Immunotherapy combined with radiotherapy to treat stage IV lung cancer patients.
- Conditions
- ung cancer, non-small cell lung cancer, NSCLC, stage IVNiet-kleincellig longcarcinoom,longkanker,stadium 4stadium IVuitgezaaide longkanker
- Registration Number
- NL-OMON27928
- Lead Sponsor
- Maastricht University
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 126
Inclusion criteria for Oligometastatic disease (max 5 metastases) or Poly-metastatic disease (6-10 metastases) are different.
- For patients with Oligometastatic disease:
•Histological confirmed limited metastatic adult NSCLC patients, regardless of the PD-L1 status.
•Maximum of 5 metastatic lesions, a maximum of two brain lesion with a total cumulative diameter of 5 cm is allowed.
•Previous treatment:
oPrior cancer treatments are allowed but must be discontinued for at least 4 weeks before randomisation. In case of maintenance chemotherapy, this therapy will only be started after the end of the L19-IL2 treatment or only in case of Anti-PD(L)1 treatment, during L19-IL2 therapy.
•Age of 18 years or older.
•WHO performance status 0-1;
•Adequate bone marrow function (Absolute Neutrophil Count (ANC) of = 1.0 x 109 /L, platelet count = 100 x 109/L, Hb = 6.0 mmol/L (or 9.67 g/dL) (it is allowed to give a blood transfusion if Hb is initially too low))
•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 of at least 40 ml/min);
•The patient is capable of complying with study procedures;
•Life expectancy of at least 12 weeks;
•Negative serum pregnancy test for females of childbearing potential.
•Ability to comply with contraception requirements:
•Signed and dated written informed consent;
- For patients with Poly-metastatic disease (6 to 10 metastases):
•Histological confirmed limited metastatic adult NSCLC patients, regardless of the PD-L1 status.
•Minimum of 6 and maximum of 10 metastatic lesions, a maximum of two brain lesion with a total cumulative diameter of 5 cm is allowed.
•Previous treatment:
oThe time between the last administration of chemo and/or immunotherapy (given as first or second line standard of care treatment) and the randomisation must be at least 4 weeks. In case of maintenance chemotherapy, this therapy will only be started after the end of the L19-IL2 treatment or only in case of Anti-PD(L)1 treatment, during L19-IL2 therapy
•Age of 18 years or older.
•WHO performance status 0-1;
•Adequate bone marrow function (Absolute Neutrophil Count (ANC) of = 1.0 x 109 /L, platelet count = 100 x 109/L, Hb = 6.0 mmol/L (or 9.67 g/dL) (it is allowed to give a blood transfusion if Hb is initially too low))
•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 of at least 40 ml/min);
•The patient is capable of complying with study procedures;
•Life expectancy of at least 12 weeks;
•Negative serum pregnancy test for females of childbearing potential.
•Ability to comply with contraception requirements:
•Signed and dated written informed consent;
•More than 10 metastatic lesions.
•More than 2 brain metastatic lesions.
•2 brain metastases with a cumulative diameter larger than 5 cm.
•Patients with non-infectious pneumonitis, uncontrolled thyroid disease, pleuritis, pericarditis and peritonitis carcinomatosis
•Patients who received live vaccines 30 days or fewer prior to enrolment.
•Patients who are already actively participating in another study.
•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.
•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.
•Previous radiotherapy to an area that would be re-treated by (SAB)R, resulting in overlap of the high dose areas.
•Maintenance therapy with Anti-PD(L)1 treatment combined with chemotherapy is not allowed during treatment ((SAB)R and L19-IL2 cycles).
•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).
•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).
•History of allergy to intravenously administered proteins/peptides/antibodies/ radiographic contrast media.
•HIV positive; active HIV infection, or active hepatitis B or C (assessed in local lab).
•Systemic treatment with either corticosteroid (>10 mg daily prednisone equivalents) or Interferon alpha 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.
•Prior history of organ transplant, including autologous stem cell transplant.
•Acute or sub-acute coronary syndromes within the last year, acute inflammatory heart disease, heart insufficiency NYHA > 2, or irreversible cardiac arrhythmias.
•A known 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.
•Uncontrolled hypertensive disease; (systolic blood pressure (SBP) =160 or diastolic blood pressure (DBP) =100 mm Hg during two measurements).
•History or evidence of active autoimmune disease.
•Severe diabetic retinopathy (neoangiogenesis targeted by L19 outside the tumour).
•Major trauma, including oncologic surgery, but excluding smaller procedures like the placement of porth-à-cath or surgical biopsy, within 4 weeks prior to randomisation (neoangiogenesis targeted by L19 outside a tumour).
•Any underlying mental, 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. Unstable or serious concurrent uncontrolled medical conditions.
•Pre
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) at 1.5 years after randomisation.
- Secondary Outcome Measures
Name Time Method Secondary endpoints:<br>•PFS;<br>•Overall survival;<br>•Toxicity (CTCAE version5);<br>•Quality of Life (EORTC QLQ C30 v3.0, QLQ LC13 and EQ5D);<br>•The occurrence of OFRI / the abscopal effect using imaging, based on RECIST criteria;<br>•The occurrence of an IFRI response, based on RECIST criteria.<br><br>Exploratory endpoints:<br>•Correlative biomarker studies:<br>oTumour tissue: e.g EDB expression, non-synonymous mutations, immune monitoring,<br>oBlood: e.g. EDB expression, cfDNA, and immune monitoring<br>oRadiomics on CT and if available MRI;<br>oFaeces: diversity in microbiota.<br>•iRECIST<br>•Tumour growth kinetics