Lung CancerPhase 1/2NCT04748419
Safety & Efficacy of Consolidative Hypofractionated Radiation Therapy for Boosting Residual Lung Cancer With Durvalumab
A Phase 1/2 study testing consolidative hypofractionated radiation therapy (hfRT) and Durvalumab 50 MG/ML in people with Lung Cancer and Carcinoma, Non-Small Cell Lung, run by University of Nebraska at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Lung Cancer, Carcinoma, Non-Small Cell Lung
- What is being tested?
- consolidative hypofractionated radiation therapy (hfRT) and Durvalumab 50 MG/ML
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jul 2021to 26 Sep 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically diagnosed NSCLC (squamous cell carcinoma, adenocarcinoma, large- cell carcinoma, or non-small-cell lung cancer not otherwise specified), clinical stage III (AJCC 8th Ed.))
- At time of consent, potential subjects must be a candidate for dCRT OR Must have received dCRT with at least 2 cycles of platinum-based chemotherapy concurrent with conventional fractionated radiation therapy with a total dose of 5700 - 6300 cGy
- Patients must be aware of the nature of his/her disease and willingly provide written, informed consent. Including compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
- Age > 19 years at time of study entry
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at time of enrollment.
- Life expectancy of > 12 weeks
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- 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
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4
- Participation in another clinical study with an investigational product during the last 4 weeks
- Concurrent enrolment in another clinical study, unless it is an observational (non- interventional) clinical study or during the follow-up period of an interventional study
- Mixed small cell and non-small cell lung cancer histology
- Patients who receive sequential chemoradiation therapy for locally advanced NSCLC
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- Patients with locally advanced NSCLC who have progressed during definitive platinum based, concurrent chemoradiation therapy
- Any unresolved toxicity NCI CTCAE Grade >2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
- Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician. For example, post-operative neurological deficits for previous benign brain tumors, urinary incontinence from radical prostectomy for prostate cancer, peripheral neuropathy from chemotherapy for breast cancer.
- Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- Major surgical procedure (as defined by the investigator) within 28 days to the first dose of immunotherapy (excluding the placement of vascular access) that would prevent administration of study drug or radiation therapy.
- History of allogenic organ transplantation.
- Active or prior documented autoimmune or inflammatory disorders within the past 2 years (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome stable on hormone replacement or Graves' disease).
- Any chronic skin condition including psoriasis that does not require systemic therapy (within the past 2 years).
- Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
- Patients with celiac disease controlled by diet alone.
- Known allergy or hypersensitivity to Durvalumab or any excipient.
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
- History of another primary malignancy except for
- Malignancy treated with curative intent and with no known active disease ≥5 years before the informed consent and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
- History of primary immunodeficiency
- Known history or active infection of tuberculosis, hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies).
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
- Systemic corticosteroids at doses ≤10 mg/day of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- Systemic steroid administration required to manage toxicities arising from radiation therapy delivered as part of the chemoradiation therapy for locally advanced NSCLC is allowed.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab therapy.
- Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
- Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
- Previous history of RT (other than RT as part of the dCRT for the current course of NSCLC) involving any part of lungs, chest wall, thoracic spine or breast(s).
- Judgment by the investigator that the patient is unsuitable to participate in the study for any condition and the patient is unlikely to comply with study procedures, restrictions and requirements.
- Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (2-5 minutes apart). Triplicate ECGs should only be performed if screening ECG shows QTcF ≥470 ms.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: Phase I/II Study Assessing Safety & Efficacy of Consolidative Hypofractionated Radiation Therapy for Boosting Residual Primary Lung Cancer With Durvalumab After Definitive Chemoradiation Therapy for Stage III Non-small Cell Lung Cancer
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.
Read the detailed description
For safety reasons, consolidative hfRT will start from 6.5Gy x 2 fractions and dose escalate to 10Gy x 2 fractions in a 3+3 design. Consolidative hfRT will be delivered one to two months after finishing definitive chemoradiation therapy (dCRT) and concurrently with adjuvant anti-PD-L1 therapy using durvalumab in stage III non-small cell lung cancer (NSCLC).
At the final determined consolidative hfRT dose level, a total of thirty-two subjects with pathologically documented stage III NSCLC treated with dCRT will be enrolled for data analyses.
Follow-up assessments will occur every 3 months during durvalumab therapy for the first two years, then every 4-6 months after 2 years from study registration until confirmed disease progression or death. Primary endpoints include the safety of boost hfRT and concurrent anti-PD-L1 therapy adjuvantly following dCRT, and the 12-month progression-free survival to compare with historical results.
- Conditions
- Lung Cancer, Carcinoma, Non-Small Cell Lung
- Being tested
- consolidative hypofractionated radiation therapy (hfRT), Durvalumab 50 MG/ML
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
consolidative hypofractionated radiation therapy (hfRT)Radiation
Consolidative hfRT will start from 6.5Gy x 2 fractions and dose escalate to 10Gy x 2 fractions in a 3+3 design
Durvalumab 50 MG/MLDrug
Also called Imfinzi
Durvalumab 10 mg/kg via a 60-minute iv infusion every two weeks ± 3 days for up to 12 months
| Study group | Role | What they receive |
|---|---|---|
| Hypofractionated radiation therapy (hfRT) with Durvalumab | Experimental | 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. Receives: Radiation: consolidative hypofractionated radiation therapy (hfRT); Drug: Durvalumab 50 MG/ML |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the safety of combining hfRT and durvalumab by Adverse event assessed
Adverse events (AEs) will be assessed during the entire course of study
Measured: 2 years
Evaluate progression free survival (PFS) when combining hfRT with adjuvant anti-PD-L1 therapy (durvalumab)
based on assessments according to RECIST 1.1
Measured: 12-month
Secondary outcomes (2)
Progression Free survival (PFS) when combining hfRT with adjuvant anti-PD-L1 therapy
PFS based on assessments according to RECIST 1.1a
Measured: 18 months
Overall Survival hfRT and adjuvant anti-PD-L1 therapy
Overall Survival when combining hfRT with adjuvant anti-PD-L1 therapy
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2021
- Study start15 Jul 2021
- Primary completion26 Sep 2025
- Study completion26 Sep 2025
Why it stopped: Poor accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Apar Ganti, MD, MS, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04748419
- Sponsor's protocol ID
- 0004-21-FB
- Status last verified
- Nov 2025
- First submitted
- 5 Feb 2021
- Last updated
- 5 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Coutu B, Lawrence E, Ganti AK, Marr A, Wichman C, Zhang C. Phase I/II study to evaluate consolidative hypofractionated radiation therapy for boosting the residual primary disease in combination with durvalumab after definitive chemoradiation therapy for stage III non-small cell lung cancer (NSCLC): study protocol for a prospective trial. J Thorac Dis. 2024 Jan 30;16(1):750-759. doi: 10.21037/jtd-23-304. Epub 2024 Jan 29.
PubMed 38410608
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study Assessing Safety & Efficacy of Consolidative Hypofractionated Radiation Therapy for Boosting Residual Primary Lung Cancer With Durvalumab After Definitive Chemoradiation Therapy for Stage III Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT04748419
- Acronym / sponsor ID
- 0004-21-FB
- Conditions
- Lung Cancer, Carcinoma, Non-Small Cell Lung
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 15 Jul 2021 (actual)
- Primary completion
- 26 Sep 2025 (actual)
- Study completion
- 26 Sep 2025 (actual)
- First posted
- 10 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
For safety reasons, consolidative hfRT will start from 6.5Gy x 2 fractions and dose escalate to 10Gy x 2 fractions in a 3+3 design. Consolidative hfRT will be delivered one to two months after finishing definitive chemoradiation therapy (dCRT) and concurrently with adjuvant anti-PD-L1 therapy using durvalumab in stage III non-small cell lung cancer (NSCLC).
At the final determined consolidative hfRT dose level, a total of thirty-two subjects with pathologically documented stage III NSCLC treated with dCRT will be enrolled for data analyses.
Follow-up assessments will occur every 3 months during durvalumab therapy for the first two years, then every 4-6 months after 2 years from study registration until confirmed disease progression or death. Primary endpoints include the safety of boost hfRT and concurrent anti-PD-L1 therapy adjuvantly following dCRT, and the 12-month progression-free survival to compare with historical results.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hypofractionated radiation therapy (hfRT) with Durvalumab | Experimental | Radiation: consolidative hypofractionated radiation therapy (hfRT), Drug: Durvalumab 50 MG/MLCombining 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. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Pathologically diagnosed NSCLC (squamous cell carcinoma, adenocarcinoma, large- cell carcinoma, or non-small-cell lung cancer not otherwise specified), clinical stage III (AJCC 8th Ed.))
- At time of consent, potential subjects must be a candidate for dCRT OR Must have received dCRT with at least 2 cycles of platinum-based chemotherapy concurrent with conventional fractionated radiation therapy with a total dose of 5700 - 6300 cGy
- Patients must be aware of the nature of his/her disease and willingly provide written, informed consent. Including compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
- Age > 19 years at time of study entry
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at time of enrollment.
Key exclusion criteria (39 listed)
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4
- Participation in another clinical study with an investigational product during the last 4 weeks
- Concurrent enrolment in another clinical study, unless it is an observational (non- interventional) clinical study or during the follow-up period of an interventional study
- Mixed small cell and non-small cell lung cancer histology
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| consolidative hypofractionated radiation therapy (hfRT)Consolidative hfRT will start from 6.5Gy x 2 fractions and dose escalate to 10Gy x 2 fractions in a 3+3 design | Radiation | Hypofractionated radiation therapy (hfRT) with Durvalumab |
| Durvalumab 50 MG/MLAlso: ImfinziDurvalumab 10 mg/kg via a 60-minute iv infusion every two weeks ± 3 days for up to 12 months | Drug | Hypofractionated radiation therapy (hfRT) with Durvalumab |
Primary outcome
Evaluate the safety of combining hfRT and durvalumab by Adverse event assessed
Time frame: 2 years
Adverse events (AEs) will be assessed during the entire course of study
Evaluate progression free survival (PFS) when combining hfRT with adjuvant anti-PD-L1 therapy (durvalumab)
Time frame: 12-month
based on assessments according to RECIST 1.1
2 secondary outcomes
Progression Free survival (PFS) when combining hfRT with adjuvant anti-PD-L1 therapy
Time frame: 18 months
Overall Survival hfRT and adjuvant anti-PD-L1 therapy
Time frame: 12 months
Results and safety
The study was stopped early (reason given: Poor accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2026.
- Derived from this study: PubMed 38410608Coutu B, Lawrence E, Ganti AK, Marr A, Wichman C, Zhang C. Phase I/II study to evaluate consolidative hypofractionated radiation therapy for boosting the residual primary disease in combination with durvalumab after definitive chemoradiation therapy for stage III non-small cell lung cancer (NSCLC): study protocol for a prospective trial. J Thorac Dis. 2024 Jan 30;16(1):750-759. doi: 10.21037/jtd-23-304. Epub 2024 Jan 29.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Apar Ganti, MD, MS principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing consolidative hypofractionated radiation therapy (hfRT) and Durvalumab 50 MG/ML in people with Lung Cancer and Carcinoma, Non-Small Cell Lung, run by University of Nebraska at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Poor accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the safety of combining hfRT and durvalumab by Adverse event assessed (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04748419, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2026; AzTrials last refreshed its copy on 8 Nov 2026.