NSCLC Stage IVPhase 2ImmunoSABRNCT02735850
Combination of SABR and L19-IL2 in Patients With Stage IV Lung Cancer (ImmunoSABR)
A Phase 2 study testing L19-IL2 and SBRT in people with NSCLC Stage IV and Limited Metastatic Disease, run by Maastricht Radiation Oncology at 1 site in Netherlands.
Trial summary
This will be a phase II trial testing if the combination of SBRT and L19-IL2 improves the progression free survival in patients with limited metastatic non-small cell lung cancer (NSCLC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC Stage IV, Limited Metastatic Disease
- What is being tested?
- L19-IL2 and SBRT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteNetherlands
- Study dates
- Dec 2015to Jun 2021
- 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
- Histological confirmed limited metastatic NSCLC patients. Two cohorts of patients are allowed:
- Synchronous oligometastatic eligible for ablative stereotactic body radiotherapy to all sites. These patients will have a maximum of 3 metastatic lesions (excluding the brain) eligible for ablative treatment using SABR.,
- Other oligometastatic patients with up to 10 metastatic lesions, not eligible for ablative stereotactic body radiotherapy, that have controlled disease (i.e. no progressive disease according to RECIST 1.1) following primary chemotherapy with a platinum doublet, with at least one measurable lesion that is not subjected to stereotactic body radiotherapy (SABR),.
- Radiological images documenting this lesion should be no older than 28 days before study enrolment.
- Age of 18 y or older.
- Prior treatments are allowed but must be discontinued for at least 4 weeks before enrolment.
Show all 15Show fewer
- All radiology studies must be performed within 28 days prior to registration
- WHO performance status 0-2;
- Adequate bone marrow: Normal white blood cell count and formula, normal platelet count, no anemia requiring blood transfusion or erythropoietin;
- Adequate hepatic function: total bilirubin ≤ 1.5 x upper limit of normal (ULN) for the institution; ALT, AST, and alkaline phosphatase ≤ 2.5 x ULN for the institution or <= 5 in case of liver metastasis);
- Adequate renal function: creatinine clearance at least 60 ml/min;
- The patient is capable of complying with study procedures;
- Life expectancy of at least 12 weeks;
- Men and women with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 12 weeks after the last dose of study medication.
- Signed and dated written informed consent;
Who cannot join
- NSCLC with activating ALK/EGFR of ROS mutations.
- SABR required to brain metastasis
- Previous chemotherapy other than a platinum doublet.
- Patients with progressive disease following initial chemotherapy.
- Previous chemotherapy for more than 25 weeks.
- Previous radiotherapy to an area that would be re-treated by SABR;
Show all 19Show fewer
- Other active malignancy or malignancy within the last 2 years (with exception of localized skin basal/squamous cell carcinoma, bladder in situ carcinoma);
- History of allergy to intravenously administered proteins/peptides/antibodies;
- HIV infection, active infection, or active hepatitis;
- Chronic systemic use of corticosteroids used in the management of cancer or non-cancer-related illness;
- Acute or sub-acute coronary syndromes within the last year, acute inflammatory heart disease, heart insufficiency or irreversible cardiac arrhythmias;
- Impaired cardiac function defined as left ventricular ejection fraction (LVEF) < 50 % (or below the study site's lower limit of normal) as measured by MUGA or ECHO. (LVEF measurements dating back up to 8 weeks will be acceptable in the absence of intercurrent use of potentially cardiotoxic treatment or cardiac medical history).
- Uncontrolled hypertensive disease
- History or evidence of active autoimmune disease;
- Severe diabetic retinopathy (neoangiogenesis targeted by L19 outside the tumor)
- Major trauma, including surgery, within 4 weeks prior to entering the study (neoangiogenesis targeted by L19 outside the tumor)
- Any underlying medical or psychiatric condition which in the opinion of the investigator will make administration of study drug hazardous or hinder the interpretation of study results (e.g., AE);
- Unstable or serious concurrent uncontrolled medical conditions;
- Pregnancy or breast-feeding.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Phase II Trial of the Combination of SBRT With L19-IL2 in Patients With Limited Metastatic Non-small Cell Lung Cancer (NSCLC)
This will be a phase II trial testing if the combination of SBRT and L19-IL2 improves the progression free survival in patients with limited metastatic non-small cell lung cancer (NSCLC). Treatment will be divided in two cohorts: patients eligible for ablative stereotactic body radiotherapy to all metastatic sites (treatment with curative intent) and patients not eligible for stereotactic body radiotherapy to all sites (life prolongation).
Read the detailed description
IMMUNOSABR will include 138 patients. The trialpopulation will be divided in two cohorts: patients eligible for ablative stereotactic body radiotherapy to all metastatic sites (treatment with curative intent) and patients not eligible for stereotactic body radiotherapy to all sites (life prolongation).In this single stage phase II trial we aim to demonstrate absolute increase in progression free survival at two years. . PFS will be determined as the time between randomization and disease progression, according to RECIST 1.1, death due to any cause or last patient contact alive and progression-free. Patients will be randomized between control (no L19-IL2) and experimental arms (with L19-IL2) in a 1:1 ratio. The accrual period will be 29 months (or 2.41 years) and the minimum follow-up will be 24 months (or 2 years), making the total study duration 53 months (or 4.41 years). Comparison between control and experimental arms will be done using the Log-Rank statistic. This test for superiority will be one-sided with a desired type I error of 0.10 and power of 0.80. The randomization allocation is 1:1.
Primary endpoint and power calculation For the ablative cohort: the expected 2-year PFS is 20% in the control arm (arm A) and 40% in the experimental arm ( arm B). The study is therefore powered to test for a difference in PFS at 2 years of 20%. The null hypothesis (H0) is that there is no difference in PFS between arm A and arm B. This results in a sample size of 72 patients evenly divided over two arms with 36 patient per arm. Considering a dropout rate of 10% from current experience, the actual amount of patients will be 40 per arm or 80 in total.
For the non-ablative cohort: the expected 2-year PFS is 10% in the control arm (arm C) and 30% in the experimental arm (arm D) The study is therefore powered to test for a difference in PFS at 2 years of 20%. The null hypothesis (H0) is that there is no difference in PFS between arm C and arm D. This resuls in a sample size of 52 patients evenly divided over two arms with 26 patient per arm. Considering a dropout rate of 10% from current experience, the actual amount of patients will be 29 per arm or 58 in total.
The total number of patients needed for the trial is the sum of the amount of patients in the ablative cohort (80 patients) and the amount of patients in the non-ablative cohort (58 patients): 138 patients.
Secondary endpoints Simple univariate comparisons of outcome and toxicity will be made between both treatment arms in each cohort using Chi-square tests for categorical data and independent samples t-tests for scale data. Secondary study parameter(s): Overall survival (OS) will be assessed using survival tables and Kaplan-Meier curves. OS will be calculated from the day of randomisation. Abscopal response, which can only be measured in the non-ablative cohort (with at least one non-irradiated target lesion) will measured as best response between experimental and standard treatment arms. Quality of life (EORTC QLQ-C30 version 3.0 and QLQ-LC13 questionnaires) will be recorded at regular intervals. Average changes in quality of life will be reported in terms of absolute differences in scores, and also in terms of minimally clinically relevant changes.
- Conditions
- NSCLC Stage IV, Limited Metastatic Disease
- Being tested
- L19-IL2, SBRT, No intervention
- 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.
L19-IL2Drug
L19-IL2 added to SBRT
SBRTRadiation
No interventionOther
| Study group | Role | What they receive |
|---|---|---|
| Ablative SBRT to all (max 3) sites followed by L19-IL2 | Experimental | Ablative cohort Receives: Drug: L19-IL2; Radiation: SBRT |
| Ablative SBRT to all (max 3) sites | Active comparator | Ablative cohort Receives: Radiation: SBRT |
| SBRT 1 site, L19-IL2 and then standard of care | Experimental | Non-ablative cohort Receives: Radiation: SBRT |
| Standard of care | Active comparator | Non-ablative cohort Receives: Other: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improved progression free survival
Test the combination of SBRT and L19-IL2 in progression free survival (follow-up visit)
Measured: 2 years after treatment
Secondary outcomes (5)
Overall survival
Follow-up visit
Measured: 2 years after treatment
Quality of life
Questionnaire
Measured: 2 years after treatment
Abscopal responses defined as partial or complete remission to RECIST 1.1 of lesions outside the radiotherapy field (only possible in the non-ablative cohort)
Scan
Measured: 20 weeks (during treatment)
Associative biomarkers
Blood withdrawal. ED-B of fibronectin (periferal blood), changes in the different fractions of periferal blood, mononuclear cells like cytotoxic T-cells, NK cells, memory T-cells (periferal blood), inflammatory cytokines (periferal blood). ED-B expression in the tumor (biopsies), HLA class I expression (tumor biopsies).
Measured: 20 weeks (during treatment)
Determination of hypoxia status by [18F]HX4-Positron Emmission Tomography (PET) (optional)
Scan
Measured: 20 weeks (during treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2016 (estimated)
- Study startDec 2015 (estimated)
- Primary completionFeb 2021 (estimated)
- Study completionJun 2021 (estimated)
Why it stopped: Not yet submitted, unclear timelines
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLC Stage IVStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht Radiation Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- Maastricht University Medical Center, Karolinska Institutet, University of Oxford, KU Leuven, Copenhagen University Hospital at Herlev, Catholic University of the Sacred Heart, The Netherlands Cancer Institute
- Responsible party
- Sponsor
- Investigators
- Philippe Lambin, MD, PhD, Principal investigator, Maastro Clinic, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02735850
- Sponsor's protocol ID
- Oligometa's L19-IL2
- Acronym
- ImmunoSABR
- Status last verified
- Apr 2016
- First submitted
- 22 Mar 2016
- Last updated
- 23 May 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Trial of the Combination of SBRT With L19-IL2 in Patients With Limited Metastatic Non-small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT02735850
- Acronym / sponsor ID
- ImmunoSABR / Oligometa's L19-IL2
- Conditions
- NSCLC Stage IV, Limited Metastatic Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Not yet submitted, unclear timelines
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Maastricht Radiation OncologyUniversity, hospital or other
- Collaborators
- Maastricht University Medical Center, Karolinska Institutet, University of Oxford, KU Leuven, Copenhagen University Hospital at Herlev, Catholic University of the Sacred Heart, The Netherlands Cancer Institute
- Study start
- Dec 2015 (estimated)
- Primary completion
- Feb 2021 (estimated)
- Study completion
- Jun 2021 (estimated)
- First posted
- 13 Apr 2016 (estimated)
- 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 will be a phase II trial testing if the combination of SBRT and L19-IL2 improves the progression free survival in patients with limited metastatic non-small cell lung cancer (NSCLC). Treatment will be divided in two cohorts: patients eligible for ablative stereotactic body radiotherapy to all metastatic sites (treatment with curative intent) and patients not eligible for stereotactic body radiotherapy to all sites (life prolongation).
Detailed description
IMMUNOSABR will include 138 patients. The trialpopulation will be divided in two cohorts: patients eligible for ablative stereotactic body radiotherapy to all metastatic sites (treatment with curative intent) and patients not eligible for stereotactic body radiotherapy to all sites (life prolongation).In this single stage phase II trial we aim to demonstrate absolute increase in progression free survival at two years. . PFS will be determined as the time between randomization and disease progression, according to RECIST 1.1, death due to any cause or last patient contact alive and progression-free. Patients will be randomized between control (no L19-IL2) and experimental arms (with L19-IL2) in a 1:1 ratio. The accrual period will be 29 months (or 2.41 years) and the minimum follow-up will be 24 months (or 2 years), making the total study duration 53 months (or 4.41 years). Comparison between control and experimental arms will be done using the Log-Rank statistic. This test for superiority will be one-sided with a desired type I error of 0.10 and power of 0.80. The randomization allocation is 1:1.
Primary endpoint and power calculation For the ablative cohort: the expected 2-year PFS is 20% in the control arm (arm A) and 40% in the experimental arm ( arm B). The study is therefore powered to test for a difference in PFS at 2 years of 20%. The null hypothesis (H0) is that there is no difference in PFS between arm A and arm B. This results in a sample size of 72 patients evenly divided over two arms with 36 patient per arm. Considering a dropout rate of 10% from current experience, the actual amount of patients will be 40 per arm or 80 in total.
For the non-ablative cohort: the expected 2-year PFS is 10% in the control arm (arm C) and 30% in the experimental arm (arm D) The study is therefore powered to test for a difference in PFS at 2 years of 20%. The null hypothesis (H0) is that there is no difference in PFS between arm C and arm D. This resuls in a sample size of 52 patients evenly divided over two arms with 26 patient per arm. Considering a dropout rate of 10% from current experience, the actual amount of patients will be 29 per arm or 58 in total.
The total number of patients needed for the trial is the sum of the amount of patients in the ablative cohort (80 patients) and the amount of patients in the non-ablative cohort (58 patients): 138 patients.
Secondary endpoints Simple univariate comparisons of outcome and toxicity will be made between both treatment arms in each cohort using Chi-square tests for categorical data and independent samples t-tests for scale data. Secondary study parameter(s): Overall survival (OS) will be assessed using survival tables and Kaplan-Meier curves. OS will be calculated from the day of randomisation. Abscopal response, which can only be measured in the non-ablative cohort (with at least one non-irradiated target lesion) will measured as best response between experimental and standard treatment arms. Quality of life (EORTC QLQ-C30 version 3.0 and QLQ-LC13 questionnaires) will be recorded at regular intervals. Average changes in quality of life will be reported in terms of absolute differences in scores, and also in terms of minimally clinically relevant changes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Ablative SBRT to all (max 3) sites followed by L19-IL2 | Experimental | Drug: L19-IL2, Radiation: SBRTAblative cohort |
| Ablative SBRT to all (max 3) sites | Active comparator | Radiation: SBRTAblative cohort |
| SBRT 1 site, L19-IL2 and then standard of care | Experimental | Radiation: SBRTNon-ablative cohort |
| Standard of care | Active comparator | Other: No interventionNon-ablative cohort |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histological confirmed limited metastatic NSCLC patients. Two cohorts of patients are allowed:
- Radiological images documenting this lesion should be no older than 28 days before study enrolment.
- Age of 18 y or older.
- Prior treatments are allowed but must be discontinued for at least 4 weeks before enrolment.
- All radiology studies must be performed within 28 days prior to registration
Key exclusion criteria (19 listed)
- NSCLC with activating ALK/EGFR of ROS mutations.
- SABR required to brain metastasis
- Previous chemotherapy other than a platinum doublet.
- Patients with progressive disease following initial chemotherapy.
- Previous chemotherapy for more than 25 weeks.
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 |
|---|---|---|
| L19-IL2L19-IL2 added to SBRT | Drug | Ablative SBRT to all (max 3) sites followed by L19-IL2 |
| SBRT | Radiation | Ablative SBRT to all (max 3) sites, Ablative SBRT to all (max 3) sites followed by L19-IL2, SBRT 1 site, L19-IL2 and then standard of care |
| No intervention | Other | Standard of care |
Primary outcome
Improved progression free survival
Time frame: 2 years after treatment
Test the combination of SBRT and L19-IL2 in progression free survival (follow-up visit)
5 secondary outcomes
Overall survival
Time frame: 2 years after treatment
Quality of life
Time frame: 2 years after treatment
Abscopal responses defined as partial or complete remission to RECIST 1.1 of lesions outside the radiotherapy field (only possible in the non-ablative cohort)
Time frame: 20 weeks (during treatment)
Associative biomarkers
Time frame: 20 weeks (during treatment)
Determination of hypoxia status by [18F]HX4-Positron Emmission Tomography (PET) (optional)
Time frame: 20 weeks (during treatment)
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 23 May 2017.
- Individual participant dataSharing planned: Undecided
Related trials for NSCLC Stage IV
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Active, not recruitingPhase 2
A Study of Investigational Agents in Participants With Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01H/KEYMAKER-U01)
Carcinoma, Non-Small-Cell Lung
Active, not recruitingPhase 2
CAN-2409 Plus Prodrug With Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC
Non Small Cell Lung Cancer
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.
Philippe Lambin, MD, PhD principal investigator
Maastro Clinic, The Netherlands
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 L19-IL2 and SBRT in people with NSCLC Stage IV and Limited Metastatic Disease, run by Maastricht Radiation Oncology at 1 site in Netherlands.
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 15 inclusion and 19 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 23 May 2017. 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 Netherlands. 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 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?
Improved progression free survival (time frame: 2 years after treatment). 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 23 May 2017.