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

NCT04003246 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: STU-2019-1082
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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)

Conditions

Non Small Cell Lung Cancer; Lung Cancer Stage III

Keywords

Lung

Outcome Measures

Primary Outcomes (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.

  Twelve months from the study enrollment

Secondary Outcomes (4)

• Safety and Tolerability

  4 years from study enrollment

• Overall Survival

  Up to 4 years (1461 days) from study enrollment

• Distant Metastases Free Survival Time

  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).

• Local and Regional Control Time

  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).

Study Arms (1)

Single Arm: Therapeutic Intervention

EXPERIMENTAL

All 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.

Radiation: Thoracic RT and Durvalumab; Drug: Consolidative Durvalumab

Interventions

Thoracic RT and Durvalumab RADIATION

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

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

Single Arm: Therapeutic Intervention

Consolidative Durvalumab DRUG

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

Also known as: Imfinzi

Single Arm: Therapeutic Intervention

Eligibility Criteria

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

You may qualify if:

• 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);
• 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.
• 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.
• 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.
• 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.
• Appropriate stage for study entry based on the following diagnostic workup:
• History/physical examination, including documentation of height, weight and vital signs, within 30 days prior to registration;
• 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);
• 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).
• Whole-body FDG-PET/CT within 60 days prior to registration;
• Age ≥ 18 years;
• Life expectancy ≥ 12 weeks
• Zubrod Performance Status of 0-1 within 30 days prior to registration;
• Adequate respiratory function within 180 days prior to registration defined as follows: FEV1 \> 1.2 liters; DLCO ≥ 50% predicted;
• Patients with post-obstructive pneumonia are eligible provided they no longer require intravenous antibiotics at registration;

You may not qualify if:

• Definitive clinical or radiologic evidence of metastatic disease;
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• 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;
• 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;
• 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.
• 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;
• Severe, active co-morbidity defined as follows:
• 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.
• 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
• Active infection including tuberculosis, hepatitis B, hepatitis C.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• AstraZeneca: collaborator

Study Sites (1)

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

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

durvalumab; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Radiotherapy, Image-Guided

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Dr. Yuanyuan Zhang
• Organization: University of Texas Southwestern Medical Center

yuanyuan.zhang@utsouthwestern.edu

2146458525

Study Officials

• Yuanyuan Zhang, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: Patient registration Stage III non-small cell lung cancer Zubrod 0 or 1

Study Record Dates

• First Submitted: June 26, 2019
• First Posted: July 1, 2019
• Study Start: April 3, 2020
• Primary Completion: June 15, 2022
• Study Completion: November 5, 2024
• Last Updated: March 21, 2025
• Results First Posted: March 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)