Radiation + Immunotherapy for Non-Small Cell Lung Cancer

Recruiting at 175 trial locations

Overseen By Megan E. Daly

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: National Cancer Institute (NCI)

Must be taking: Immunotherapy

Must not be taking: Tyrosine inhibitors, Steroids

Disqualifiers: Auto-immune disease, Pneumonitis, Hepatitis, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase II/III trial compares the addition of radiation therapy to the usual treatment (immunotherapy with or without chemotherapy) versus (vs.) usual treatment alone in treating patients with non-small cell lung cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic) whose tumor is also negative for a molecular marker called PD-L1. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The addition of radiation therapy to usual treatment may stop the cancer from growing and increase the life of patients with advanced non-small cell lung cancer who are PD-L1 negative.

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, you cannot take systemic immunostimulatory or immunosuppressive drugs, including more than 10 mg of prednisone per day, within two weeks before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of this treatment for non-small cell lung cancer?

Research shows that combining nanoparticle albumin-bound paclitaxel with carboplatin and radiation therapy is effective and well-tolerated in patients with advanced non-small cell lung cancer. Additionally, using these drugs in combination has shown favorable results, especially in elderly patients, with less nerve-related side effects. ^{1 2 3 4 5}

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

Research shows that treatments involving nanoparticle albumin-bound paclitaxel (nab-paclitaxel) combined with other drugs like carboplatin and radiation have been studied for safety in non-small cell lung cancer. These studies aim to find the safest doses and have generally shown that these combinations can be used safely, although side effects may occur. ^{1 2 5 6 7}

What makes the Radiation + Immunotherapy treatment for non-small cell lung cancer unique?

This treatment is unique because it combines radiation with a mix of chemotherapy drugs and immunotherapy, which may enhance the body's immune response against cancer cells. The combination of drugs like carboplatin, nab-paclitaxel, and immunotherapy agents like nivolumab and pembrolizumab aims to improve treatment effectiveness by targeting cancer cells in multiple ways. ^{2 3 5 8 9}

Research Team

Christine M Bestvina

Principal Investigator

Alliance for Clinical Trials in Oncology

Eligibility Criteria

Adults with advanced non-small cell lung cancer that's spread and is PD-L1 negative can join. They shouldn't have had chemotherapy or immunotherapy for metastatic NSCLC, no recent pneumonitis, no active infections or serious heart conditions, and must not be pregnant. Prior therapy for non-metastatic disease is okay if it ended over 6 months ago.

Inclusion Criteria

I am able to care for myself and perform daily activities.

I haven't taken strong immune system drugs or more than 10 mg of steroids daily in the last 2 weeks.

I don't have any serious illnesses that would stop me from following the study's requirements.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive nivolumab and ipilimumab intravenously every 6 weeks for up to 24 months, with or without radiation therapy

24 months

Every 6 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Every 3 months for 3 years, then every 6 months for 2 years (in-person)

Treatment Details

Interventions

• Carboplatin (Platinum-containing Compound)
• Nab-paclitaxel (Chemotherapy)
• Nivolumab (Checkpoint Inhibitor)
• Paclitaxel (Chemotherapy)
• Pembrolizumab (Checkpoint Inhibitor)
• Pemetrexed (Chemotherapy)
• Stereotactic Body Radiation Therapy (Radiation)

Trial Overview The trial tests adding radiation to usual treatments (immunotherapy with/without chemo) in stage IV lung cancer patients who are PD-L1 negative. It compares the effects of this combination against usual treatment alone on tumor growth and patient survival.

Participant Groups

Group I: Arm B (immunotherapy, +/- chemotherapy, radiation therapy) Experimental Treatment 10 Interventions

Patients receive 1 of 6 treatment options as in Arm A. Patients also undergo 3 fractions of radiation therapy every other day. Patients also undergo MRI, CT, or PET throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as ECHO during screening.

Group II: Arm A (immunotherapy, +/- chemotherapy) Experimental Treatment 9 Interventions

Patients receive nivolumab intravenously (IV) over 30 minutes on days 1 and 22 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity or patients may receive standard of care systemic immunotherapy. Patients also undergo MRI, CT, or PET throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as ECHO during screening.

Carboplatin is already approved in Canada for the following indications:

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

The combination of pemetrexed and nab-paclitaxel was found to be feasible and well tolerated in patients with advanced non-small cell lung cancer (NSCLC), with a recommended phase II dose established at pemetrexed 500 mg/m² and nab-paclitaxel 260 mg/m².

In a phase II trial involving 37 patients, the treatment showed a response rate of 14% and a disease control rate of 46%, with a median overall survival of 8.8 months, indicating some efficacy in second and third-line therapy despite the early closure of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of pemetrexed plus nab-paclitaxel in advanced solid tumor patients with emphasis on non-small cell lung cancer. Ho, C., Davies, AM., Sangha, RS., et al.[2023]

The maximum tolerated dose (MTD) and recommended dose (RD) of nab-paclitaxel plus carboplatin, combined with thoracic radiotherapy, was determined to be at level 3 (80 mg/m2 of nab-paclitaxel and 2 mg/ml/min of carboplatin), with no significant pulmonary toxicities observed.

The treatment regimen was well tolerated, with 71.4% of patients showing an objective response, indicating its potential efficacy for patients with locally advanced non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of nab-paclitaxel plus carboplatin and concurrent thoracic radiotherapy in patients with locally advanced non-small cell lung cancer. Kaira, K., Tomizawa, Y., Imai, H., et al.[2017]

In a study of 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

In a phase II trial involving 32 elderly patients with untreated advanced non-small cell lung cancer, the combination of weekly nanoparticle albumin-bound-paclitaxel and carboplatin showed a 50% overall response rate and a median overall survival of 17.5 months, indicating significant efficacy.

The treatment was well tolerated, with no treatment-related deaths or febrile neutropenia reported, and it resulted in less neuropathic toxicity compared to traditional regimens, making it a promising option for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Modified Carboplatin Plus Weekly Nab-Paclitaxel in Elderly Patients with Non-Small Cell Lung Cancer: North Japan Lung Cancer Study Group Trial 1301. Miyauchi, E., Inoue, A., Usui, K., et al.[2018]

In a Phase 2 study involving 29 patients with advanced non-small cell lung cancer (NSCLC) who had previously failed PD-(L)1 inhibitor treatment, nab-paclitaxel demonstrated a promising objective response rate (ORR) of 55.2%, indicating its efficacy as a subsequent treatment option.

The treatment was associated with manageable safety profiles, with significant toxicities including leukopenia (27.6%) and neutropenia (31.0%), suggesting that while nab-paclitaxel is effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non-small cell lung cancer: A multicenter Phase 2 clinical trial. Sonoda, T., Umeda, Y., Demura, Y., et al.[2023]

In a phase III trial involving 1,052 patients with advanced non-small-cell lung cancer, nab-paclitaxel plus carboplatin showed a significantly higher overall response rate (33%) compared to solvent-based paclitaxel plus carboplatin (25%), indicating greater efficacy in treatment.

Nab-paclitaxel was associated with fewer severe side effects, such as neuropathy and neutropenia, compared to solvent-based paclitaxel, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. Socinski, MA., Bondarenko, I., Karaseva, NA., et al.[2022]

In a study of 40 patients with stage III/IV squamous non-small-cell lung cancer, the combination of nab-paclitaxel and a platinum agent (cisplatin or carboplatin) resulted in a high overall response rate of 62.5% and a disease control rate of 92.5%, indicating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with most adverse effects being mild to moderate (grade 1 to 2), including myelosuppression and gastrointestinal issues, suggesting that nab-paclitaxel combined with platinum agents is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. Fang, Y., Wang, L., Xia, GH., et al.[2022]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

In a study involving 180 patients with advanced non-small cell lung cancer (NSCLC), pemetrexed-carboplatin did not show superior efficacy compared to paclitaxel-carboplatin, with similar progression-free survival (PFS) rates and overall survival after a median follow-up of 17 months.

While both treatment regimens had comparable overall toxicities, the paclitaxel-carboplatin group experienced higher rates of alopecia and peripheral neuropathy, indicating a difference in side effects between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Open-Label Randomized Controlled Trial Comparing the Efficacy and Safety of Pemetrexed-Carboplatin versus (Weekly) Paclitaxel-Carboplatin as First-Line Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer. Yadav, A., Malik, PS., Khurana, S., et al.[2021]

References

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

Phase I/II trial of pemetrexed plus nab-paclitaxel in advanced solid tumor patients with emphasis on non-small cell lung cancer. [2023]

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

Phase I study of nab-paclitaxel plus carboplatin and concurrent thoracic radiotherapy in patients with locally advanced non-small cell lung cancer. [2017]

3. China pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. [2010]

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

Phase II Study of Modified Carboplatin Plus Weekly Nab-Paclitaxel in Elderly Patients with Non-Small Cell Lung Cancer: North Japan Lung Cancer Study Group Trial 1301. [2018]

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

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non-small cell lung cancer: A multicenter Phase 2 clinical trial. [2023]

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

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. [2022]

7. Thailand pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. [2022]

8. China pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

An Open-Label Randomized Controlled Trial Comparing the Efficacy and Safety of Pemetrexed-Carboplatin versus (Weekly) Paclitaxel-Carboplatin as First-Line Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer. [2021]