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

Recruiting at401 trial locations

Overseen by Charles B Simone

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: NRG Oncology

Disqualifiers: Prior radiotherapy, Pregnancy, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests whether adding a precise form of radiation therapy to the usual treatment improves outcomes for patients with advanced lung cancer that can't be operated on. The goal is to see if this combination helps patients live longer and prevents cancer from worsening. This form of radiation therapy has shown promise in improving survival rates in patients with various stages of lung cancer.

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.

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

Research shows that combining chemotherapy drugs like paclitaxel and carboplatin with radiation therapy can improve survival rates in patients with advanced non-small cell lung cancer. Studies have demonstrated that these combinations, when used with radiation, offer better outcomes compared to radiation alone. ^{1 2 3 4 5}

Is the combination of high-dose radiation, chemotherapy, and immunotherapy generally safe for humans?

Research shows that combinations of chemotherapy drugs like paclitaxel, carboplatin, and pemetrexed with radiation therapy have been studied for safety in treating non-small cell lung cancer and other cancers. These studies generally found that the treatments were safe, with manageable side effects, although some patients experienced severe side effects like anemia (low red blood cell count) and neutropenia (low white blood cell count). ^{2 3 4 6 7}

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

This treatment is unique because it combines high-dose radiation with chemotherapy and immunotherapy, using a mix of drugs like carboplatin, cisplatin, and durvalumab, which may enhance the body's immune response against cancer. The combination aims to improve local and systemic control of the disease, potentially offering better outcomes than standard chemotherapy and radiation alone. ^{1 2 3 8 9}

Research Team

Charles B Simone

Principal Investigator

NRG Oncology

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Carboplatin (Chemotherapy)
• Cisplatin (Chemotherapy)
• Durvalumab (Immunotherapy)
• Etoposide (Chemotherapy)
• Image Guided Radiation Therapy (Radiation)
• Paclitaxel (Chemotherapy)
• Pemetrexed (Chemotherapy)
• Stereotactic Body Radiation Therapy (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.

Participant Groups

Group I: Arm II (SBRT, image guided RT, chemotherapy, immunotherapy) Experimental Treatment 12 Interventions

Patients undergo SBRT and conventional IGRT and 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 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 11 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 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 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?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

Stephanie Gaillard

NRG Oncology

Chief Medical Officer

MD from Johns Hopkins University

Norman Wolmark

NRG Oncology

Chief Executive Officer since 2023

MD from Harvard Medical School

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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 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]

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]

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 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]

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]

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]

References

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

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

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma. [2021]

4. United States 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. [2020]

5. 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]

6. New Zealand 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. [2021]

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

Pemetrexed in advanced NSCLC: a review of the clinical data. [2015]

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

Concurrent paclitaxel, carboplatin, and radiation therapy for locally advanced non-small cell lung cancer. [2015]

9. United States 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. [2021]