Non Small Cell Lung CancerPhase 2NCT04485026
Local Consolidative Radiotherapy for Oligoprogressive in Non-small Cell Lung Carcinoma
A Phase 2 study testing Local consolidative radiation therapy in people with Non Small Cell Lung Cancer and Oligoprogressive, run by Wake Forest University Health Sciences.
Trial summary
This is a randomized phase II study designed to evaluate the effect of local consolidative radiation therapy (LCT) to all sites of oligoprogressive disease in patients with metastatic non-small cell lung carcinoma who have progressed through first line systemic therapy containing an immune checkpoint inhibitor (ICI). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer, Oligoprogressive
- What is being tested?
- Local consolidative radiation therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 4 Nov 2020to 9 May 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of non-small cell lung cancer.
- Have completed at least 4 cycles of a first line systemic therapy regimen for metastatic disease that includes a PD-1 axis targeted agent prior to progression. (Patients may be on maintenance/consolidation anti PD-1 axis therapy or have completed maintenance anti PD-1 axis therapy within the last 3 months at the time of progression).
- Initial response of stable disease (SD), partial response (PR) or complete response (CR) in at least one lesion prior to progression as defined by RECIST v1.1 criteria.
- Oligoprogressive disease in 4 or fewer lesions (Progression of the primary tumor and/or regional lymph nodes will be counted as one lesion)
- CNS lesions will not count towards the 4 or fewer progressive lesions if they are all able to be treated with stereotactic radiosurgery.
- Progression by RECIST v1.1 criteria or by PET/CT criteria will be considered progressive disease. Both are not required to determine progressive disease.
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- Progression for study entry will be defined as by a modified RECIST v1.1 criteria, including: Development of a new lesion; increase in the longest diameter (shortest diameter for lymph node lesions) of any individual lesion by 20% above nadir and a minimal increase of 5 mm.
- In cases of PET/CT, the criteria for progression of PET/CT are: Any individual FDG avid lesion with an uptake greater than twice that of the surrounding tissue on the attenuation corrected image. Any individual FDG avid lesion with greater than 30% increase in 18F-FDG SUV peak, with greater than 0.8 SUV units increase in tumor SUV from the nadir or the pre-enrollment PET/CT in pattern typical of tumor and not of infection/treatment effect per the treating investigator. Visible increase in the extent of 18F-FDG uptake of any lesion by 20% in the longest diameter and an absolute increase of at least 5mm that is not consistent with treatment effect and/or infection per the treating investigator. No more than the following number of progressing lesions in any one organ (including any lesions previously treated with radiation therapy). Less than or equal to four (4) lung lesions (including primary and mediastinal lymph nodes as one lesion). Less than or equal to three (3) liver lesions. Less than or equal to three (3) cumulative vertebral lesions
- At least one non-progressing lesion, which may not have undergone prior definitive local therapy.
- All progressive lesions must be amenable to definitive radiation therapy as determined by the treating radiation oncologist.
- Age of 18 years or greater.
- ECOG Performance Status of 0-2.
- Negative serum or urine pregnancy test within 2 weeks of the date of enrollment
- for women of child-bearing potential.
- Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative).
- If EGFR and/or ALK status is unknown, the patient is eligible.
Who cannot join
- Inability to safely treat all progressive lesions with definitive radiation therapy as determined by the treating radiation oncologist
- Patients may not be receiving any other investigational anti-cancer agents.
- Progressive disease in the CNS only.
- Known targetable EGFR mutation or EML4-ALK fusion.
- Progressive cutaneous metastases.
- Progressive disease involving the esophagus, stomach, or intestines.
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- Malignant pleural or pericardial effusion at the time of oligoprogression.
- Thoracentesis/thoracoscopic biopsy for a stable or asymptomatic pleural effusion is not required unless the effusion is hypermetabolic on PET/CT or if there are active pleural based metastatic lesions at the time of oligoprogression.
- Effusions that are too small for thoracentesis/pericardiocentesis are considered resolved for the purposes of trial eligibility.
- Pregnant women are excluded from this study because radiation therapy has known potential for teratogenic or abortifacient effects.
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements as determined by the treating physician.
About this study
Official title: A Randomized Phase II Study of Local Consolidative Radiotherapy Versus Standard of Care Second Line Systemic Therapy in Patients With Oligoprogressive NSCLC on Immune Checkpoint Inhibitors
This is a randomized phase II study designed to evaluate the effect of local consolidative radiation therapy (LCT) to all sites of oligoprogressive disease in patients with metastatic non-small cell lung carcinoma who have progressed through first line systemic therapy containing an immune checkpoint inhibitor (ICI).
Read the detailed description
Primary Objective: To compare overall survival (OS) from the time of the time of randomization between the treatment and control groups.
Secondary Objective(s)
- To compare the extra-CNS PFS2 (EC-PFS2), defined as the time to extracranial disease progression on second line systemic therapy or death from the first day of local consolidative radiation therapy (treatment group) or from the start of second line therapy (control group).
- To evaluate time to initiation of second line systemic therapy or palliative care after completion of local consolidative therapy in the treatment group
- To compare the toxicities in the treatment and control groups;
- To compare overall progression free survival from the time of the first day of local consolidative radiation therapy for the treatment group and from the start of second line therapy for the control group
- To compare the pattern of next progression on second line therapy in the treatment group vs the control group.
- To evaluate local progression in lesions treated with local consolidative radiation therapy.
- Conditions
- Non Small Cell Lung Cancer, Oligoprogressive
- Being tested
- Local consolidative radiation therapy, Standard of care radiation therapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Local consolidative radiation therapyRadiation
All local consolidative radiation therapy should be delivered using hypofractionated local consolidative radiation therapy (>2 Gy per fraction). Exceptions may be approved on a case by case basis by the trial principal investigator. Three-dimensional conformal radiotherapy (3D-CRT), intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), stereotactic body radiotherapy (SBRT), stereotactic radiosurgery (SRS), and proton beam therapy (PBT) are all acceptable.
Standard of care radiation therapyDrug
Standard of care palliative radiotherapy to symptomatic lesions is permissible. The dose to symptomatic lesions should not exceed 30 Gy in 10 fractions. Brain metastases will be treated with standard of care CNS therapy throughout the study. This may include (but is not limited to) stereotactic radiosurgery, neurosurgical intervention, whole brain radiotherapy
| Study group | Role | What they receive |
|---|---|---|
| Local Consolidative Radiation Therapy Arm | Experimental | Definitive external beam radiation therapy will be delivered to all sites of progressive disease for all patients. The technique used to deliver radiation therapy will be determined by the treating radiation oncologist. Receives: Radiation: Local consolidative radiation therapy |
| Standard of Care - Control Arm | Active comparator | Second line systemic therapy is at the discretion of the treating medical oncologist. Receives: Drug: Standard of care radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
In each arm overall survival will be defined as the time from randomization to death from any cause. . Patients who are alive at the last follow up at the end of the study will be censored at the date of the last follow up appointment. A comparison of overall survival between the two groups will be made first using bivariate Kaplan-Meier method and then a multivariable Cox proportional hazards model. Participants who do not die during the course of observation will be right censored. Key covariates to be included in multivariable modeling include age, ECOG status, number of progressive treated sites (1 vs 2-4), and PD-L1 status (>=50%; 1%-49%; < 1%).
Measured: 3 years
Secondary outcomes (6)
Time to Progression Between Both Arms
Investigators will compare progression after second line of therapy between both arms first using the bivariate Kaplan-Meier method and then a multivariable Cox proportional hazards model age, ECOG status, number of progressive treated sites (1 vs 2-4), and PD-L1 status (>=50%; 1%-49%; < 1%). RECIST version 1.1 criteria will be used to assess for progression.
Measured: 3 years
Time to Second Line of Systemic Therapy or Palliative Care (Local Consolidative Radiation Therapy Arm Only)
The time to the second line systemic therapy or palliative care will be defined as the time from the completion of local consolidation therapy to the first day of cycle 1 of a systemic therapy the patient has not yet received OR the date of hospice enrollment, whichever is sooner. Patients experiencing neither of these events will be censored at last follow up visit. Estimated median time to second line therapy (or palliative care) and corresponding 95% confidence interval as well as estimated proportion (and corresponding 95% confidence interval) of the treatment group who have started second-line therapy (or palliative care) by key time points including 6 months, 1 year, and 2 years after the end of local consolidative therapy.
Measured: Up to 2 years after the completion of intervention
Incidences of Toxicities
Toxicities will be evaluated per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Toxicities between the two arms by comparing the proportions with grade 2 or higher, and grade 3 or higher, toxicities of any type at 3, 6, 12, 24 and 36 months following randomization using a chi-square test on the relevant 2x2 contingency table.
Measured: Up to 3 years
Progression Free Survival
Progression free survival will be assessed by a modified RECIST version 1.1 criteria. If any individual target lesion meets RECIST v1.1 criteria - specifically an increase in the longest diameter (shortest diameter for lymph node lesions) of at least 20% and 5 mm absolute increase, the patient will be considered to have progression of disease. The criteria for determining pseudoprogression versus true progression and for mild progression while systemic therapy is held for the delivery of local consolidative radiation therapy in the treatment arm will be used for this outcome measure as well. Repeat oligoprogression will also be counted as progressive disease.
Measured: Up to 5 years
Time to Next Progression Following Local Consolidative Radiation Therapy or Second Line Systemic Therapy
The pattern of next progression following local consolidation therapy (in treatment group) or second line systemic therapy (in control group) into one of three possible mutually exclusive and exhaustive categories: No progression, repeat oligoprogression or polyprogression, and will compare these patterns between the two groups using a chi-square analysis on the resulting 2x3 contingency table.
Measured: Up to 3 years
Proportion of Local of Lesions Treated with Local Consolidative Radiation Therapy That Progress
Investigators will estimate proportion of lesions treated with local consolidative radiation therapy that experienced local progression (yes/no by study end) and construct a 95% confidence interval around this estimate.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2020
- Study start4 Nov 2020
- Primary completion9 May 2024
- Study completion9 May 2024
Why it stopped: No enrollments, low patient population as well as a dramatic change in the insurance approval processes for oligoprogressive state with eviCore saying they do not support SBRT in this setting at all.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Michael Farris, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04485026
- Sponsor's protocol ID
- IRB00068259
- Other IDs
- P30CA012197, WFBCCC62420
- Status last verified
- Apr 2025
- First submitted
- 20 Jul 2020
- Last updated
- 17 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study of Local Consolidative Radiotherapy Versus Standard of Care Second Line Systemic Therapy in Patients With Oligoprogressive NSCLC on Immune Checkpoint Inhibitors
- ClinicalTrials.gov ID
- NCT04485026
- Acronym / sponsor ID
- IRB00068259
- Conditions
- Non Small Cell Lung Cancer, Oligoprogressive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No enrollments, low patient population as well as a dramatic change in the insurance approval processes for oligoprogressive state with eviCore saying they do not support SBRT in this setting at all.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 4 Nov 2020 (actual)
- Primary completion
- 9 May 2024 (actual)
- Study completion
- 9 May 2024 (actual)
- First posted
- 24 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized phase II study designed to evaluate the effect of local consolidative radiation therapy (LCT) to all sites of oligoprogressive disease in patients with metastatic non-small cell lung carcinoma who have progressed through first line systemic therapy containing an immune checkpoint inhibitor (ICI).
Detailed description
Primary Objective: To compare overall survival (OS) from the time of the time of randomization between the treatment and control groups.
Secondary Objective(s)
- To compare the extra-CNS PFS2 (EC-PFS2), defined as the time to extracranial disease progression on second line systemic therapy or death from the first day of local consolidative radiation therapy (treatment group) or from the start of second line therapy (control group).
- To evaluate time to initiation of second line systemic therapy or palliative care after completion of local consolidative therapy in the treatment group
- To compare the toxicities in the treatment and control groups;
- To compare overall progression free survival from the time of the first day of local consolidative radiation therapy for the treatment group and from the start of second line therapy for the control group
- To compare the pattern of next progression on second line therapy in the treatment group vs the control group.
- To evaluate local progression in lesions treated with local consolidative radiation therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Local Consolidative Radiation Therapy Arm | Experimental | Radiation: Local consolidative radiation therapyDefinitive external beam radiation therapy will be delivered to all sites of progressive disease for all patients. The technique used to deliver radiation therapy will be determined by the treating radiation oncologist. |
| Standard of Care - Control Arm | Active comparator | Drug: Standard of care radiation therapySecond line systemic therapy is at the discretion of the treating medical oncologist. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histologically confirmed diagnosis of non-small cell lung cancer.
- Have completed at least 4 cycles of a first line systemic therapy regimen for metastatic disease that includes a PD-1 axis targeted agent prior to progression. (Patients may be on maintenance/consolidation anti PD-1 axis therapy or have completed maintenance anti PD-1 axis therapy within the last 3 months at the time of progression).
- Initial response of stable disease (SD), partial response (PR) or complete response (CR) in at least one lesion prior to progression as defined by RECIST v1.1 criteria.
- Oligoprogressive disease in 4 or fewer lesions (Progression of the primary tumor and/or regional lymph nodes will be counted as one lesion)
- CNS lesions will not count towards the 4 or fewer progressive lesions if they are all able to be treated with stereotactic radiosurgery.
Key exclusion criteria (11 listed)
- Inability to safely treat all progressive lesions with definitive radiation therapy as determined by the treating radiation oncologist
- Patients may not be receiving any other investigational anti-cancer agents.
- Progressive disease in the CNS only.
- Known targetable EGFR mutation or EML4-ALK fusion.
- Progressive cutaneous metastases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Local consolidative radiation therapyAll local consolidative radiation therapy should be delivered using hypofractionated local consolidative radiation therapy (>2 Gy per fraction). Exceptions may be approved on a case by case basis by the trial principal investigator. Three-dimensional conformal radiotherapy (3D-CRT), intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), stereotactic body radiotherapy (SBRT), stereotactic radiosurgery (SRS), and proton beam therapy (PBT) are all acceptable. | Radiation | Local Consolidative Radiation Therapy Arm |
| Standard of care radiation therapyStandard of care palliative radiotherapy to symptomatic lesions is permissible. The dose to symptomatic lesions should not exceed 30 Gy in 10 fractions. Brain metastases will be treated with standard of care CNS therapy throughout the study. This may include (but is not limited to) stereotactic radiosurgery, neurosurgical intervention, whole brain radiotherapy | Drug | Standard of Care - Control Arm |
Primary outcome
Overall Survival
Time frame: 3 years
In each arm overall survival will be defined as the time from randomization to death from any cause. . Patients who are alive at the last follow up at the end of the study will be censored at the date of the last follow up appointment. A comparison of overall survival between the two groups will be made first using bivariate Kaplan-Meier method and then a multivariable Cox proportional hazards model. Participants who do not die during the course of observation will be right censored. Key covariates to be included in multivariable modeling include age, ECOG status, number of progressive treated sites (1 vs 2-4), and PD-L1 status (>=50%; 1%-49%; < 1%).
6 secondary outcomes
Time to Progression Between Both Arms
Time frame: 3 years
Time to Second Line of Systemic Therapy or Palliative Care (Local Consolidative Radiation Therapy Arm Only)
Time frame: Up to 2 years after the completion of intervention
Incidences of Toxicities
Time frame: Up to 3 years
Progression Free Survival
Time frame: Up to 5 years
Time to Next Progression Following Local Consolidative Radiation Therapy or Second Line Systemic Therapy
Time frame: Up to 3 years
Proportion of Local of Lesions Treated with Local Consolidative Radiation Therapy That Progress
Time frame: Up to 5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Farris, MD principal investigator
Wake Forest University Health Sciences
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Local consolidative radiation therapy in people with Non Small Cell Lung Cancer and Oligoprogressive, run by Wake Forest University Health Sciences.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2025.