Durvalumab and Stereotactic Radiotherapy for Advanced NSCLC

NCT04786093 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: STU-2021-0171
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized Phase II study which is designed to determine the impact of stereotactic radiotherapy and durvalumab on quality-of-life and oncologic outcomes in patients with advanced non-small cell lung cancer. Durvalumab (Imfinzi) and stereotactic radiotherapy, with each fraction of radiotherapy is given every other day on a standard stereotactic ablative radiotherapy (SAbR) schedule or every four weeks on the personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR) schedule. Subjects will be followed for a period of 2 years after completion of treatment or until death, whichever occurs first. Specifically, subjects will be followed at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months following treatment. After the 2 year follow up, the patient can continue routine follow up with their physicians, per standard of care. Subjects removed from therapy for unacceptable adverse events will be followed until resolution or stabilization of the adverse event.

Conditions

Non Small Cell Lung Cancer

Keywords

Non-small cell lung cancer; Immunotherapy; Durvalumab; Radiation therapy; Radiotherapy; Stereotactic body radiation therapy; Stereotactic ablative radiotherapy; SBRT; SABR; PULSAR

Outcome Measures

Primary Outcomes (1)

• Quality of Life Scores

  To assess the impact of durvalumab and stereotactic radiotherapy, in the form of stereotactic ablative radiotherapy (SAbR) or personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR), on improving QoL (quality of life) in patients with metastatic non-small cell lung cancer using the European organization for Research and treatment of cancer questionnaire (EORTC-QLQ30). The score range is 0-100. Higher the score, the better the results.

  2 years post-treatment

Secondary Outcomes (6)

• Local Control (LC)

  3 months post-treatment

• Out-of-field Control

  3-months post-treatment

• Progression Free Survival (PFS)

  3 months post-treatment

• Overall Survival

  3 months post-treatment

• Overall Response Rate (ORR)

  12 weeks from randomization

Study Arms (2)

Stereotactic Ablative Radiotherapy (SAbR) Arm plus Durvalumab arm

ACTIVE COMPARATOR

SAbR with each radiation treatment fraction delivered every other day

Radiation: Stereotactic radiation therapy; Drug: Durvalumab

Personalized Ultra-fractionated Stereotactic Radiotherapy (PULSAR) plus Durvalumab arm

EXPERIMENTAL

PULSAR with each radiation treatment fraction delivered every 4 weeks

Radiation: Stereotactic radiation therapy; Drug: Durvalumab

Interventions

Stereotactic radiation therapy RADIATION

Radiation therapy will be delivered using standard SAbR treatment schedule or every 4 weeks on the PULSAR schedule to achieve optimal local control of metastatic cancer and augment the effects of durvalumab.

Personalized Ultra-fractionated Stereotactic Radiotherapy (PULSAR) plus Durvalumab arm; Stereotactic Ablative Radiotherapy (SAbR) Arm plus Durvalumab arm

Durvalumab DRUG

Durvalumab (initially developed as MEDI4736) 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 fragment crystallizable gamma receptors involved in triggering effector function.

Personalized Ultra-fractionated Stereotactic Radiotherapy (PULSAR) plus Durvalumab arm; Stereotactic Ablative Radiotherapy (SAbR) Arm plus Durvalumab arm

Eligibility Criteria

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

You may qualify if:

• Patients must have biopsy-proven metastatic non-small cell lung cancer and eligible for receipt of immunotherapy, based on standard of care
• Patients can present with either de novo metastatic disease or recurrent disease
• Patients must have at least one (1) symptomatic or progressive metastatic sites with no more than 10 metastatic sites, based on standard imaging studies
• Patients cannot have received any prior radiation therapy or surgery to the intended radiation treatment area (index lesion)
• Patients with brain metastases may be enrolled if all lesions are treated with radiation therapy or surgery prior to start of protocol therapy
• Metastases in major lower extremity weight-bearing bones or spine should undergo surgical stabilization if indicated
• Age greater than or equal to 18 years.
• Both men and women and members of all races and ethnic groups will be included
• Eastern Cooperative Oncology Group Performance status 0 to 2 (Appendix A)
• Adequate normal organ and bone marrow function as defined by:
• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.0 × 109 /L
• Platelet count ≥75 × 109/L
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
• AST (SGOT)/ALT (SGPT) ≤2.5X institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5X ULN

You may not qualify if:

• 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
• Administration of two or more lines of systemic therapy for the diagnosis of metastatic non-small cell lung cancer
• Prior receipt of systemic therapy for the management of high-risk early stage or locally advanced non-small cell lung cancer, prior to the development of metastatic disease, would not count towards the number of receipt of systemic therapy
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• Patients with untreated brain metastases
• Patients with progressive metastatic disease involving the skin or subcutaneous tissues, esophagus, stomach, intestines, or mesenteric lymph nodes that are felt to be too high risk to treat with radiation therapy to protocol dose.
• Patients cannot have pathologic fracture at the evaluated site
• Patients cannot have untreated spinal cord compression
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab or other agents used in study
• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiosurgery; durvalumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

Large periods time without enrollment while considering protocol changes led to a small number of subjects analyzed prior to study closure.

Results Point of Contact

• Title: Dr. Shahed Badiyan
• Organization: UT Southwestern Medical Center

Shahed.Badiyan@UTSouthwestern.edu

214-648-3638

Study Officials

• Shahed Badiyan, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: We hypothesize that Durvalumab and stereotactic radiotherapy, in the form of PULSAR and SAbR, and durvalumab will confer a 60% increase in improvement in quality of life over the historical control rate of 33%, for an absolute improvement of 27%. Using a two-sided exact binomial test with a two-sided significance level of 0.1 and 80% power, we estimate that we will need to enroll 23 patients per arm do detect a difference. Accounting for 10% attrition, we will plan to enroll 52 patients.

Study Record Dates

• First Submitted: February 28, 2021
• First Posted: March 8, 2021
• Study Start: July 27, 2021
• Primary Completion: June 9, 2022
• Study Completion: June 9, 2022
• Last Updated: May 5, 2026
• Results First Posted: May 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)