A phase II trial assessing the efficacy (how well the treatment works), safety and tolerability (side effects of treatment) of the antibody drug durvalumab, administered together with standard chemotherapy and radiotherapy for the treatment of non-small cell lung cancer.
- Conditions
- Synchronous oligo-metastatic Non-Small Cell Lung Cancer (NSCLC)MedDRA version: 21.1Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003011-22-IT
- Lead Sponsor
- EUROPEAN THORACIC ONCOLOGY PLATFORM
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 47
- Histological confirmed NSCLC
- Synchronous oligo-metastatic stage IV disease: max 3 distant metastases, one of which must be extra-cerebral for SBRT
- Initial mediastinal staging is recommended (except for lymph nodes <1cm on CT and PET-negative) preferably by endobronchial ultrasound (EBUS)
- Neurosurgical resection of one single CNS metastasis or laparoscopic resection of one adrenal metastasis before study inclusion is allowed (one extra-cerebral metastass must be available for SBRT)
- Able to understand and give written informed consent and comply with study procedures
- Age =18 years
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 27
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
- Prior chemotherapy, radiotherapy or therapeutical surgery for NSCLC (an exception is the resection of one single CNS or adrenal metastasis)
- Activating driver mutation: EGRF, ALK, ROS1
- >3 distant metastases
- Brain metastases not amendable for radiosurgery or neurosurgery - Extracranial metastatic locations such as malignant ascites, pleural or pericardial effusion, diffuse lymphangitiosis of skin or lung, diffuse bone marrow metastasis, abdominal masses/abdominal organomegaly, identified by physical examination that is not measurable by reproducible imaging techniques.
- Primary lung cancer not suitable for radical therapy (pneumonectomy excluded)
- History of leptomeningeal carcinomatosis
- Major surgery or significant traumatic injury from which the patient has not recovered at least 28 days before enrolment
- Any uncontrolled intercurrent illness, including but not limited to: ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease or serious chronic gastrointestinal conditions associated with diarrhea, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol
- Active infection including tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
- Active autoimmune disorders requiring systemic treatment
- Severe or uncontrolled cardiac disease requiring treatment
- History of primary immunodeficiency
- History of allogeneic organ transplant
- Receipt of live attenuated vaccines within 30 days prior to enrolment
- Known allergies or hypersensitivity to trial drugs or to any excipient
- Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the trial and for up to 90 days after last dose of durvalumab.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate PFS in synchronous oligometastatic NSCLC patients treated with induction immunotherapy, chemotherapy and stereotactic body radiation therapy (SBRT) to all metastases followed by definitive surgery or radiotherapy to the locoregional primary tumour .;Secondary Objective: 1) To evaluate secondary measures of clinical efficacy, overall survival, pattern of disease progression, response to induction therapy, overall response and duration of response.<br>2) To assess the safety and tolerability of the treatment.<br>3) To evaluate symptom-specific and global quality of life.;Primary end point(s): Progression-free survival at 12 months;Timepoint(s) of evaluation of this end point: after 12 months (±2 weeks) from start of durvalumab treatment.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Duration of response; Toxicity before and after surgery/radiotherapy; Symptom-specific and global quality of life; Response to induction therapy; Overall response (OR); Overall survival (OS); Pattern of disease progression; Distant progression-free survival;Timepoint(s) of evaluation of this end point: from date of first objective response to date of first progression or relapse; from date enrolment until 90 days after treatment discontinuation; at baseline; 3 weeks and 3 months after treatment start. For patients without disease progression at restaging: before definitive local treatment and 6, 9 and 12 months after treatment start.; best overal response evaluated from start of treatment until end of induction phase (restaging at 3-month); from start of treatment until treatment discontinuation; from enrolment date until death from any cause.; site of first progression evaluated up to one year after enrollment.; development of new metastases across all timepoints