| Eligibility |
Participant Inclusion Criteria (both Part I and Part II)
Monitoring Phase
- Stage IV NSCLC. Note that patients are eligible for the study if they have received
definitive treatment for early stage disease, presuming that they remain candidates
for local ablative therapy (LAT).
- AJCC 8th Edition Stage IV disease
- Has had up to four cycles of standard first-line systemic therapy +/- 3 weeks, defined
as: a) platinum-doublet chemotherapy, b) ICI, or c) platinum-doublet chemotherapy +
ICI at the baseline ctDNA draw being used for the study.
- Patient initiated their ctDNA blood draws during their first 4 cycles of first line
systemic therapy +/- 3 weeks (during their first 4 cycles, or up to 3 weeks
before/after they have begun/ended their first 4 cycles of systemic therapy
- Ten or less metastatic lesions (Note that this criterion includes lesions, not sites:
3 brain metastases = 3 lesions).
° Imaging defining extent of disease should be performed within 4 weeks of ctDNA blood
draw
1. PET/CT scan or CT scan of the chest/abdomen/pelvis within 4 weeks of blood draw
for ctDNA analysis
2. MRI or CT scan of the brain at baseline, AND within 4 weeks of blood draw for
ctDNA analysis (optional, per discretion of treating physician)
- All lesions amenable to LAT.
o Note that patients who receive local therapy (radiation, surgery, or RFA) prior to
enrollment for palliative purposes or to CNS lesions are eligible for enrollment if:
a) all other eligibility criteria are met and b) at least one other lesion is amenable
to LAT and is RECIST evaluable. All lesions treated for palliative purposes will also
be counted towards the total number of lesions.
- At least one site of measurable disease
- ECOG Performance status 0 - 2.
- Age = 18 years.
- The participant, or their legally authorized representative (LAR) are able to provide
informed consent.
- Adequate baseline organ function to allow SBRT to all relevant targets, as determined
by the treating radiation oncologist based on lesion location, lesion size, and
proximity to relevant organs at risk.
Therapeutic Phase - Being Enrolled from Monitoring Phase
- Has received at least 2 cycles of treatment, remains on first-line therapy
- No evidence of radiographic RECIST 1.1* progression (as defined above), as measured
through the following imaging modalities:
- 1) PET/CT scan or CT scan of the chest/abdomen/pelvis within 4 weeks of blood
draw for ctDNA analysis
- 2) MRI or CT scan of the brain at baseline, AND within 4 weeks of blood draw for
ctDNA analysis (optional, per discretion of treating physician)
- NR-VAF results within 4 weeks of enrollment
- All active lesions amenable to LAT
° Note that patients who receive local therapy (radiation, surgery, or RFA) prior to
enrollment for palliative purposes or to CNS lesions are eligible for enrollment if:
a) all other eligibility criteria are met and b) at least one other lesion is amenable
to LAT and is RECIST evaluable. All lesions treated for palliative purposes will also
be counted towards the total number of lesions. Female subjects must either be of
non-reproductive potential (i.e. post-menopausal by history: >/= 60 years old and no
menses for 1> year without an alternative medical cause; OR history of hysterectomy,
OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must
have a negative pregnancy test (serum) within 2 weeks or a urine pregnancy test the
day of treatment
- Note that patients can either be: a) enrolled on the Monitoring Phase, followed by the
Therapeutic Phase, or b) enrolled directly on to the Therapeutic Phase if they present
for enrollment at the time that the therapeutic phase would be delivered and
retrospectively would have met all of the criteria of the monitoring phase.
- Example: If a patient has received 2 cycles of systemic therapy and has NR-VAF,
then presents to the clinic for enrollment, they can be enrolled on to the
Therapeutic Phase if they meet all of the criteria in the Therapeutic Phase and
upon evaluating their prior ctDNA/imaging results would have also met the
criteria for the Monitoring Phase.
- This allowance will substantially increase accrual, as many patients will present
after undergoing baseline ctDNA analysis, and does not affect the scientific
question that the study addresses.
Therapeutic Phase - Being Enrolled Directly into Therapeutic Phase
As the criteria below indicate, patients can either be: a) enrolled on the Monitoring
Phase, followed by the Therapeutic Phase, or b) enrolled directly on to the Therapeutic
Phase if they present for enrollment at the time that the therapeutic phase would be
delivered and retrospectively would have met all of the criteria of the monitoring phase.
For example, if a patient has received 2 cycles of systemic therapy and has NR-VAF, then
presents to the clinic for enrollment, they can be enrolled on to the Therapeutic Phase if
they meet all of the criteria in the Therapeutic Phase and upon evaluating their prior
ctDNA/imaging results would have also met the criteria for the Monitoring Phase. This
allowance will substantially increase accrual, as many patients will present after
undergoing baseline ctDNA analysis, and does not affect the scientific question that the
study addresses.
Inclusion Criteria for Patients Being Enrolled Directly into the Therapeutic Phase
- Stage IV NSCLC. Note that patients are eligible for the study if, prior to the
development of stage IV disease, they have received definitive treatment for early
stage disease, presuming that they remain candidates for local ablative therapy (LAT).
- AJCC 8th Edition Stage IV disease
- Ten or less metastatic lesions (Note that this criterion includes lesions, not sites:
3 brain metastases = 3 lesions).
o Imaging defining extent of disease should be performed within 4 weeks of ctDNA blood
draw
- All lesions amenable to LAT.
- At least one site of measurable disease
- Detectable ctDNA
- ECOG Performance status 0 - 2.
- Age = 18 years.
- The participant, or their legally authorized representative (LAR) are able to provide
informed consent.
- Female subjects must either be of non-reproductive potential (i.e. post-menopausal by
history: >/= 60 years old and no menses for 1> year without an alternative medical
cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history
of bilateral oophorectomy) or must have a negative pregnancy test (serum) within 2
weeks or a urine pregnancy test the day of treatment.
- Adequate baseline organ function to allow SBRT to all relevant targets, as determined
by the treating radiation oncologist based on lesion location, lesion size, and
proximity to relevant organs at risk.
- Patient initiated their ctDNA blood draws during their first 4 cycles of first line
systemic therapy +/- 3 weeks (during their first 4 cycles, or up to 3 weeks
before/after they have begun/ended their first 4 cycles of systemic therapy.
- Has received at least 2 cycles of treatment, remains on first-line therapy
- No evidence of radiographic RECIST 1.1* progression (as defined above), as measured
through the following imaging modalities:
- 1) PET/CT scan or CT scan of the chest/abdomen/pelvis within 4 weeks of blood
draw for ctDNA analysis
- 2) MRI or CT scan of the brain at baseline, AND within 4 weeks of blood draw for
ctDNA analysis (optional, per discretion of treating physician)
- NR-VAF results within 4 weeks of enrollment
o For patients that do not have detectable ctDNA at enrollment in the monitoring
phase, NR-VAF is defined as the emergence of detectable VAF on follow up blood draws
- All active lesions amenable to LAT o Note that patients who receive local therapy
(radiation, surgery, or RFA) prior to enrollment for palliative purposes or to CNS
lesions are eligible for enrollment if: a) all other eligibility criteria are met and
b) at least one other lesion is amenable to LAT and is RECIST evaluable. All lesions
treated for palliative purposes will also be counted towards the total number of
lesions.
Exclusion Criteria:
- At the time of therapeutic phase enrollment, complete response radiographically (no
lesions to target)
- Patients with CNS-only disease (due to limited capacity of peripheral blood ctDNA to
detect CNS lesions)
- Planned treatment by targeted agents (e.g. tyrosine kinase inhibitors) or patient not
a candidate for systemic therapy
- Serious medical co-morbidities precluding radiotherapy or ablation, determined at the
discretion of the treating investigator.
- At the time of therapeutic phase enrollment, pregnant or lactating women.
- Physical limitation to undergo stereotactic radiotherapy.
- Other active malignancy within the last year except for basal cell carcinoma of the
skin and in situ malignancy even if without evidence of disease.
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