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Non Small Cell Lung CancerPhase 2NCT04003246

Phase II Concurrent Durvalumab and Radiotherapy for for Stage III Non-Small Cell Lung Cancer

A Phase 2 study testing Thoracic RT and Durvalumab and Consolidative Durvalumab in people with Non Small Cell Lung Cancer and Lung Cancer Stage III, run by University of Texas Southwestern Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Single arm, Phase II trial of concurrent Durvalumab (MEDI 4736) and radiotherapy followed by consolidative Durvalumb (MEDI 4736) for Stage III Non-Small Cell Lung Cancer (NSCLC) Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Thoracic RT and Durvalumab and Consolidative Durvalumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
3 Apr 2020to 5 Nov 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1.1 Pathologically (histologically or cytologically) proven diagnosis of NSCLC with, medically inoperable (or patients who refuse resection) stage IIIA or stage IIIB disease (AJCC 8th edition);
  • 1.1.1 Inoperable Stage IIIA disease is defined by multiple and/or bulky N2 mediastinal lymph nodes on computed tomography (CT) scan such that, in the opinion of the treating investigator, the patient was not a candidate for surgical resection.
  • 1.1.2 N2 disease must have been documented by biopsy, or at a minimum by fluorodeoxyglucose positron emission tomography (PET) or CT if nodes were more than 2 cm in short axis diameter.
  • 1.1.3 T4 disease is often considered resectable at the discretion of a thoracic surgeon. Patients with T4N0 or T4N1 disease can be enrolled if their case is reviewed by a thoracic surgeon and felt to be unresectable or if they are either medically inoperable or refuse surgery.
  • 1.1.4 Stage IIIB patients have N3 or T4N2 status. N3 status must have been documented by the presence of a contralateral (to the primary tumor) mediastinal lymph node or supraclavicular or scalene lymph node proven by biopsy, or at a minimum by fluorodeoxyglucose uptake on PET or more than 2 cm in short axis diameter on CT scan. Patients with disease extending into the cervical region (defined as disease extending above cricoid cartilage) are not eligible.
  • 1.2 Appropriate stage for study entry based on the following diagnostic workup:
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  • 1.2.1 History/physical examination, including documentation of height, weight and vital signs, within 30 days prior to registration;
  • 1.2.2 CT scan with IV contrast (CT scan without contrast acceptable if IV contrast is medically contraindicated) of the lung and upper abdomen through the adrenal glands within 60 days prior to registration (recommended within 30 days prior to registration);
  • 1.2.3 MRI of the brain with contrast (or CT with contrast if MRI is medically contraindicated) within 60 days prior to registration; note: the use of intravenous contrast is required for the MRI or CT (unless medically contra-indicated).
  • 1.2.4 Whole-body FDG-PET/CT within 60 days prior to registration;
  • 1.3 Age ≥ 18 years;
  • 1.4 Life expectancy ≥ 12 weeks
  • 1.5 Zubrod Performance Status of 0-1 within 30 days prior to registration;
  • 1.6 Adequate respiratory function within 180 days prior to registration defined as follows: FEV1 > 1.2 liters; DLCO ≥ 50% predicted;
  • 1.7 Patients with post-obstructive pneumonia are eligible provided they no longer require intravenous antibiotics at registration;
  • 1.8 Patients with a pleural effusion that is transudative, cytologically negative and non-bloody, are eligible if the radiation oncologist feels the tumor can be encompassed within a reasonable field of radiotherapy; if pleural fluid is too small a volume to effectively sample by thoracentesis and does not show increased metabolic activity on CT/PET imaging, the patient will be remain eligible.
  • 1.9 Adequate organ and marrow function as defined below
  • 1.9.1 Absolute neutrophil count >1.5 × 10^9/L
  • 1.9.2 Platelet count >100 × 10^9/L
  • 1.9.3 Baseline or post-transfusion Hemoglobin ≥9.0 g/dL
  • 1.9.4 Serum bilirubin≤ 1.5x upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed in consultation with their physician.
  • 1.9.5 Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5x ULN.
  • 1.9.6 Measured creatinine clearance (CL) >40 mL/min or calculated CL >40 mL/min as determined by Cockcroft-Gault (using actual body weight);
  • Males:
  • Creatinine CL = (Weight (kg) × (140 - Age)) / ((mL/min) 72 × serum creatinine (mg/dL))
  • Females:
  • Creatinine CL = (Weight (kg) × (140 - Age) × 0.85) / ((mL/min) 72 × serum creatinine (mg/dL))
  • 1.10 Negative serum pregnancy test within three days prior to registration for women of childbearing potential.
  • 1.11 Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • 1.11.1 A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
  • 1.11.2 Evidence of post-menopausal status or negative urinary or 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. The following age-specific requirements apply:
  • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • 1.12 Ability to understand and the willingness to sign a written informed consent.

Who cannot join

  • 2.1 Definitive clinical or radiologic evidence of metastatic disease;
  • 2.2 Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
  • 2.3 Current invasive malignancy (except non-melanomatous skin cancer, localized bladder and prostate cancer). Carcinoma in situ of the breast, oral cavity, or cervix are permissible regardless of timing;
  • 2.4 Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields. For example, patients with prior breast radiotherapy treatments would likely be excluded;
  • 2.5 Prior systemic treatment with chemotherapy, targeted therapy or an anti-PD-1, anti-PD-L1 including durvalumab, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways for locally advanced NSCLC. Prior chemotherapy and/or targeted therapy as adjuvant or neoadjuvant therapy for earlier-stage lung cancer is permitted as long as it was completed ≥6 months prior to enrollment. No prior anti-PD-1, anti-PD-L1 including durvalumab, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways is permitted.
  • 2.6 A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 7 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease;
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  • 2.7 Severe, active co-morbidity defined as follows:
  • 2.7.1 Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
  • 2.7.2 Active or prior documented autoimmune or inflammatory disorders (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
  • Any chronic skin condition that does not require systemic therapy
  • 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
  • 2.7.3 Active infection including tuberculosis, hepatitis B, hepatitis C.
  • 2.7.4 History of allogenic organ transplantation.
  • 2.7.5 History of symptomatic or previously established interstitial lung disease;
  • 2.7.6 History of severe hypersensitivity reaction to any monoclonal antibody or allergy to study drug components;
  • 2.7.7 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.
  • 2.8 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
  • 2.9 Pregnancy, nursing females, or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
  • 2.10 Patients whose radiation treatment plans are likely to encompass a volume of whole lung receiving ≥ 35% of lung volume. V20s up to 37% will be permitted and viewed as a minor deviation, provided that the treating radiation oncologist believes this level of exposure is within patient tolerance.
  • 2.11 Planned radiation cardiac dose V50 >25%.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

    Dallas, Texas, 75390

Other trials in United States

About this study

Official title: Phase II Concurrent Durvalumab (MEDI4736) and Radiotherapy Followed by Consolidative Durvalumab (MEDI4736) for Stage III Non-Small Cell Lung Cancer (NSCLC)

Single arm, Phase II trial of concurrent Durvalumab (MEDI 4736) and radiotherapy followed by consolidative Durvalumb (MEDI 4736) for Stage III Non-Small Cell Lung Cancer (NSCLC)

Read the detailed description

Immunotherapy has significantly improved the survival outcomes of patients with various cancer types including thoracic malignancies. In the PACIFIC study, patients with locally advanced NSCLC were randomized to the anti-PDL1 antibody durvalumab or placebo for up to 12 months after completion of concurrent chemoradiation. While NSCLC is typically considered relatively non-immunogenic, RT is thought to augment tumor immunogenicity(Iyengar \& Gerber, 2013). The abscopal effect refers to the observation that the benefit seen in PACIFIC, along with the growing role of immunotherapy for the treatment advanced (stage IV) NSCLC, suggests that earlier exposure to durvalumab may improve outcomes and be well tolerated, thereby permitting de-escalation of therapy through removal of conventional chemotherapy from these regimens to a local area results in an antitumor effect distant to the radiation site.

Durvalumab (Imfimzi; MEDI4736; AstraZeneca) is a human monoclonal antibody of the immunoglobulin (Ig) G1 kappa subclass that inhibits binding of PD-L1 (B7-H1, CD274) to PD-1 (CD279) and CD80 (B7-1). MEDI4736 is composed of 2 identical heavy chains and 2 identical light chains, with an overall molecular weight of approximately 149 kDa. MEDI4736 contains a triple mutation in the constant domain of the Ig G1 heavy chain that reduces binding to complement protein C1q and the Fcγ receptors involved in triggering effector function. Durvlumab binds with high affinity and specificity to human PD-L1 and blocks its interaction with PD-1 and CD80

Being tested
Thoracic RT and Durvalumab, Consolidative Durvalumab
Keywords
Lung
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Thoracic RT and DurvalumabRadiation

    Also called 3D Conformal Radiation Therapy (3D-CRT), Intensity-Modulated Radiation Therapy (IMRT), Image-Guided Radiation Therapy (IGRT), Imfinzi

    1500mg every 4 weeks [Q4W] intravenous [IV], first dose within 3 days of RT initiation

  • Consolidative DurvalumabDrug

    Also called Imfinzi

    1500mg every 4 weeks [Q4W] intravenous [IV] up to one year

Study groups in NCT04003246
Study groupRoleWhat they receive
Single Arm: Therapeutic InterventionExperimentalAll subjects receive the same therapeutic intervention of 1500mg intravenous durvalumab once every 4 weeks while receiving a 60 Gy/30 Fraction course of thoracic radiotherapy. After radiotherapy is complete, subjects continue to receive 1500mg intravenous durvalumab once every 4 weeks for up to one year following the start of treatment.
Receives: Radiation: Thoracic RT and Durvalumab; Drug: Consolidative Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 12-Month Progression-free Survival (PFS) Time

    To determine the 12-month progression-free survival (PFS) for Stage III non-small cell lung cancer patients treated with concurrent durvalumab and radiotherapy followed by consolidative durvalumab. PFS rate is based on an assessment by an investigator according to RECIST 1.1 criteria; PFS is defined as the time from the study enrollment to documented progressive disease or death due to any cause, whichever occurs first.

    Measured: Twelve months from the study enrollment

Secondary outcomes (4)

  1. Safety and Tolerability

    To assess the safety and tolerability of concurrent durvalumab and radiotherapy compared to historical data from patients treated with standard of care chemo-radiation using adverse event according to CTCAE V.5

    Measured: 4 years from study enrollment

  2. Overall Survival

    To determine the overall survival (OS) defined as the time from study enrollment to death due to any cause

    Measured: Up to 4 years (1461 days) from study enrollment

  3. Distant Metastases Free Survival Time

    Time from study enrollment to any new distant lesion.

    Measured: From date of study enrollment until the date of first documented new distant lesion or date of death from any cause, whichever came first, assessed to the end of the study (approximately 55 months).

  4. Local and Regional Control Time

    The time from the study enrollment to any local and regional lesion.

    Measured: From date of study enrollment until the date of first documented local and regional lesion, assessed to the end of the study (approximately 55 months).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jul 2019
  2. Study start3 Apr 2020
  3. Primary completion15 Jun 2022
  4. Study completion5 Nov 2024

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Patient registration Stage III non-small cell lung cancer Zubrod 0 or 1
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04003246
Sponsor's protocol ID
STU-2019-1082
Status last verified
Mar 2025
First submitted
26 Jun 2019
Last updated
21 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Thoracic RT and Durvalumab and Consolidative Durvalumab in people with Non Small Cell Lung Cancer and Lung Cancer Stage III, run by University of Texas Southwestern Medical Center 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 36 inclusion and 23 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: finished, as of the sponsor's last update on 21 Mar 2025. 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 phase mean?

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?

Yes. Results are posted in the registry (first posted 21 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

12-Month Progression-free Survival (PFS) Time (time frame: Twelve months from the study enrollment). 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 NCT04003246.

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 21 Mar 2025.

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