Metastatic Nonsmall Cell Lung CancerPhase 2I-SABRNCT03825510
Immunotherapy SBRT Sensitization of the Programmed Death-1 (PD-1) Effect
A Phase 2 study testing Stereotactic Body Radiotherapy in people with Metastatic Nonsmall Cell Lung Cancer and Non Small Cell Lung Cancer, run by Crozer-Keystone Health System at 1 site in United States.
Trial summary
The purpose of this study is to determine efficacy, safety of Stereotactic Body Radiotherapy (SBRT) in combination with immunotherapy in participants with metastatic non-small cell lung cancer (NSCLC) who are eligible for an immunotherapy agent. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Nonsmall Cell Lung Cancer, Non Small Cell Lung Cancer
- What is being tested?
- Stereotactic Body Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Apr 2017to 8 Mar 2022
- 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 or cytologically confirmed Stage IV NSCLC according to the 7th AJCC staging manual.
- Eligible for an immunotherapy agent. Patients who progress after drug therapy (3 months) for ALK, EGFR or ROS mutation positive lung cancer are eligible.
- At least 2 lesions that are safely amenable to SBRT. ECOG <=2.
- At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for response assessment or at least 1 lesion with FDG avidity and CT correlate that can be monitored for PET-CT response by SUV Max increase or decrease.
- Normal Hepatic and renal function.
- Bone marrow reserve:
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- ANC ≥ 1.5 x 109/L
- Hemoglobin ≥9.0 g/dL
- Platelet count ≥75 x 109/L
- Ability to comply with follow-up visits and evaluations, treatment planning and studies and other study related procedures and visits.
- Ability to sign informed consent.
Who cannot join
- Patients with active CNS metastases
- Active, known or suspected auto-immune disease.
- Patients with medical conditions that require systemic immunosuppression.
- Patients with a history of interstitial lung disease.
- Prior treatment with immune checkpoint inhibitors/immonotherapy.
- Other active malignancy requiring intervention.
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- Prior lung radiation, with the only metastatic targets in the lungs.
- Unresolved toxicity from prior chemotherapy or anti-cancer treatment.
- Current or prior enrollment in clinical trial with an investigational drug within 4 weeks.
- Pregnancy or positive pregnancy test.
Trial locations and contacts
1 site in 1 country.
United States1 site
Philadelphia CyberKnife
Philadelphia, Pennsylvania, 19083
About this study
Official title: A Prospective Trail of Immunotherapy and Stereotactic Body Radiotherapy (SBRT) for the Treatment of Metastatic Lung Cancer: SBRT Sensitization of the Programmed Death-1 (PD-1) Effect
The purpose of this study is to determine efficacy, safety of Stereotactic Body Radiotherapy (SBRT) in combination with immunotherapy in participants with metastatic non-small cell lung cancer (NSCLC) who are eligible for an immunotherapy agent.
Read the detailed description
Blockade of the PD-1/PD-L1 T-cell checkpoint pathway is an effective and well tolerated approach to stimulating the immune response which is a critical option in the treatment of metastatic NSCLC. However, progression free survival (PFS) is increased by only 2-4 months and median overall survival (OS) by 3-9 months.
There is compelling evidence that PFS is increased up to 3 fold and OS by 2 fold in patients receiving a course of radiation therapy while on immunotherapy. Radiotherapy is known to induce immunogenic tumor cell death and upregulation of dendritic cells and antigen presentation leading to activation of cytotoxic T-Cells. Dramatic T-cell activation has been demonstrated where tumor regression occurs outside the radiation treatment field in a phenomenon termed the abscopal effect and is associated with high dose radiation delivered via SBRT.
As such, SBRT activation of T-cells could be complementary to immunotherapy and enhance T-cell mediated killing via PD-L1 blockade which could lead to lasting and durable tumor response with improved progression free survival and overall survival.
- Being tested
- Stereotactic Body Radiotherapy
- Keywords
- Opdivo, Keytruda, Cyberknife
- 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.
Stereotactic Body RadiotherapyRadiation
Also called SBRT, SRS, SABR, CyberKnife
All patients in this trial will be treated with fractionated Stereotactic body radiation therapy.
SBRT will be delivered to <=3 sites in 3-5 fractions followed by administration of the specified immunotherapy agent (Nivolumab or Pembrolizumab). This approach will take advantage of the transient increase in antigen availability, increased antigen presentation and upregulation of PD-1 by tumor cells following ablative radiation therapy.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Not described Receives: Radiation: Stereotactic Body Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Determine overall survival in patients receiving SBRT and immunotherapy as compared to landmark trials of patients receiving immunotherapy alone (Checkmate 057, Keynote 024)
Measured: 24 months
Acute Toxicity: Radiation pnuemonitis measured using NCI CTCAE version 4.0
Determine excess/unexpected toxicity that cannot be attributed to routine radiation therapy or immunotherapy side effects.
Measured: 0-15 weeks
Secondary outcomes (4)
Progression Free Survival
- To determine the progression free survival measured from time of enrollment to first evidence of progressive disease and evaluated 3 months after treatment initiation
Measured: 3-24 Months
Local Control
To determine the local control measured from time of enrollment to first evidence of progressive disease at the treatment site
Measured: 0-24 Months
Late Toxicity: Pulmonary, Bone or Visceral organ toxicity evaluated 6 months from completion of treatment using NCI CTCAE version 4.
the incidence of grade ≥ 3 , pneumonitis 6 months after completing SBRT the incidence of any grade pulmonary fibrosis 6 months after completing SBRT the incidence of grade ≥ 3 , bone fracture 6 months after completing SBRT the incidence of grade ≥ 3 visceral organ toxicity at or near a treated site (e.g colitis, nephritis, hepatitis) 6 months after completing SBRT
Measured: 6-24 Months
Impact of Tumor Burden
To determine the influence of number of metastatic sites on OS, and PFS. Patients will be stratified based on number of metastatic sites <=3, 4-5, >5
Measured: 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2019
- Study start28 Apr 2017
- Primary completion8 Mar 2022
- Study completion8 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Nonsmall Cell Lung CancerStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Crozer-Keystone Health System
- Sponsor type
- University, hospital or other
- Collaborators
- Saint Peters University Hospital, Community Medical Center, Toms River, NJ
- Responsible party
- Principal investigator, Rachelle Lanciano M.D., Crozer-Keystone Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03825510
- Sponsor's protocol ID
- CKHS 17-009
- Acronym
- I-SABR
- Status last verified
- Mar 2023
- First submitted
- 18 Aug 2017
- Last updated
- 6 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Trail of Immunotherapy and Stereotactic Body Radiotherapy (SBRT) for the Treatment of Metastatic Lung Cancer: SBRT Sensitization of the Programmed Death-1 (PD-1) Effect
- ClinicalTrials.gov ID
- NCT03825510
- Acronym / sponsor ID
- I-SABR / CKHS 17-009
- Keywords
- Opdivo, Keytruda, Cyberknife
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Crozer-Keystone Health SystemUniversity, hospital or other
- Collaborators
- Saint Peters University Hospital, Community Medical Center, Toms River, NJ
- Study start
- 28 Apr 2017 (actual)
- Primary completion
- 8 Mar 2022 (actual)
- Study completion
- 8 Mar 2022 (actual)
- First posted
- 31 Jan 2019 (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.
The purpose of this study is to determine efficacy, safety of Stereotactic Body Radiotherapy (SBRT) in combination with immunotherapy in participants with metastatic non-small cell lung cancer (NSCLC) who are eligible for an immunotherapy agent.
Detailed description
Blockade of the PD-1/PD-L1 T-cell checkpoint pathway is an effective and well tolerated approach to stimulating the immune response which is a critical option in the treatment of metastatic NSCLC. However, progression free survival (PFS) is increased by only 2-4 months and median overall survival (OS) by 3-9 months.
There is compelling evidence that PFS is increased up to 3 fold and OS by 2 fold in patients receiving a course of radiation therapy while on immunotherapy. Radiotherapy is known to induce immunogenic tumor cell death and upregulation of dendritic cells and antigen presentation leading to activation of cytotoxic T-Cells. Dramatic T-cell activation has been demonstrated where tumor regression occurs outside the radiation treatment field in a phenomenon termed the abscopal effect and is associated with high dose radiation delivered via SBRT.
As such, SBRT activation of T-cells could be complementary to immunotherapy and enhance T-cell mediated killing via PD-L1 blockade which could lead to lasting and durable tumor response with improved progression free survival and overall survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Radiation: Stereotactic Body Radiotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically or cytologically confirmed Stage IV NSCLC according to the 7th AJCC staging manual.
- Eligible for an immunotherapy agent. Patients who progress after drug therapy (3 months) for ALK, EGFR or ROS mutation positive lung cancer are eligible.
- At least 2 lesions that are safely amenable to SBRT. ECOG <=2.
- At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for response assessment or at least 1 lesion with FDG avidity and CT correlate that can be monitored for PET-CT response by SUV Max increase or decrease.
- Normal Hepatic and renal function.
Key exclusion criteria (10 listed)
- Patients with active CNS metastases
- Active, known or suspected auto-immune disease.
- Patients with medical conditions that require systemic immunosuppression.
- Patients with a history of interstitial lung disease.
- Prior treatment with immune checkpoint inhibitors/immonotherapy.
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 |
|---|---|---|
| Stereotactic Body RadiotherapyAlso: SBRT, SRS, SABR, CyberKnifeAll patients in this trial will be treated with fractionated Stereotactic body radiation therapy. SBRT will be delivered to <=3 sites in 3-5 fractions followed by administration of the specified immunotherapy agent (Nivolumab or Pembrolizumab). This approach will take advantage of the transient increase in antigen availability, increased antigen presentation and upregulation of PD-1 by tumor cells following ablative radiation therapy. | Radiation | Treatment Arm |
Primary outcome
Overall Survival
Time frame: 24 months
Determine overall survival in patients receiving SBRT and immunotherapy as compared to landmark trials of patients receiving immunotherapy alone (Checkmate 057, Keynote 024)
Acute Toxicity: Radiation pnuemonitis measured using NCI CTCAE version 4.0
Time frame: 0-15 weeks
Determine excess/unexpected toxicity that cannot be attributed to routine radiation therapy or immunotherapy side effects.
4 secondary outcomes
Progression Free Survival
Time frame: 3-24 Months
Local Control
Time frame: 0-24 Months
Late Toxicity: Pulmonary, Bone or Visceral organ toxicity evaluated 6 months from completion of treatment using NCI CTCAE version 4.
Time frame: 6-24 Months
Impact of Tumor Burden
Time frame: 24 Months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2023.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Stereotactic Body Radiotherapy in people with Metastatic Nonsmall Cell Lung Cancer and Non Small Cell Lung Cancer, run by Crozer-Keystone Health System at 1 site in United States.
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 11 inclusion and 10 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: finished, as of the sponsor's last update on 6 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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: 24 months). The study lists 2 primary outcomes in all. 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 6 Mar 2023; AzTrials last refreshed its copy on 6 Nov 2026.