High-Dose Radiation + Chemotherapy and Immunotherapy for Non-Small Cell Lung Cancer

Recruiting at 498 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: NRG Oncology

Disqualifiers: Prior radiotherapy, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Up to 1 year

474 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding a precise type of radiation therapy, called stereotactic body radiation therapy (SBRT), to the usual treatment plan can more effectively treat non-small cell lung cancer that has spread nearby and cannot be removed by surgery. The usual treatment includes chemotherapy, which kills cancer cells, and immunotherapy, which boosts the immune system to fight cancer. The goal is to determine if SBRT can target tumors more accurately, possibly reducing damage to healthy tissue and shortening treatment time. People with non-small cell lung cancer that has spread to nearby tissue or lymph nodes, who cannot undergo surgery, might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss your specific situation with the trial coordinators or your doctor.

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

Research shows that stereotactic body radiation therapy (SBRT) is usually well-tolerated. Studies have found that SBRT effectively controls lung tumors with side effects that most patients find acceptable, whether they have early-stage or advanced lung cancer. While some risk of side effects exists, most patients handle the treatment without major problems.

Research also supports the safety of image-guided radiation therapy (IGRT). It targets tumors more precisely, making the treatment more accurate and potentially reducing side effects compared to other methods.

Chemotherapy drugs like carboplatin, cisplatin, and paclitaxel are well-known and widely used. These drugs can cause side effects like nausea, tiredness, and low blood counts, but these are generally manageable. Many patients tolerate these drugs well, especially with supportive care.

Studies have shown that immunotherapy with durvalumab can be effective with manageable side effects. Common side effects include tiredness and cough, but serious reactions are less common.

Osimertinib, used as a targeted therapy, is known for treating certain types of lung cancer. It usually causes fewer severe side effects compared to some traditional chemotherapies. Common issues may include diarrhea and skin rash.

Overall, previous studies have shown that the treatments in this trial are generally safe, with side effects that are often manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment approach for non-small cell lung cancer because it combines high-dose radiation with both chemotherapy and a cutting-edge immunotherapy drug called durvalumab. Unlike standard treatments that primarily rely on chemotherapy and radiation, this regimen leverages the power of the immune system to fight cancer more effectively. Durvalumab is an immune checkpoint inhibitor, which means it helps the immune system recognize and attack cancer cells. Additionally, the use of image-guided radiation therapy (IGRT) and stereotactic body radiation therapy (SBRT) allows for more precise targeting of tumors, potentially reducing damage to surrounding healthy tissue. This combination of therapies aims to improve outcomes by both directly attacking cancer cells and enhancing the body's natural defenses against the disease.

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

This trial will compare two treatment approaches for non-small cell lung cancer (NSCLC). In one arm, participants will receive image-guided radiation therapy (IGRT) combined with chemotherapy and immunotherapy. In the other arm, participants will receive stereotactic body radiation therapy (SBRT) in addition to IGRT, along with chemotherapy and immunotherapy.

Research has shown that adding SBRT to treatment can be promising for NSCLC. SBRT, a precise form of radiation, targets tumors effectively, often with fewer side effects. Studies have found that this method works well, especially in early-stage NSCLC, improving outcomes for patients who cannot undergo surgery.

Regarding chemotherapy and immunotherapy, drugs like cisplatin and carboplatin are known to stop or slow cancer growth. Durvalumab, an immunotherapy, helps the immune system fight cancer. Osimertinib targets a protein that aids cancer cell growth, slowing their spread. Together, these treatments have proven effective in many cases of NSCLC. ^{6 7 8 9 10}

Who Is on the Research Team?

Charles B Simone

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

Adults aged 18+ with stage II or III non-small cell lung cancer (NSCLC) that can't be surgically removed, but haven't had extensive prior treatment. They must have a performance status indicating they're still fairly active and able to care for themselves. Participants need functioning organs, no serious concurrent illnesses, and if of childbearing potential, agree to use contraception.

Inclusion Criteria

My cancer has spread to at least one lymph node.

Your kidneys should be working well enough to filter at least 25 milliliters of waste from your blood every minute.

My doctors believe a combined treatment could potentially cure my cancer.

Exclusion Criteria

I am not pregnant and not nursing.

I do not have cancer that started in an unknown place with a swollen lymph node.

I am willing to use effective birth control during and after my treatment as required.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive stereotactic body radiation therapy (SBRT) or conventional image guided radiation therapy (IGRT) with concurrent chemotherapy, followed by consolidation immunotherapy with durvalumab or osimertinib.

Up to 1 year

Weekly visits during radiotherapy, bi-weekly or monthly visits during immunotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, including CT and/or PET/CT scans.

8 years

Every 3 months for 1 year, every 6 months for years 2 and 3, then yearly

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Durvalumab
• Etoposide
• Image Guided Radiation Therapy
• Paclitaxel
• Pemetrexed
• Stereotactic Body Radiation Therapy

Trial Overview The trial is testing whether adding high-dose targeted radiation (SBRT) to the usual combination of image-guided radiation therapy (IGRT), chemotherapy drugs like cisplatin or carboplatin with paclitaxel, pemetrexed or etoposide, followed by immunotherapy drug durvalumab improves outcomes in inoperable NSCLC compared to standard treatment alone.

How Is the Trial Designed?

Group I: Arm II (SBRT, image guided RT, chemotherapy, immunotherapy) Experimental Treatment 13 Interventions

Patients undergo SBRT and conventional IGRT and then receive standard-of-care chemotherapy consisting of paclitaxel IV followed by carboplatin IV Q7D during radiotherapy or pemetrexed IV followed by carboplatin IV every 21 days during radiotherapy or etoposide IV on days 1 to 5 and days 29 to 33 followed by cisplatin IV on days 1, 8, 29, and 36 or pemetrexed IV followed by cisplatin IV every 21 days during radiotherapy. Patients then receive consolidation durvalumab IV every 2 or 4 weeks for up to one year or osimertinib PO QD in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT during follow-up.

Group II: Arm I (image guided RT, chemotherapy, immunotherapy) Active Control 12 Interventions

Patients undergo conventional IGRT and receive usual care chemotherapy consisting of paclitaxel IV followed by carboplatin IV Q7D during radiotherapy or pemetrexed IV followed by carboplatin IV every 21 days during radiotherapy or etoposide IV on days 1 to 5 and days 29 to 33 followed by cisplatin IV on days 1, 8, 29, and 36 or pemetrexed IV followed by cisplatin IV every 21 days during radiotherapy. Patients then receive consolidation durvalumab IV every 2 or 4 weeks for up to one year or osimertinib PO QD in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT during follow-up.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a safety analysis of 6 patients with locally advanced esophageal cancer, the combination of pemetrexed, carboplatin, and radiation followed by surgery showed a favorable safety profile, with only one patient experiencing a severe adverse event (grade 4 neutropenia).

The treatment resulted in promising outcomes, with one patient achieving a complete pathologic response and three showing partial responses, indicating potential efficacy that warrants further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed, Carboplatin, and Concomitant Radiation followed by Surgery for Locally Advanced Esophageal Cancer: Results of a Planned Interim Toxicity Analysis of North Central Cancer Treatment Group Study N044E. Katipamula, R., Jatoi, A., Foster, NR., et al.[2021]

Pemetrexed (Alimta) is an effective treatment for mesothelioma and shows comparable survival rates to docetaxel in advanced non-small-cell lung cancer (NSCLC) while causing significantly fewer and less severe side effects.

In combination with platinum agents, pemetrexed has demonstrated significant activity and a favorable toxicity profile, making it a promising option for treating thoracic malignancies and warranting further research with other novel drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in advanced NSCLC: a review of the clinical data. Zinner, RG., Fossella, FV., Herbst, RS.[2015]

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]

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]

Combined chemotherapy with paclitaxel and carboplatin alongside thoracic radiation therapy has shown a clear survival benefit for patients with locally advanced, unresectable non-small cell lung cancer (NSCLC), as demonstrated in randomized trials and meta-analyses.

Ongoing and planned multicenter studies aim to refine treatment regimens and improve both local and systemic control of NSCLC, highlighting the need for a multidisciplinary approach to effectively manage this systemic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporation of paclitaxel and carboplatin in combined-modality therapy for locally advanced non-small cell lung cancer. Belani, CP.[2015]

In a Phase II study involving 55 patients with inoperable non-small-cell lung cancer (NSCLC), a treatment regimen of 74 Gy radiation combined with weekly carboplatin and paclitaxel chemotherapy resulted in a median survival of 25.9 months and a 12-month overall survival rate of 75.5%.

While the treatment showed promising survival outcomes, 12 patients experienced severe lung toxicity, highlighting the need for careful monitoring of side effects in high-dose radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary analysis of the phase II component of a phase I/II dose intensification study using three-dimensional conformal radiation therapy and concurrent chemotherapy for patients with inoperable non-small-cell lung cancer: RTOG 0117. Bradley, JD., Bae, K., Graham, MV., et al.[2021]

The combination of carboplatin and dose-dense pemetrexed with involved field radiotherapy is feasible for treating locally advanced and oligometastatic non-small cell lung cancer (NSCLC), as shown in a phase I study with 18 enrolled patients.

Despite some dose-limiting toxicities observed, the treatment resulted in a median survival time of 28.6 months, with 13 out of 16 evaluable patients showing a local regional response, indicating promising efficacy for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma. Shen, X., Denittis, A., Werner-Wasik, M., et al.[2021]

In a randomized phase 2 trial involving 101 patients with stage IV lung adenocarcinoma, the combination of Pemetrexed and Cisplatin (Pem-Cis) showed a significantly higher one-year survival rate of 72.0% compared to 52.9% for Docetaxel and Cisplatin (Doc-Cis).

Patients receiving Pem-Cis also experienced longer progression-free survival (12.6 months) compared to those on Doc-Cis (7.5 months), indicating that Pem-Cis may be a more effective first-line treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of pemetrexed-cisplatin or docetaxel-cisplatin plus thoracic intensity-modulated radiation therapy in patients with stage IV lung adenocarcinoma. Su, SF., Li, M., Geng, YC., et al.[2020]

Combination therapy using paclitaxel with carboplatin and radiation shows promise as a safer and more effective treatment for non-small cell lung cancer compared to the standard regimen of etoposide and cisplatin.

The use of paclitaxel, a novel taxane drug, in conjunction with radiation therapy may enhance local control of the cancer and improve overall response rates, suggesting a potential advancement in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent paclitaxel, carboplatin, and radiation therapy for locally advanced non-small cell lung cancer. Choy, H., Akerley, W., DeVore, RF.[2015]

Citations

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