Safety & Efficacy of Consolidative Hypofractionated Radiation Therapy for Boosting Residual Lung Cancer With Durvalumab

NCT04748419 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 0004-21-FB
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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 modality alone.

Conditions

Lung Cancer; Carcinoma, Non-Small Cell Lung

Outcome Measures

Primary Outcomes (2)

• Evaluate the safety of combining hfRT and durvalumab by Adverse event assessed

  Adverse events (AEs) will be assessed during the entire course of study

  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

  12-month

Secondary Outcomes (2)

• Progression Free survival (PFS) when combining hfRT with adjuvant anti-PD-L1 therapy

  18 months

• Overall Survival hfRT and adjuvant anti-PD-L1 therapy

  12 months

Study Arms (1)

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.

Radiation: consolidative hypofractionated radiation therapy (hfRT); Drug: Durvalumab 50 MG/ML

Interventions

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

Hypofractionated radiation therapy (hfRT) with Durvalumab

Durvalumab 50 MG/ML DRUG

Durvalumab 10 mg/kg via a 60-minute iv infusion every two weeks ± 3 days for up to 12 months

Also known as: Imfinzi

Hypofractionated radiation therapy (hfRT) with Durvalumab

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• Patients with locally advanced NSCLC who have progressed during definitive platinum based, concurrent chemoradiation therapy
• 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).

Sponsors & Collaborators

• University of Nebraska: lead
• AstraZeneca: collaborator

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Related Publications (1)

• 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.

  PMID: 38410608 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Chi Zhang, MD, PhD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2021
• First Posted: February 10, 2021
• Study Start: July 15, 2021
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: January 22, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)