Etude : ImmunoSABR / ImmunoSABR2



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Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : ImmunoSABR

Nom : ImmunoSABR2

Traitement : Métastatique ou localement avancé / Radiothérapie

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 28/04/2020
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Étude de phase II portant sur la combinaison d’une immunothérapie L19-IL2 et d’une radiothérapie (stéréotaxique d'ablation) chez des patients atteints d’un carcinome pulmonaire non à petites cellules métastasé

Spécialité : Organes respiratoires et intrathoraciques
Localisation : C34 - Tumeur maligne des bronches et du poumon
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : IMMUNOSABR will include 126 patients. In this single-stage controlled randomised open-label phase II trial, we aim to demonstrate an absolute increase in progression-free survival (primary endpoint). PFS will be determined as the time between randomisation 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 immunocytokine) and experimental arms (with immunocytokine 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 18 months (or 1.5 years), making the total study duration 47 months. Comparison between control and experimental arms will be made using the Log-Rank statistic. This test for superiority will be one-sided with the desired type I error of 0.10 and power of 0.90.

Patients enrolled in the trial will be randomised into the control arm (C-arm) or experimental arm (E-arm).
- C-arm: Standard of Care (SOC) according to the local and national guidelines: (wait and see or surgery and/or chemotherapy and/or standard (symptomatic) radiotherapy and/or SABR, oligometastatic disease.
- E-arm: Standard of Care (SOC) SABR (oligometastatic disease) or radiotherapy (diffuse disease) + L19-IL2 up to 6 cycles (+ aPD(L)1 if SOC)

The expected 1.5-year PFS is 15% in the C-arm and 35% in the E-arm. A sample size of 116 patients (58 patients per treatment arm) is needed to show this difference of 20% in PFS, using a logrank test with a two-sided alpha of 0.05 and power of 85%. Patients will be evenly divided over the two arms. Assuming a drop-out rate of 10%, a total of 126 patients (63 per arm) need to be included.

Primary objective The main objective of the trial is to test if the activity of the combination of (SAB)R and L19-IL2 in patients with metastatic NSCLC will result in improved progression-free survival (PFS) compared to the SOC.

Secondary Objectives
- Assessment of the PFS of the patient cohort, at 5 years after randomisation.
- Assessment of the overall survival of the patient cohort, at 5 years after randomisation.
- To assess the toxicity of this treatment schedule;
- To assess Quality of Life (QoL);
- To assess the occurrence of an Out of Field Radio-Immune (OFRI) response / abscopal effect using imaging;
- To assess the occurrence of an In Field Radio-Immune (IFRI) response using imaging;
- To perform correlative biomarker studies related to treatment response.

Exploratory endpoints:
- Correlative biomarker studies:
Tumour tissue: e.g EDB expression, non-synonymous mutations, immune monitoring;
Blood: e.g. EDB expression, cfDNA, and immune monitoring;
Radiomics on CT and if available MRI;
Faeces: diversity in microbiota.
- iRECIST
- Tumour grow kinetics

Phase : II

Stade : Métastatique

1, 2, 3
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : 1. Oligometastatic disease (≤5 metastasis)
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Histological confirmed limited metastatic adult NSCLC patients, regardless of the PD-L1 status.
o Maximum of 5 metastatic lesions, maximum one brain lesion 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 prior randomisation.
- If a patient has unclear lesions in the liver or brain, an MRI would be advised following the ESMO guidelines
o In patients with 2 lung tumours, it can be unclear if the patient has 2 concurrent primary tumours or a primary lung tumour with 1 metastasis. In
this case, it is according to the decision of the local multidisciplinary tumour board whether the patient has an M1 disease or not.
• Previous treatment:
o Prior cancer treatments are allowed but must be discontinued for at least 4 weeks before randomisation.
• Age of 18 years or older.
• WHO performance status 0-1;
• Adequate bone marrow function (evaluated in the local lab): Absolute Neutrophil Count (ANC) of > or equal to 1.0 x 10 9/L, platelet count > or equal to 100 x 10 9/L, Hb > or equal 6 x10 9/L (it is allowed to give a blood transfusion if Hb is initially too low);
• 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;
• Adequate renal function (evaluated in the local lab): 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: Women of childbearing potential (WOCBP) must be using, from the screening to six months following the last study drug administration, effective contraception methods, as defined by the "Recommendations for contraception and pregnancy testing in clinical trials" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group (www.hma.eu/ctfg.html)
• Signed and dated written informed consent;


2. Poly-metastatic disease (up to 10 metastasis)
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Histological confirmed limited metastatic adult NSCLC patients, regardless of the PD-L1 status.
o A minimum of 6 and maximum of 10 metastatic lesions, maximum two brain lesions are 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 prior to randomisation.
- If a patient has unclear lesions in the liver or brain an MRI would be advised following the ESMO guidelines.
o Controlled disease (i.e. no progressive disease according to RECIST 1.1) following primary platinum-based chemotherapy, with at least one measurable lesion (according to RECIST 1.1) that has no overlap with the PTV of the lesion subjected to radiotherapy.
• Previous treatment:
o Patient inclusion is allowed from 4 weeks to 8 weeks following the last platinum-based chemotherapy infusion (first line or second line). In case of maintenance chemotherapy, this therapy will only be started after the end of the L19-IL2 treatment Patients receiving second-line platinum-based chemotherapy following primary treatment with a PD-(L)1 inhibitor is allowed.
• Age of 18 years or older.
• WHO performance status 0-1;
• Adequate bone marrow function (evaluated in the local lab) : Absolute Neutrophil Count (ANC) of > or equal to 1.0 x 10 9/L, platelet count > or equal to 100 x 10 9/L, Hb > or equal 6 x10 9/L (it is allowed to give a blood transfusion if Hb is initially too low);
• 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;
• Adequate renal function (evaluated in the local lab): 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: Women of childbearing potential (WOCBP) must be using, from the screening to six months following the last study drug administration, effective contraception methods, as defined by the "Recommendations for contraception and pregnancy testing in clinical trials" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group (www.hma.eu/ctfg.html)
• Signed and dated written informed consent;

Critères de non-inclusion : 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:
• More than 10 metastatic lesions
• Patients with pleuritis, pericarditis and peritonitis carcinomatosis
• Patients who are already actively participating in another study.
• 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.
• Previous radiotherapy to an area that would be re-treated by (SAB)R, resulting in overlap of the high dose areas;
• Patients with progressive disease following first line or second line chemotherapy.
• 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.
• 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).
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.
• Systemic treatment with either corticosteroid (>10 mg daily prednisone equivalents) or other 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.
• Acute or sub-acute coronary syndromes within the last year, acute inflammatory heart disease, heart insufficiency NYHA > 2, or irreversible cardiac arrhythmias;
• An 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 from the screening will be acceptable in the absence of intercurrent use of potentially cardiotoxic treatment or cardiac medical history).
• Uncontrolled hypertensive disease; (systolic BP (SBP) ≥160 or diastolic BP ≥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;
• Pregnancy or breastfeeding; it is well known that ED-B, the target of both L19IL2, is expressed in a variety of fetal tissues. Therefore, it will be contra-indicated for pregnant or lactating women
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03705403
Promoteur :
Maastricht University
Type de sponsor : Institutionnel
00000 HORS FRANCE

Coordonnateur :
Professeur Philippe LAMBIN
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Oscar Lambret - 3 Rue Frédéric Combemale - 59000 LILLE

Investigateur :
Docteur David PASQUIER

TEC / ARC / IDE :
Unité Intégrée de Recherche Clinique
investigation@
o-lambret.fr
03.20.29.59.35

Statut de l'essai : OUVERT

MAJ : 28/04/2020