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

Trial Summary

What is the purpose of this trial?

The hypothesis for this study is that hypofractionated IMRT to 62.5 Gy in 25 fractions (2.5 Gy/fraction) with concurrent carboplatin and paclitaxel, followed by maintenance durvalumab will improve locoregional control at 18 months by 10% compared to standard-fractionated chemo-IMRT/durvalumab. A modest improvement in locoregional control (LRC) was selected as a target which could merit further study of this hypofractionated IMRT regimen in a Phase III trial

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.

What data supports the effectiveness of the treatment Hypo-Fractionation, Hypofractionated Radiation Therapy, Hypofractionation, HFRT, Standard-Fractionation, Standard-Fractionation Radiation Therapy, Conventional Fractionation Radiation Therapy for Non-Small Cell Lung Cancer?

Research shows that hypofractionated radiation therapy (HFRT) can improve local control and has a higher biological effect with a shorter treatment time for patients with inoperable advanced stage non-small cell lung cancer (NSCLC). Additionally, studies in early-stage breast cancer suggest that HFRT and conventional radiation therapy have equivalent outcomes, indicating potential effectiveness in other cancers as well. ^{1 2 3 4 5}

Is hypofractionated radiation therapy generally safe for humans?

Research shows that hypofractionated radiation therapy (HFRT) is generally considered safe, with studies in breast cancer patients indicating similar safety profiles to conventional fractionated radiation therapy (CFRT). While specific safety data for non-small cell lung cancer is limited, HFRT has been used safely in other conditions. ^{1 3 4 6 7}

How is the treatment of hypofractionated radiotherapy with chemotherapy and immunotherapy different for non-small cell lung cancer?

This treatment is unique because it uses hypofractionated radiotherapy (HFRT), which delivers higher doses of radiation over fewer sessions compared to standard fractionation, potentially improving tumor control and survival. It is combined with chemotherapy and immunotherapy, which may enhance the overall effectiveness by targeting cancer cells in multiple ways. ^{1 7 8 9 10}

Research Team

Krishna Reddy, MD

Principal Investigator

University of Kansas Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Utilization and Survival Impact of Hypofractionated Radiotherapy in Stage I Non-small Cell Lung Cancer. [2023]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Hypofractionated three-dimensional conformal radiotherapy for medically inoperable early stage non-small-cell lung cancer. [2021]

3. United States 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. [2020]

4. Thailand pubmed.ncbi.nlm.nih.gov

Comparison of Treatment Outcome between Hypofractionated Radiotherapy and Conventional Radiotherapy in Postmastectomy Breast Cancer. [2020]

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

Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer. [2018]

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

The effect of breast volume on toxicity using hypofractionated regimens for early stage breast cancer for patients. [2022]

7. England 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. [2023]

8. England 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. [2020]

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

Nivolumab and Hypofractionated Radiotherapy in Patients With Advanced Lung Cancer: ABSCOPAL-1 Clinical Trial. [2022]

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

Altered fractionation radiotherapy in lung cancer. [2022]