Trial Title:
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
NCT ID:
NCT06014827
Condition:
Lung Non-Small Cell Carcinoma
Stage IV Lung Cancer AJCC v8
Conditions: Official terms:
Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Osimertinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (BgRT/SBRT)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT or PET/CT scan
Arm group label:
Treatment (BgRT/SBRT)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Osimertinib
Description:
Given PO
Arm group label:
Treatment (BgRT/SBRT)
Other name:
AZD-9291
Other name:
AZD9291
Other name:
Mereletinib
Other name:
Tagrisso
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT
Arm group label:
Treatment (BgRT/SBRT)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Radiation
Intervention name:
Stereotactic Body Radiation Therapy
Description:
Undergo BgRT/SBRT
Arm group label:
Treatment (BgRT/SBRT)
Other name:
SABR
Other name:
SBRT
Other name:
Stereotactic Ablative Body Radiation Therapy
Intervention type:
Other
Intervention name:
Survey Administration
Description:
Ancillary study
Arm group label:
Treatment (BgRT/SBRT)
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.
Detailed 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.
Criteria for eligibility:
Criteria:
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)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Medical Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Arya Amini
Phone:
626-218-2247
Email:
aamini@coh.org
Investigator:
Last name:
Arya Amini
Email:
Principal Investigator
Facility:
Name:
Yale University
Address:
City:
New Haven
Zip:
06520
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Henry S. Park
Email:
henry.park@yale.edu
Investigator:
Last name:
Henry S. Park
Email:
Principal Investigator
Start date:
October 9, 2024
Completion date:
July 11, 2026
Lead sponsor:
Agency:
City of Hope Medical Center
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
City of Hope Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06014827
