Biologically Guided Radiation Therapy (BgRT) and Stereotactic Body Radiation Therapy (SBRT) With Osimertinib for the Treatment of Patients With Oligoprogressive EGFR Positive Non-small Cell Lung Carcinoma

Stage IV Lung Cancer AJCC v8 Clinical Trial

Official title:

Phase II Trial of the Addition of Biologically Guided Radiation Therapy (BgRT) and Stereotactic Body Radiation Therapy (SBRT) to First Line Osimertinib in Oligoprogressive EGFR Positive Non-Small Cell Lung Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06014827
• Other study ID #: 22624
• Secondary ID: NCI-2023-0604122
• Status: Recruiting
• Phase: Phase 2
• Start date: June 25, 2024
• Est. completion date: July 11, 2026

Study information

• Verified date: February 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial tests how well biologically guided radiation therapy (BgRT) and stereotactic body radiation therapy (SBRT) with osimertinib works for the treatment of EGFR positive non-small cell lung carcinoma that has spread from where it first started (primary site) to a limited number of anatomic sites (oligoprogressive). BgRT is radiation that uses specialized imaging to during treatment to target the active tumor and direct radiation to tumors in order to kill and shrink tumor cells. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Osimertinib is in a class of medications called kinase inhibitors. It works by blocking the action of a protein called EGFR that signals cancer cells to multiply. This helps slow or stop the spread of tumor cells. Giving BgRT with SBRT and osimertinib may kill more tumor cells in patients with oligoprogressive EGFR positive non-small cell lung carcinoma.

Description:

PRIMARY OBJECTIVE: I. To estimate the percent of patients receiving benefit at 6 months from the addition of BgRT/SBRT to first line osimertinib in EGFR positive non-small cell lung cancer (NSCLC) patients with oligoprogressive disease (disease control rate [DCR]). SECONDARY OBJECTIVES: I. To evaluate the tolerability of adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. II. To estimate the overall survival when adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. III. To describe the effect on quality of life (QOL) when adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. IV. To describe the effect on quantified fludeoxyglucose F-18 (FDG) uptake changes when adding BgRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. V. To estimate local and distant control rates when adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. VI. To estimate the extracranial progression free survival (PFS) when adding SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. VII. To estimate the time to treatment failure (TTF) when adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. VII. To estimate percentage of patients needing salvage BgRT/SBRT when adding SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. EXPLORATORY OBJECTIVES: I. To identify potential predictors of outcome when adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. II. To describe the changes in circulating tumor deoxyribonucleic acid (ctDNA) levels when adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. OUTLINE: Patients continue to receive osimertinib orally (PO) daily (QD) in the absence of unacceptable toxicity. Patients undergo BgRT/SBRT every other day for 5 treatments. Patients then continue to receive osimertinib and are monitored via imaging. If additional progression is found, patients may receive additional BgRT/SBRT therapy. Treatment continues in the absence of > 5 sites of progression, unacceptable toxicity, or the stopping of osimertinib for more than 4 weeks. Patients undergo computed tomography (CT) scan or positron emission tomography(PET)/CT scan and blood sample collection throughout the study. After completion of initial radiation therapy, patients follow up at 1 week, 3 months, 6 months and 12 months and then for an additional year.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: July 11, 2026
• Est. primary completion date: July 11, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Age: >= 18 years
• Eastern Cooperative Oncology Group (ECOG) =< 2
• Histologically confirmed advanced non-small cell lung cancer (NSCLC)
• The tumor harbors 1 of the 2 common epidermal growth factor receptor (EGFR) mutations known to be associated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) sensitivity (Ex19del or L858R), either alone or in combination with other epidermal growth factor receptor (EGFR) mutations, which may include T790M.
• Disease progression in the metastatic setting on PET or CT imaging when receiving first line standard/approved single agent osimertinib after having had stable disease (per Response Evaluation Criteria in Solid Tumors [RECIST] version [v] 1.1 or PET Response Criteria in Solid Tumors [PERCIST] v 1.0) for more than 6 months
• Disease progression must be in the form of 1-5 extracranial sites (any number of metastatic sites at initial diagnosis will qualify). For progression of the primary and oligoprogressive site(s), the primary should be treated with curative/local control intent. The primary, if progressing is considered as 1 site. Maximum of 3 lesions per organ (i.e. patient with 4 oligoprogressive sites in the lung would be excluded). Each lesion will be considered as 1 "site" so 3 lesions in the lung for example will be considered 3 sites. Patients with prior metastases that have been treated with ablative therapies before their current line of systemic therapy are eligible. Patients with brain metastases can be included but brain metastases must be treated (asymptomatic and have had no requirement for steroid medication for 1 week prior to the first dose of study drug and have completed radiation 2 weeks prior to the first dose of study drug) prior to enrollment (brain metastases [mets] will not be counted as a site of progression)
• Lesion(s) must be amenable to SBRT as determined by the radiation oncologist. If a patient is unable to receive a minimum of 30 Gy in 5 fractions they will not qualify
• At least one lesion must be amenable to BgRT which includes either a lung or bone metastasis, greater than or equal to 2 cm, which can also receive a minimum of 30 Gy in 5 fractions
• No prior systemic therapy for advanced disease other than osimertinib
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 4 months after the last dose of protocol therapy
• Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
• Patients must be able to swallow and retain oral medications
• Life expectancy of at least 6 months

Exclusion Criteria:

• Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy (6 weeks for nitrosoureas or mitomycin C). Exceptions to this exclusion are brain radiation (2 weeks) and osimertinib
• Strong CYP3A4 inducers/ inhibitors within 14 days prior to day 1 of protocol therapy
• Patients receiving class 1A or class III antiarrhythmic agents within 14 days prior to day 1 of protocol therapy
• Drugs known to prolong the corrected QT (QTc) interval
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• Clinically significant uncontrolled illness
• Active infection requiring antibiotics bacterial, viral, or fungal infections, requiring systemic therapy
• Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
• Prior malignancy other than carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated 5 or more years prior to study entry with no subsequent evidence of recurrence. Patients with a history of low grade (Gleason score =< 6 =Gleason group 1) localized prostate cancer will be eligible even if diagnosed less than 5 years prior to study entry. Other malignancies with low probability of recurrence may be allowed with primary investigator (PI) approval
• Females only: Pregnant or breastfeeding
• Any malabsorption condition
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Diagnosis of congenital long QT syndrome
• New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG)
• Clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroid medication for 1 week prior to the first dose of study drug and have completed radiation 2 weeks prior to the first dose of study drug
• Patients with active interstitial lung disease (ILD) / pneumonitis or with a history of ILD/ pneumonitis requiring steroids
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Lung Non-Small Cell Carcinoma
• Stage IV Lung Cancer AJCC v8

Intervention

Procedure:
• Biospecimen Collection
Undergo blood sample collection
• Computed Tomography
Undergo CT or PET/CT scan

Drug:
• Osimertinib
Given PO

Procedure:
• Positron Emission Tomography
Undergo PET/CT

Radiation:
• Stereotactic Body Radiation Therapy
Undergo BgRT/SBRT

Other:
• Survey Administration
Ancillary study

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California
United States	Yale University	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of patients on planned protocol treatment	Patient counts and percentages will be provided.	At 6 months
Secondary	Rate of all grades and grade >= 3 adverse events at least possibly related to study therapy	As measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Observed toxicities will be summarized, for all patients in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.	Up to 2 years
Secondary	Overall survival	Will be estimated using the product-limit method of Kaplan-Meier. Two-sided 95% confidence intervals will be computed.	From the date of study enrollment to the date of death from any cause, up to 2 years
Secondary	Change in quality of life (QOL)	As measured by Functional Assessment of Cancer Therapy-General (FACT-G) v4. Repeated QOL assessments will be tabulated and graphically displayed to describe the changes of QOL outcomes over time.	From baseline to 3 months post initial stereotactic body radiation therapy (SBRT)
Secondary	Change in fludeoxyglucose (FDG) uptake	As measured by metabolic tumor volume and total lesion glycolysis at each fraction. Will be analyzed using independent student's t-test to compare normal variables and non-parametric tests including Wilcoxon's signed-rank test for paired data will be used to compare non-normally distributed variables. Repeated measures analysis of variance (ANOVA) will be used to test for differences at more than one time point. Correlation between metabolic tumor volume, total lesion glycolysis and circulating tumor deoxyribonucleic acid (ctDNA) and time to treatment failure (as described above) as well as overall survival will be explored using univariate and multivariate Cox regression.	From baseline to completion of SBRT, up to 2 years
Secondary	Ratio of patients achieving local control and distant control		Up to 2 years
Secondary	First occurrence of disease progression	By Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) v1.0 or Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. A progressive event will occur when: more than five sites of progression based on PERCIST or RECIST, inability to receive more biologically guided radiation therapy (BgRT)/SBRT or osimertinib, physician decision to come off study or change therapy, patient withdrawal of consent or death will all be considered events. Will be estimated using the product-limit method of Kaplan-Meier.	From study entry to first occurrence of disease progression, up to 2 years
Secondary	Time to treatment failure	Will be estimated using the product-limit method of Kaplan-Meier. For time to treatment failure, a progressive event will occur when: more than five sites of progression based on PERCIST or RECIST, inability to receive more BgRT/SBRT or osimertinib, physician decision to come off study or change therapy, patient withdrawal of consent or death will all be considered events.	From study entry to treatment failure, up to 2 years
Secondary	Ratio of patients needing salvage BgRT/SBRT		Up to 1 year