Durvalumab: Durvalumab is a human monoclonal antibody (mAb) of the immunoglobulin G (IgG) 1 kappa subclass that inhibits binding of PD-L1. Durvalumab is expected to stimulate the patient's antitumour immune response by binding to PD L1 and shifting the balance toward an antitumour response.
Carboplatin: Carboplatin belongs to the group of medicines known as alkylating agents. Carboplatin interferes with the growth of cancer cells, which eventually are destroyed.
Paclitaxel: A compound extracted from the Pacific yew tree Taxus brevifolia with antineoplastic activity. Paclitaxel binds to tubulin and inhibits the disassembly of microtubules, thereby resulting in the inhibition of cell division. This agent also induces apoptosis by binding to and blocking the function of the apoptosis inhibitor protein Bcl-2 (B-cell Leukemia 2).
Stereotactic body radiation therapy (SBRT): SBRT of all oligo-metastatic lesions
Surgical resection - definitive local treatment.: Surgical resection of primary tumour for patients with single station, non-bulky tumours.
Radical radiotherapy - definitive local treatment.: Conventional or moderately hypo-fractionated radiotherapy to the primary tumour for other tumour stages, or in case of medical inoperability.
Tremelimumab: Tremelimumab is a human mAb of the IgG 2 subclass that is directed against CTLA-4 (CD152), a cell surface receptor that is expressed primarily on activated T-cells and acts to inhibit their activation. Tremelimumab completely blocks the interaction of human CTLA-4 with CD80 and CD86, resulting in increased release of cytokines (interleukin-2 and IFN-γ) from human T-cells, peripheral blood mononuclear cells and whole blood.
Study summary
A multicentre single arm phase II trial assessing the efficacy of immunotherapy, chemotherapy plus stereotactic radiotherapy to metastases followed by definitive surgery or radiotherapy to the locoregional primary tumour, in patients with histologically-confirmed synchronous oligo-metastatic non-small cell lung cancer (NSCLC).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Histologically confirmed non-small cell lung cancer
* Synchronous oligo-metastatic stage IV disease: maximum of three distant metastases, one of which must be extra-cerebral for stereotactic body radiotherapy (SBRT); Initial mediastinal staging is recommended (except for lymph nodes \<1 cm on CT and PET-negative) preferentially by endobronchial ultrasound (EBUS); Neurosurgical resection of one single central nervous system (CNS) metastasis or laparoscopic resection of one adrenal metastasis before study inclusion is allowed (one extra-cerebral metastasis must be available for SBRT)
* Able to understand and give written informed consent and comply with study procedures
* Age ≥18 years
* ECOG Performance Status 0-1
* Availability of tumour tissue for translational research
* Adequate haematological, renal and liver function
Exclusion Criteria:
* Prior chemotherapy, radiotherapy or therapeutic surgery for NSCLC (an exception is the resection of one single CNS or adrenal metastasis, as above)
* Activating driver mutation: epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), proto-oncogene receptor tyrosine kinase (ROS1)
* More than three distant metastases
* Brain metastases not amendable for radiosurgery or neurosurgery
* Extracranial metastatic locations such as malignant ascites, pleural or pericardial effusion, diffuse lymphangiomatosis of skin or lung, diffuse bone marrow metastasis, abdominal masses/abdominal organomegaly, identified by physical exam 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
* Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc) at screening.
* Known positivity for human immunodeficiency virus (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice)
* Active autoimmune disease requiring systemic treatment
* Severe or uncontrolled cardiac disease requiring treatment
* History of active 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.
* Women who are pregnant or in the period of lactation.
* Sexually active men and women of childbearing potential who are not willing to use a highly effective contraceptive method during the trial and up to 90 days after last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab and tremelimumab combination therapy
Primary outcome measure(s)
Progression-free survival at 12 months — Assessed from the date of enrolment to completion of treatment at 12 months. The PFS rate at 1-year is the primary endpoint of this trial and it is defined as the rate of patients without a PFS event at 1-year after enrolment. The rate will be estimated as the percentage of patients without a PFS event over the total number of patients who have completed a 1-year follow-up period after the enrolment. PFS is defined as the time from the date of enrolment until documented progression or death, if progression is not documented. Progression is defined as the development of new metastatic lesions or local progression of resected or irradiated metastases or primary tumour, assessed according to RECIST criteria version 1.1
Trial sites (14)
Facility
City
Region
Status
Istituto Oncologico Veneto - Irccs
Padova
Italy
IRCCS Istituto Nazionale Tumori Regina Elena
Roma
Italy
Maastricht University Medical Center
Maastricht
Netherlands
Erasmus Medical Centre
Rotterdam
Netherlands
Hosp. De la Santa Creu i Sant Pau
Barcelona
Spain
Hosp. Uni. Virgen de las Nieves
Granada
Spain
Hosp. Sanchinarro- Centro Integral Oncología Clara Campal
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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