Intense Radiation + Chemotherapy for Lung Cancer

Not currently recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Proton Collaborative Group

Disqualifiers: Distant metastasis, Prior thoracic radiotherapy, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for non-small cell lung cancer, using both chemotherapy and a special type of radiation therapy called hypofractionated proton therapy. This radiation method delivers higher doses in a shorter time, aiming to be more effective against cancer. The trial seeks individuals diagnosed with this type of lung cancer within the past few months who have been advised that surgery isn’t a suitable option. Participants should not have cancer that has spread to distant parts of the body and should not have received prior radiation treatment to the chest.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

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 this with the study team or your doctor.

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

Research has shown that using chemotherapy alongside other treatments is generally safe for treating non-small-cell lung cancer. Studies indicate that patients typically survive about 18 months, though this can vary, with some living longer without their cancer worsening. Like all treatments, it can have side effects, but it remains a common and well-established method for treating lung cancer.

Hypofractionated proton therapy is a newer type of radiation treatment. Early research suggests it is safe and effective for lung cancer. For example, one study found that only about 7% of patients experienced severe side effects from the radiation. This therapy delivers higher doses of radiation over a shorter period, which might be more convenient for patients.

Both treatments have been studied separately and are generally well-tolerated. However, researchers are still investigating their combined effects in clinical trials to fully understand their impact together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of intense radiation and chemotherapy for lung cancer because it introduces hypofractionated proton therapy, which is a unique approach to delivering radiation. Unlike traditional radiation therapy that administers small doses over a longer period, hypofractionated proton therapy delivers higher doses in fewer sessions, potentially reducing overall treatment time. Additionally, proton therapy is more precise, targeting tumors with minimal damage to surrounding healthy tissue. This precision could lead to fewer side effects and improved outcomes compared to standard treatments like conventional radiotherapy.

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

Studies have shown that hypofractionated proton therapy combined with chemotherapy, which participants in this trial will receive, offers a promising approach to treating lung cancer. This therapy delivers strong radiation in fewer sessions, effectively targeting different types of lung tumors. Research indicates it works well for lung cancers located in various parts of the lungs. Specifically, previous patients experienced better tumor control with this therapy compared to traditional radiation. These findings suggest it could be a safe and effective treatment option for lung cancer patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Brad Hoppe, MD

Principal Investigator

Proton Collaborative Group

Are You a Good Fit for This Trial?

This trial is for adults with stage II-III non-small cell lung cancer who can't have surgery. They should be in good physical condition, not pregnant, willing to use contraception, and haven't lost a lot of weight recently. No prior chest radiation or evidence of cancer spread far from the lung is allowed.

Inclusion Criteria

Patient must complete all required tests in section 4.

Your lab test results must be from within the 4 weeks before you join the study.

Your white blood cell count must be higher than 1,800 cells/mm3.

Exclusion Criteria

I have had radiation therapy to my chest area before.

I have lost more than 10% of my weight without trying in the last month.

I am not pregnant or breastfeeding and willing to use contraception during and for 12 months after the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hypofractionated proton therapy with concurrent chemotherapy

6-8 weeks

Weekly visits for radiation treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Concurrent Chemotherapy
• Hypofractionated Proton Therapy

Trial Overview The study tests if giving higher daily doses of proton radiation therapy over fewer days (hypofractionation) combined with standard chemotherapy works better for treating non-small cell lung cancer than current methods.

How Is the Trial Designed?

Group I: Proton Radiotherapy with Chemotherapy Experimental Treatment 1 Intervention

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

Approved in United States as Concurrent Chemotherapy for:

• Locally advanced cervical cancer

Approved in Canada as Concurrent Chemotherapy for:

• Locally advanced cervical cancer

Approved in European Union as Concurrent Chemotherapy for:

• Locally advanced cervical cancer

Who Is Running the Clinical Trial?

Proton Collaborative Group

Lead Sponsor

Trials

10

Recruited

41,100+

Published Research Related to This Trial

In a study of 20 patients with central lung cancer treated with high total dose hypofractionated proton beam therapy, there were no severe toxicities (Grade 3 or higher), indicating a strong safety profile for this treatment approach.

The therapy resulted in a 2-year overall survival rate of 73.8% and a local control rate of 78.5%, demonstrating its efficacy, especially in operable patients who had a 100% survival rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Dose Hypofractionated Proton Beam Therapy is a Safe and Feasible Treatment for Central Lung Cancer. Ono, T., Yabuuchi, T., Nakamura, T., et al.[2019]

In a phase 1/2 trial involving 28 patients with locally advanced non-small cell lung cancer (NSCLC), hypofractionated proton therapy combined with chemotherapy resulted in impressive 1-year overall survival rates of 89%, significantly higher than the 62% benchmark from previous studies.

The treatment was well-tolerated, with no severe esophagitis and only 14% of patients experiencing significant radiation-related pulmonary toxicity, suggesting that proton therapy may offer a safer alternative for patients with advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiation with Hypofractionated Proton Therapy in Stage II-III Non-Small Cell Lung Cancer: A Proton Collaborative Group Phase 2 Trial. Hoppe, BS., Nichols, RC., Flampouri, S., et al.[2022]

In a study of 111 patients with early-stage lung cancer, hypofractionated proton beam therapy showed improved overall survival rates with higher doses, achieving a 4-year overall survival of 51% at the 70 Gy dose level.

The treatment was well-tolerated, with no significant complications from radiation pneumonitis, and pulmonary function remained stable one year after therapy, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose hypofractionated proton beam radiation therapy is safe and effective for central and peripheral early-stage non-small cell lung cancer: results of a 12-year experience at Loma Linda University Medical Center. Bush, DA., Cheek, G., Zaheer, S., et al.[2018]

The phase 1 trial involving 18 patients with stage II or III non-small cell lung cancer demonstrated that hypofractionated proton therapy combined with chemotherapy has an acceptable safety profile, with no severe adverse events attributed to radiation therapy.

The study did not identify a maximum tolerated dose, and while two severe adverse events occurred, they were linked to chemotherapy rather than the proton therapy, suggesting that this treatment approach is safe for further investigation in phase 2 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated Proton Therapy with Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Trial from the University of Florida and Proton Collaborative Group. Hoppe, BS., Nichols, RC., Flampouri, S., et al.[2021]

Accelerated hypofractionated radiotherapy (AHR) combined with chemotherapy showed a high overall response rate of 82% in patients with locally advanced non-small-cell lung cancer (NSCLC), indicating its efficacy as a treatment option.

Despite some acute side effects, including severe neutropenia in 70% of patients, the treatment was generally well-tolerated, with no severe long-term side effects reported, suggesting it is a feasible and acceptable approach for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated hypofractionated radiotherapy plus chemotherapy for inoperable locally advanced non-small-cell lung cancer: final results of a prospective phase-II trial with a long-term follow-up. Parisi, E., Genestreti, G., Sarnelli, A., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10912465/

Prospective study investigating hypofractionated proton beam ... Hypofractionated PBT was a safe treatment option for inoperable early stage NSCLC and appeared to be appropriate for small tumor volumes.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23845845/

High-dose hypofractionated proton beam radiation therapy ... Conclusions: High-dose hypofractionated proton therapy achieves excellent outcomes for lung carcinomas that are peripherally or centrally located. The 70-Gy ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0305737222001335

Hypofractionated proton therapy for non-small cell lung ... Hypofractionated PBT is a safe and effective treatment option for ES-NSCLC; the delivery of BED ≥ 105.6 Gy(RBE) with advanced techniques for uncertainty ...

4. cancertreatmentreviews.com cancertreatmentreviews.com/article/S0305-7372(22)00133-5/abstract

Hypofractionated proton therapy for non-small cell lung ... Hypofractionated proton beam radiotherapy (PBT) is gaining attention in early-stage non-small cell lung cancer (ES-NSCLC). However, there is a large unmet ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0012369215312976

Hypofractionated Proton Beam Radiotherapy for Stage I ... Local tumor control appears to be improved when compared to historical results utilizing conventional radiotherapy, with a good expectation of disease-specific ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12433024/

Treatment outcomes and safety of concurrent ... Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with unresectable stage III non-small-cell lung cancer (NSCLC) ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925000474

Efficacy and safety of immune checkpoint inhibition ... With cCRT, progression-free survival (PFS) and overall survival (OS) rates at 5 years were 18–19 % and 16–32 %, respectively [3], [4].

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40950893/

Treatment outcomes and safety of concurrent ... Treatment outcomes and safety of concurrent chemoradiation in older adults with unresectable stage III non-small-cell lung cancer. J Thorac ...

9. biomedical-engineering-online.biomedcentral.com biomedical-engineering-online.biomedcentral.com/articles/10.1186/s12938-025-01390-9

Concurrent vs. sequential chemoradiotherapy: a survival ... Some other studies have shown that CCRT have better overall efficacy in treating lung cancer than SCRT [13]. However, there may be differences ...

10. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)37779-8/fulltext

Outcomes of concurrent chemoradiotherapy in patients ... Median overall survival was 18.2 months [95% confidence interval (CI) 13.1–23.3 months]. Independent prognostic factors for overall survival were PS (0 versus ≥ ...