The trial will consist of one cohort of adult patients with Stage IV metastatic NSCLC MedDRA version: 20.0 Level: LLT Classification code 10025044 Term: Lung cancer System Organ Class: 100000004864
Conditions
Sponsors
Maastricht University Medical Centre
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A.Oligometastatic disease (=5 metastasis): 1.Histological/cytological confirmed limited metastatic adult NSCLC patients, regardless of the PD-L1 status. oMax. of 5 metastatic lesions, max. 2 brain lesions with a total cumulative diameter of 5 cm is allowed: ?SOC baseline imaging e.g MRI and/or PET-CT and CT-brain or MRI brain and/or CT-scan with at least covering thorax-upper abdomen-brain, within 6 weeks or equal to 1.0 x 109 /L, platelet count > or equal to 100 x 109/L, Hb greater or equal 6.0 mmol/L (or 9.67 g/dL) (it is allowed to give a blood transfusion if Hb is initially too low; 7.Adequate hepatic function (evaluated in the local lab): 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); 8.Adequate renal function (evaluated in the local lab): creatinine clearance of at least 40 ml/min; 9.Adequate endocrine function: TSH based on local laboratory guidelines, FT4 based on local laboratory guidelines. Make sure lower/higher values are not the cause of medication (e.g. heparin i.v. amiodarone, lithium). 10.The patient is capable of complying with study procedures; 11.Life expectancy of at least 12 weeks; 12.Negative serum pregnancy test for women of childbearing potential. 13.Ability to comply with contraception requirements: Non-sterilised, sexually active male patient with a female partner who is of child-bearing age, must use two acceptable birth control methods like a condom combined with spermicidal cream or gel and a partner who is WOCBP must use effictive contraception as definied for WOCBP who are participants in the study as per the next paragraph. From the first dose of study medicine, during the study and at least up to 12 weeks after the last administration of the study medicine and up to 5 months after the last dose of the medicine with anti-PDL)1 as an action mechanism (if you get this product besides the study medicine), as an addition to the use, by the female partner, of as described in the following section: Women of childbearing potential (WOCBP) and WOCBP partners of male patients must be using, from the screening to three months following the last study drug administration and 5 months after last dose of anti-PD(L)1 maintenance treatment, effective contraception methods, (a) IUD (IUD) or intrauterine hormone delivery system (IUS), b) combined (with estrogen and progesterone) hormonal contraception associated with ovulation inh
Exclusion criteria
Exclusion criteria: For both groups; oligometastatic disease and poly-metastatic disease: A potential subject who meets any of the following criteria will be excluded from participation in this study: 1.More than 10 metastatic lesions 2.More than 2 brain metastatic lesions 3.Two brain metastases with a cumulative diameter larger than 5 cm 4.Patients with non-infectious pneumonitis, uncontrolled thyroid disease, pleuritis, pericarditis and peritonitis carcinomatosis. Or other mild/serious infection at screening that might need antibiotic therapy. (First treat infection, so patient can still participate after it is cleared.) 5.Patients who are already actively participating in another interventional study with an investigational product. 6.Patients who need simultaneous radiation on the primary tumour and metastatic lesion(s). For these patients it might be an option to treat the primary tumour first although this is not mandatory for this study. There must be minimal 4 weeks between last treatment and randomisation. 7.SABR to more than one brain metastasis or whole brain radiotherapy (WBRT) is not allowed, although it is accepted when given at least 4 weeks prior to randomisation or after the treatment period. Patients with stable brain metastases are not excluded. 8.Previous radiotherapy to an area that would be re-treated by (SAB)R, resulting in overlap of the high dose areas; 9.Maintenance therapy with anti-PD(L)1 treatment combined with chemotherapy is not allowed during treatment ((SAB)R and L19-IL2 cycles). 10.Other active malignancy or malignancy within the last 2 years (except localised skin basal/squamous cell carcinoma, non-muscle invasive carcinoma of the bladder or in situ carcinoma from any site); 11.Concomitantly administered glucocorticoids may decrease the activity of IL2 and therefore should be avoided. However, patients who develop life-threatening signs or symptoms may be treated with dexamethasone until toxicity resolves or reduces to an acceptable level (generally grade 1 and 2, however must be based at the research physician’s discretion). 12.History of allergy to intravenously administered L19-IL2 / proteins / peptides / antibodies / radiographic contrast media; 13.HIV positive; active HIV infection, or active hepatitis B or C (assessed in local lab). o For HBV serology: the determination of HBsAg, anti-HBsAg-Ab and anti-HBCAg-Ab is required. In patients with serology documenting previous exposure to HBV (i.e., anti-HBs Ab with no history of vaccination and/or anti-HBc Ab), negative serum HBV-DNA is required. For HCV: HCV RNA or HCV antibody test. Subjects with a positive test for HCV antibody but no detection of HCV RNA indicating no current infection are eligible. 14.Systemic treatment with either corticosteroid (>10 mg daily prednisone equivalents) or Interferon aplpha or immunosuppressive medications within 14 days prior to randomisation. Topical or inhalation steroids are allowed. If a patient needs to take unexpectedly immunosuppressive medication during the trial, it will be allowed but decreasing the dose as soon as possible is strongly advised. 15.Prior history of organ transplant, including autologous stem cell transplant. 16.Acute or sub-acute coronary syndromes within the last year, acute inflammatory heart disease, heart insufficiency NYHA > 2, or irreversible cardiac arrhythmias; 17.A known impaired cardiac function defined as left ventricular ejection fraction (LVEF) < 50 % (or below the study site’s lower limit o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of the trial is to test if the combination of (SAB)R and the immunocytokine L19-IL2 has clinical meaningful activity in patients with limited metastatic non-small cell lung cancer (NSCLC): (=10 sites, WHO 0-1). The expected activity is a systemic immune response preventing disease progression and resulting in an improvement of progression-free survival (PFS).;Secondary Objective: •Assesment of the overall survival •Toxicity •Quality of Life •To assess the occurrence of an Out of Field Radio-Immune (OFRI) response •To assess the occurrence of an In Field Radio-Immune (IFRI) response ;Primary end point(s): Primary endpoint: •Progression Free Survival (PFS) at 1.5 years after randomisation compared to the Standard of care ;Timepoint(s) of evaluation of this end point: At the end of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: • 5 years PFS • 1,5 years and 5 years Overall survival • 1,5 years toxicity, Quality of Life, Out of Filed Radio-Immune (IFRI) response and in field Radio-Immune (IFRI) response ;Timepoint(s) of evaluation of this end point: End of study | — |
Countries
Belgium, France, Germany, Italy, Netherlands, United Kingdom
Contacts
Public ContactMieke Denys
Sillar Clinical bvba
Outcome results
None listed