Study of Osimertinib and Stereotactic Ablative Radiation (SABR) in EGFR Mutant NSCLC

NCT03667820 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STU 122017-017
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief Summary

This study evaluates the combination of two well-tolerated therapies, osimertinib and Stereotactic Ablative Radiation (SABR).

Conditions

Non-small Cell Lung Cancer (NSCLC)

Outcome Measures

Primary Outcomes (1)

• Determine efficacy of Osimertinib plus SABR in patients with EGFR mutant lung cancer measured by Progression-Free Survival (PFS)

  Progression-Free Survival (PFS) as determined by RECIST 1.1 or death (in the absence of progression).

  Every 8 weeks from the time of first dose of study medication until subject death from any cause, assessed up to 300 weeks.

Secondary Outcomes (6)

• Determine the impact of Osimertinib plus SABR on survival

  From time of first dose of study medication until subject death from any cause, up to 300 weeks.

• Determine the impact of Osimertinib plus SABR on length of response

  Every 8 weeks from time of first dose of study medication until disease progression or death from any cause, assessed up to 300 weeks.

• Determine the impact of Osimertinib plus SABR on the length of time until next therapy needed

  Every 8 Weeks from time of first dose of study medication until subsequent SABR, discontinuation, or disease progression, assessed up to 300 weeks.

• Determine the impact of Osimertinib plus SABR on tumor response

  Every 8 weeks from time of first study medication dose until discontinuation or subject death from any cause, assessed up to 300 weeks.

• Determine the impact of Osimertinib plus SABR on the duration of time while on Osimertinib

  Every 8 weeks from time of first study medication dose until disease progression, discontinuation or subject death from any cause, up to 300 weeks.

Study Arms (1)

Osimertinib

EXPERIMENTAL

Osimertinib in combination with Stereotactic Ablative Radiation (SABR)

Drug: Osimertinib; Radiation: SABR

Interventions

Osimertinib DRUG

Osimertinib 80mg tablet to be taken once daily.

Also known as: AZD9291, TAGRISSO

Osimertinib

SABR RADIATION

Stereotactic Ablative Radiation (SABR)

Osimertinib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Age \> 18 years
• Advanced EGFR exon 19 or 21 mutant NSCLC, not amenable to curative surgery or radiotherapy. EGFR mutations may be demonstrated by standard, clinically accepted methods, including direct gene sequencing, PCR, and NextGen sequencing.
• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Patients must have a life expectancy ≥ 12 weeks.
• Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
• Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
• Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution
• Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
• Male patients should be willing to use barrier contraception.
• 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.
• At least one lesion, not previously irradiated, that can be accurately assessed at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
• Adequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
• Absolute neutrophil count \>1.5 x 109/L
• Platelet count \>100 x 109/L

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site).
• Previous treatment with osimertinib or any EGFR TKI.
• Previous treatment with immunotherapy or any check point inhibitors.
• Treatment with an investigational drug within five half-lives of the compound
• Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 week prior) (Appendix A). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy.
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
• Patients with symptomatic CNS metastases who are neurologically unstable
• Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc using Fredericia's formula) \> 470 msec
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib
• History of hypersensitivity to osimertinib (or drugs with a similar chemical structure or class to osimertinib) or any excipients of these agents

Sponsors & Collaborators

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

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (1)

• Sampath S, Rashdan S, Iyengar P, Mickel TA, Zhang S, Ahn C, Gao A, Dowell JE, Zhang Y, Westover KD, Cole SM, Amini A, Rock A, Massarelli E, Koczywas M, Gerber DE. Osimertinib plus consolidative radiotherapy for advanced EGFR mutant non-small cell lung cancer: a multicentre, single-arm, phase 2 trial. EClinicalMedicine. 2025 Aug 26;87:103435. doi: 10.1016/j.eclinm.2025.103435. eCollection 2025 Sep.

  PMID: 41054436 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Sawsan Rashdan, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

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: Assistant Professor

Study Record Dates

• First Submitted: June 29, 2018
• First Posted: September 12, 2018
• Study Start: September 26, 2018
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: November 4, 2025

Record last verified: 2025-10

Locations

US (2)