Randomized Trial of Cisplatin and Etoposide Plus Thoracic Radiotherapy Followed by Nivolumab or Placebo for Locally Advanced Non-Small-Cell Lung Cancer (RTOG 3505). Gerber, DE., Urbanic, JJ., Langer, C., et al.[2018]

The combination of PD-1/PD-L1 blockade with thoracic radiotherapy is now the standard treatment for locally advanced non-small-cell lung cancer, but safety data is primarily from retrospective studies and small clinical trials.

There is a need for longer and more rigorous follow-up studies to better understand the pulmonary safety and potential toxicity of this combined therapy in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rethinking pulmonary toxicity in advanced non-small cell lung cancer in the era of combining anti-PD-1/PD-L1 therapy with thoracic radiotherapy. Li, M., Gan, L., Song, A., et al.[2019]

Concurrent immunoradiotherapy, combining immune checkpoint inhibitors with radiotherapy, showed a 30% overall response rate in 16 patients with metastatic melanoma who had progressed on nivolumab, with a notable 68.8% response rate in lesions within the radiation fields.

Nivolumab combined with radiotherapy demonstrated a 100% response rate inside the radiation fields, suggesting it may be more effective than ipilimumab in this setting, although some patients experienced grade 3 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab. Nomura, M., Otsuka, A., Yoshimura, M., et al.[2019]

In a study of 60 patients receiving combined immunotherapy and thoracic radiation therapy (iRT), no patients experienced severe grade ≥4 toxicities, indicating a favorable safety profile for this treatment approach.

While some patients did experience grade 3 toxicities, particularly pulmonary and hematologic issues, the overall short-term safety of iRT suggests it can be administered without significant risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. Verma, V., Cushman, TR., Selek, U., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10511897/

Combining stereotactic body radiotherapy with ... Compared with conventionally fractionated radiation therapy (CFRT), SBRT is associated with less lymphopenia and better clinical efficacy (65–67). Therefore, ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0360301621009263

A Randomized Phase 2 Trial of Nivolumab and ... Nivolumab plus SABR demonstrated similar activity and safety to nivolumab alone in NSCLC progressing after 1 or 2 lines of chemotherapy, with a potential ...

3. redjournal.org redjournal.org/article/S0360-3016(24)00508-X/fulltext

Safety and Efficacy of Stereotactic Body Radiation Therapy ... The median PFS was 8.8 months, while the median overall survival was 44.0 months. Conclusions. In the largest case series of ultracentral ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05500092

NCT05500092 | An Open Label, Randomized Study of ... An Open Label, Randomized Study of Neoadjuvant Nivolumab and Chemotherapy, With or Without Sub-ablative Stereotactic Body Radiation Therapy, for Resectable ...

5. onclive.com onclive.com/view/sbrt-shines-in-early-stage-nsclc-and-demonstrates-efficacy-with-immunotherapy

SBRT Shines in Early-Stage NSCLC and Demonstrates ... The median overall survival (OS) was 8.7 months (IQR, 6.4-11.0) for those who received the immunotherapy alone (n = 76) compared with 19.2 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6128090/

Multi-institutional report on toxicities of concurrent nivolumab ... The rate of grade ≥3 toxicities from nivolumab monotherapy and radiation-only palliative treatments has been reported at 10% to 18% and 0% to 26%, respectively.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804924009201

Safety of combined ablative radiotherapy and immune ... We conclude that multi-site SBRT and ICI can be safely co-administered when SBRT is delivered with prioritization of normal tissue constraints.

8. redjournal.org redjournal.org/article/S0360-3016(20)32614-6/pdf

Efficacy and Safety of Stereotactic Body Radiotherapy for Non- ... Purpose/Objective(s): The purpose of this study was to assess patterns of disease progression for patients with metastatic non-small cell lung cancer.

9. aacrjournals.org aacrjournals.org/clincancerres/article/27/20/5510/671680/Phase-I-Study-of-Stereotactic-Body-Radiotherapy

Phase I Study of Stereotactic Body Radiotherapy plus ... We evaluated the safety and efficacy of SBRT with nivolumab+urelumab (CD137 agonist) or nivolumab+cabiralizumab (CSF1R inhibitor). Patients and ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7747230/

Lung Stereotactic Body Radiation Therapy and Concurrent ... Conclusions: Overall, concurrent lung SBRT + ICI is safe. Given the clinically meaningful risk of pneumonitis, closer monitoring should be considered for SBRT ...