Hypo-fractionated vs Standard IMRT with Chemotherapy and Immunotherapy for Non-Small Cell Lung Cancer

Recruiting at 6 trial locations

Overseen By KUCC Navigation

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Kansas Medical Center

Must not be taking: Anti-neoplastic, Investigational agents

Disqualifiers: Psychiatric illness, Severe systemic disease, others

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

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

Compensation: Varies

Number of Visits: 6

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two types of radiation treatments combined with chemotherapy and immunotherapy to determine which is more effective for advanced non-small cell lung cancer (NSCLC). One group receives a shorter, more intense radiation schedule called Hypo-Fractionation, while the other follows a standard radiation schedule. Researchers aim to discover if the shorter schedule improves cancer control in the lung area. Eligible participants have Stage IIIA or IIIB NSCLC with no signs of cancer spreading to other parts of the body or brain. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings in cancer treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot use other anti-cancer or investigational drugs while participating in this study.

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

Research shows that hypofractionated radiation therapy, which involves larger doses of radiation in fewer sessions, is generally well-tolerated by patients with non-small cell lung cancer. Studies have found that this treatment delivers a lower dose to nearby organs like the lungs, heart, and esophagus, reducing the risk of side effects.

The chemotherapy drugs carboplatin and paclitaxel are commonly used and have well-known side effects, such as tiredness, nausea, and lower blood counts, but these are usually manageable.

Durvalumab, an immunotherapy drug used after radiation and chemotherapy, is known for its safety and is already approved for some lung cancer patients, indicating its suitability for wider use.

In summary, while all treatments can have side effects, current evidence suggests that the treatments tested in this trial are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore different approaches to radiation therapy for non-small cell lung cancer (NSCLC). The hypo-fractionation method delivers higher doses of radiation over a shorter period (5 weeks), potentially making treatment faster and more convenient compared to the standard fractionation approach, which takes 6 weeks. Both treatment arms include chemotherapy with Paclitaxel and Carboplatin, followed by immunotherapy with Durvalumab, aiming to boost the immune system's ability to fight cancer. This combination of treatments could potentially enhance effectiveness and reduce treatment duration, which is a significant advantage over existing standards of care.

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

This trial will compare hypofractionated radiotherapy with standard-fractionation radiotherapy for treating non-small cell lung cancer (NSCLC). Studies have shown that hypofractionated radiotherapy, which involves delivering higher doses of radiation in fewer sessions, can be effective for NSCLC. This approach often achieves similar results to standard treatments but in a shorter time. Research suggests it might help patients live longer while keeping side effects manageable. In this trial, both treatment arms will combine their respective radiotherapy approaches with chemotherapy and immunotherapy, such as durvalumab, which has shown promise in improving patient outcomes. Overall, interest is growing in using these methods for treating locally advanced NSCLC. ^{1 3 6 7 8}

Who Is on the Research Team?

Krishna Reddy, MD

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

Adults diagnosed with Stage IIIA or IIIB non-small cell lung cancer (NSCLC) who have no brain metastases, negative PET/CT for distant metastasis, and adequate organ function. Women must not be pregnant and agree to contraception. Excluded are those with severe diseases, other treatments, infections, prior thoracic radiotherapy or certain psychiatric/social situations.

Inclusion Criteria

Women who could become pregnant must have a negative pregnancy test within one month before starting treatment.

There is no evidence of cancer spread found in the PET/CT scan.

My organ functions are within normal ranges according to recent tests.

Exclusion Criteria

I do not have severe health issues that would affect the study.

Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements

I am not using, nor plan to use other cancer treatments while in this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Chemotherapy

Participants receive either hypo-fractionated or standard-fractionated IMRT with concurrent chemotherapy (Paclitaxel and Carboplatin) for 5-6 weeks

5-6 weeks

5 visits per week (in-person)

Immunotherapy

Participants receive maintenance Durvalumab, 1500 mg, IV every 4 weeks for 12 months

12 months

1 visit per month (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and long-term outcomes such as locoregional control, survival, and quality of life

Up to 7.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Hypo-Fractionation
• Standard-Fractionation

Trial Overview

The trial is testing if a shorter course of high-dose radiation therapy (hypo-fractionated IMRT) combined with chemotherapy and immunotherapy improves local control of lung cancer compared to the standard longer course (standard-fractionated IMRT), followed by maintenance durvalumab.

How Is the Trial Designed?

Group I: Hypo-Fractionation Experimental Treatment 1 Intervention

Participants will receive one fraction of radiation therapy a day for 5 days each week for 5 weeks along with weekly chemotherapy with Paclitaxel 45 milligram per meter squared (mg/m2) through intravenous (IV)infusion for 1 hour followed by Carboplatin area under the curve (AUC) 2 IV for 30 minutes for approximately 5 or 6 weeks. Once complete, participant will receive Durvalumab, 1500 mg, IV every 4 weeks for 12 months.

Group II: Standard-Fractionation Active Control 1 Intervention

Participants will receive one fraction of radiation therapy a day for 5 days each week for 6 weeks along with weekly chemotherapy with Paclitaxel 45 milligram per meter squared (mg/m2) through intravenous (IV)infusion for 1 hour followed by Carboplatin AUC 2 IV for 30 minutes for approximately 5 or 6 weeks. Once complete, participant will receive Durvalumab, 1500 mg, IV every 4 weeks for 12 months.

Hypo-Fractionation is already approved in United States, European Union for the following indications:

Approved in United States as Hypofractionated Radiation Therapy for:

• Non-Small Cell Lung Cancer (NSCLC)

Approved in European Union as Hypofractionated Radiation Therapy for:

• Non-Small Cell Lung Cancer (NSCLC)

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Published Research Related to This Trial

In a study of 462 breast cancer patients, both Conventional Fractionated Radiotherapy (CFRT) and Hypofractionated Radiotherapy (HFRT) showed similar 5-year loco-regional recurrence-free survival rates of 96.1%, indicating that HFRT is as effective as CFRT for this outcome.

While CFRT had a slightly higher 5-year disease-free survival rate (68.8% vs. 63.5%), the difference was not statistically significant, and both treatments had comparable toxicity profiles, suggesting HFRT is a safe alternative in resource-limited settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Treatment Outcome between Hypofractionated Radiotherapy and Conventional Radiotherapy in Postmastectomy Breast Cancer. Tovanabutra, C., Katanyoo, K., Uber, P., et al.[2020]

In a study of 2159 patients with stage I non-small cell lung cancer, hypofractionated radiotherapy (HFRT) showed a longer overall survival (OS) compared to conventionally fractionated radiotherapy (CFRT) in univariable analysis, but this benefit was not confirmed in multivariable analysis, suggesting that the difference may not be clinically significant.

High-dose HFRT (HD-HFRT) demonstrated a statistically significant improvement in OS compared to CFRT in multivariable analysis, but this finding was not consistent across all sensitivity analyses, indicating that while HD-HFRT may be beneficial, further research is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization and Survival Impact of Hypofractionated Radiotherapy in Stage I Non-small Cell Lung Cancer. Saeed, NA., Jin, L., Amini, A., et al.[2023]

Hypo-fractionation radiotherapy (HFRT) was found to be more effective than conventional radiotherapy (CRT) in suppressing tumor growth in non-small cell lung cancer (NSCLC), as it normalized tumor vasculature and improved hypoxia during a specific 'window-period'.

HFRT's effectiveness is linked to the inhibition of the p-STAT3/HIF-1α signaling pathway, which reduces the expression of angiogenic factors like VEGFA and CXCL12, leading to less tortuous blood vessels and better pericyte coverage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypo-fractionation radiotherapy normalizes tumor vasculature in non-small cell lung cancer xenografts through the p-STAT3/HIF-1 alpha signaling pathway. Tong, F., Xiong, CJ., Wei, CH., et al.[2023]

Hypofractionated radiation therapy (HFRT) significantly reduces the rates of grade ≥2 skin toxicity compared to conventional fractionated radiation therapy (CFRT), with toxicity rates of 28% for HFRT versus 76% for CFRT among 114 patients with early-stage breast cancer.

In patients with larger breast volumes (≥1000 cm³), HFRT still showed lower toxicity rates compared to CFRT, suggesting that HFRT may be a safer option for patients with larger breasts while maintaining similar radiation dose distribution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of breast volume on toxicity using hypofractionated regimens for early stage breast cancer for patients. Butler-Xu, YS., Marietta, M., Zahra, A., et al.[2022]

Hyperfractionation in non-small-cell lung cancer (NSCLC) may improve clinical outcomes for non-metastatic patients, but more mature data is needed before recommending its use outside of clinical trials.

In the palliative treatment of lung cancer, hypofractionation is considered a standard approach, providing effective symptom relief for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altered fractionation radiotherapy in lung cancer. Palazzi, M., Cerrotta, A., Villa, S.[2022]

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]

Hypofractionated radiotherapy (HFRT) for early stage non-small-cell lung cancer (NSCLC) in 26 medically inoperable patients showed a 53.9% overall response rate and a median survival duration of 27.8 months, indicating its efficacy as a treatment option.

The study found that a biologically equivalent dose (BED) greater than 90 Gy was a significant prognostic factor for better progression-free survival and local control, while severe toxicities were not observed, suggesting HFRT is a safe alternative for patients who cannot undergo surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated three-dimensional conformal radiotherapy for medically inoperable early stage non-small-cell lung cancer. Lee, JH., Wu, HG., Kim, HJ., et al.[2021]

Hypofractionated radiation therapy (HypoRT) was found to be effective in treating inoperable advanced non-small cell lung cancer (NSCLC), with an overall response rate of 83% among 30 patients, and a median follow-up of 13 months.

The treatment was well-tolerated, with manageable acute toxicities; however, 37% of patients experienced locoregional recurrence, and 57% developed distant metastasis, indicating the need for further studies to compare HypoRT with conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer. Osti, MF., Agolli, L., Valeriani, M., et al.[2018]

In a phase I study involving 31 patients with advanced lung cancer, the combination of hypofractionated radiotherapy (HFRT) and nivolumab was found to be well tolerated, with no patients developing severe pneumonitis (grade ≥ 3) during a median follow-up of 11 months.

The treatment resulted in an overall objective response rate of 39.13% and a complete remission rate of 13.04%, suggesting that HFRT may enhance the effectiveness of nivolumab and reduce the frequency of its administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and Hypofractionated Radiotherapy in Patients With Advanced Lung Cancer: ABSCOPAL-1 Clinical Trial. Ye, H., Pang, H., Shi, X., et al.[2022]

A study of 349 breast cancer patients showed that hypofractionated radiation therapy (HFRT) is used significantly more at academic centers compared to community-based providers, with usage rates ranging from 28% to 100%.

Implementing a prospective peer review process increased HFRT usage from 66% to 81%, indicating that oversight and education can enhance compliance with HFRT protocols among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Peer Review on Use of Hypofractionated Regimens for Early-Stage Breast Cancer for Patients at a Tertiary Care Academic Medical Center and Its Community-Based Affiliates. Ganju, RG., TenNapel, M., Chen, AM., et al.[2020]

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Accelerated Hypofractionated Radiotherapy for Locally ...

Short term clinical outcomes of accelerated hypofractionated radiotherapy in inoperable non-small cell lung cancer patients. Rep Pract Oncol ...

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Efficacy and Toxicity of Moderately Hypofractionated ...

Moderately Hypo-RT using helical TomoTherapy may improve OS in patients with unresectable stage III NSCLC, while maintaining toxicity rates.

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Study Details | NCT02720614 | Hypofractionated Radiation ...

Compared with conventional fractionated radiotherapy, accelerated hypofractionated radiotherapy can yield higher BED, shorten the total treatment time, and ...

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sciencedirect.com/science/article/abs/pii/S1556086424023530

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