Radiation Therapy + Durvalumab for Lung Cancer

Overseen By Erin E Rogers

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Nebraska

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Autoimmune disorders, Uncontrolled illness, Active infection, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 3

43 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is designed to determine if combining consolidative radiation therapy (RT) using a hypofractionated regimen (hfRT) (2 fractions) for boosting the residual primary lung cancer with adjuvant anti-PD-L1 therapy concurrently is safe and will provide better tumor control locoregionally and distantly than either modality alone.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment while participating in this study.

What data supports the effectiveness of the treatment Radiation Therapy + Durvalumab for Lung Cancer?

Research shows that using durvalumab (a type of immunotherapy) after radiation therapy can improve survival rates in patients with advanced lung cancer who cannot have surgery. This combination has become a standard treatment because it helps patients live longer compared to radiation therapy alone. ^{1 2 3 4 5}

Is the combination of radiation therapy and durvalumab safe for humans?

Durvalumab, also known as Imfinzi or MEDI4736, has been studied for safety in various solid tumors, including lung cancer. It is generally considered safe, but some patients may experience side effects like radiation pneumonitis (lung inflammation) when used with radiation therapy. The DUART trial is specifically assessing its safety in patients who cannot undergo chemotherapy. ^{1 2 3 6 7}

How is the treatment of Radiation Therapy + Durvalumab for Lung Cancer different from other treatments?

This treatment combines hypofractionated radiation therapy (hfRT), which delivers higher doses of radiation over fewer sessions, with durvalumab, an immunotherapy drug that helps the immune system attack cancer cells. This combination is particularly beneficial for patients who cannot undergo chemotherapy, offering a potential survival advantage over radiation therapy alone. ^{1 2 3 4 5}

Research Team

Chi Zhang, MD, PhD

Principal Investigator

University of Nebraska

Eligibility Criteria

Adults over 19 with stage III non-small cell lung cancer (NSCLC) who've had or are candidates for chemoradiation therapy. They must have good organ function, an ECOG performance status of 0-1, and a life expectancy over 12 weeks. Women must not be pregnant and participants should agree to birth control measures.

Inclusion Criteria

I am 20 years old or older.

Adequate normal organ and marrow function as defined below: Hemoglobin ≥9.0 g/dL (5.59 mmol/L) (patients can be transfused to meet this criterion), Absolute neutrophil count (ANC) > 1500 per mm3, Platelet count ≥100 x 109/L (>100,000 per mm3), Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN), AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal, Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula, Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause, Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I do not have any serious ongoing illnesses that could affect my participation in the study.

I have previously received treatments targeting my immune system.

I have a history or current infection of TB, hepatitis B, hepatitis C, or HIV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Definitive Chemoradiation Therapy (dCRT)

Participants undergo definitive chemoradiation therapy for stage III NSCLC

6-8 weeks

Consolidative Hypofractionated Radiation Therapy (hfRT) with Durvalumab

Participants receive consolidative hypofractionated radiation therapy and adjuvant anti-PD-L1 therapy with durvalumab

12 months

Bi-weekly visits for durvalumab infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 3 months during durvalumab therapy, then every 4-6 months

Treatment Details

Interventions

• Consolidative Hypofractionated Radiation Therapy (hfRT)
• Durvalumab

Trial Overview The trial tests if combining hypofractionated radiation therapy (hfRT) to target remaining lung cancer with Durvalumab, an anti-PD-L1 drug, is safe and improves tumor control better than either treatment alone.

Participant Groups

Group I: Hypofractionated radiation therapy (hfRT) with Durvalumab Experimental Treatment 2 Interventions

Combining consolidative radiation therapy (RT) using a hypofractionated regimen (hfRT) of 10Gy x 2 fractions for boosting the residual primary lung cancer with adjuvant anti-PD-L1 therapy (durvalumab), dose of 10 mg/kg infusion every two weeks concurrently for up to 12 months or disease progression.

Consolidative Hypofractionated Radiation Therapy (hfRT) is already approved in European Union, United States for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)
• Extensive-stage small cell lung cancer (ES-SCLC)
• Biliary tract cancer (BTC)
• Hepatocellular carcinoma (HCC)
• Endometrial cancer

Approved in United States as Imfinzi for:

• Unresectable Stage III non-small cell lung cancer (NSCLC)
• Extensive-stage small cell lung cancer (ES-SCLC)
• Locally advanced or metastatic biliary tract cancer (BTC)
• Unresectable hepatocellular carcinoma (uHCC)
• Primary advanced or recurrent endometrial cancer

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Chi Zhang

Lead Sponsor

Trials

1

Recruited

40+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In a study of 107 patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT) and intensity-modulated radiotherapy (IMRT), the median progression-free survival (PFS) was 20.7 months, indicating effective treatment outcomes.

Factors associated with longer PFS included a favorable response to CCRT, a radiation dose of 62 Gy or more, and having stage IIIA NSCLC, while shorter durations of durvalumab treatment and lower radiation doses were linked to increased mortality risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study. Takeda, Y., Kusaba, Y., Tsukita, Y., et al.[2022]

In a study of 56 patients with non-small cell lung cancer (NSCLC), those treated with intensity-modulated radiation therapy (IMRT) had a significantly lower incidence of grade 2 or higher radiation pneumonitis (RP) compared to those treated with three-dimensional conformal radiotherapy (3D-CRT), with rates of 27.0% versus 64.0%.

The study identified that the radiation technique (IMRT vs. 3D-CRT) and the volume of lung receiving radiation (V20) were significant risk factors for developing RP, suggesting that IMRT may be a safer option for reducing RP in NSCLC patients undergoing concurrent chemoradiotherapy followed by durvalumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of the incidence of ≥ grade 2 radiation pneumonitis between intensity-modulated radiotherapy and three-dimensional conformal radiotherapy in patients with unresectable non-small cell lung cancer treated with durvalumab after concurrent chemoradiotherapy. Masuo, M., Shinohara, E., Kitano, M., et al.[2023]

The DUART trial is a Phase II study investigating the safety and tolerability of durvalumab in patients with unresectable, stage III non-small-cell lung cancer (NSCLC) who cannot undergo chemotherapy due to poor performance status or other health issues.

This study aims to evaluate whether durvalumab can improve survival outcomes for these patients compared to the current standard of care, which is radiotherapy alone, based on promising results from the PACIFIC trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. Filippi, AR., Dziadziuszko, R., García Campelo, MR., et al.[2022]

In a study of 68 patients with locally advanced non-small cell lung cancer treated with intensity-modulated radiotherapy (IMRT), the administration of durvalumab significantly improved distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS), with hazard ratios of 0.31, 0.33, and 0.32 respectively.

The study also found that while grade 2 or higher radiation pneumonitis (RP) was associated with worse DMFS, reducing the incidence of RP could enhance patient outcomes, highlighting the importance of managing treatment-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice. Yamamoto, T., Tsukita, Y., Katagiri, Y., et al.[2022]

In a study involving 576 patients with unresectable stage III non-small cell lung cancer (NSCLC), the PD-L1 inhibitor durvalumab showed a favorable safety profile, with only 22.7% of patients experiencing adverse events, primarily mild esophagitis.

Durvalumab treatment after concurrent chemoradiotherapy (cCRT) resulted in consistent outcomes across both PD-L1 positive and negative patients, indicating its potential as a standard care option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nationwide Real-Life Safety and Treatment Exposure Data on Durvalumab After Concurrent Chemoradiotherapy in Unresectable Stage III, Locally Advanced, Non-small Cell Lung Cancer: Analysis of Patients Enrolled in the French Early Access Program. Avrillon, V., Daniel, C., Boisselier, P., et al.[2022]

The DEDALUS phase 2 trial is investigating a new treatment approach for 45 patients with unresectable stage III non-small cell lung cancer (NSCLC), combining induction chemo-immunotherapy with de-intensified radiotherapy and the immunotherapy drug durvalumab.

The primary focus of the study is to assess safety by monitoring severe adverse events within 6 months, while secondary goals include evaluating progression-free survival (PFS) and overall survival (OS), indicating a comprehensive approach to understanding both the safety and effectiveness of this treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of a Single-Arm, Phase 2, Multi-Center Study of Chemo-Immunotherapy Followed by Hypo-Fractionated RT and Maintenance Immunotherapy in Patients With Unresectable Stage III NSCLC: The DEDALUS Trial. Filippi, AR., Agustoni, F., Arcangeli, S., et al.[2023]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

A comparison of the incidence of ≥ grade 2 radiation pneumonitis between intensity-modulated radiotherapy and three-dimensional conformal radiotherapy in patients with unresectable non-small cell lung cancer treated with durvalumab after concurrent chemoradiotherapy. [2023]

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

DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice. [2022]

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

Nationwide Real-Life Safety and Treatment Exposure Data on Durvalumab After Concurrent Chemoradiotherapy in Unresectable Stage III, Locally Advanced, Non-small Cell Lung Cancer: Analysis of Patients Enrolled in the French Early Access Program. [2022]

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

Rationale and Design of a Single-Arm, Phase 2, Multi-Center Study of Chemo-Immunotherapy Followed by Hypo-Fractionated RT and Maintenance Immunotherapy in Patients With Unresectable Stage III NSCLC: The DEDALUS Trial. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]