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 tremelimumab, standard chemotherapy and radiotherapy
- 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-NL
- Lead Sponsor
- ETOP IBCSG Partners Foundation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 96
- Histological confirmed NSCLC
- Measurable disease as assessed by RECIST v1.1
- 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
- Body weight >30kg
- ECOG Performance Status 0-1
- Availability of tumour tissue for translational research
- Adequate haematological, renal and liver function
- Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test within 7 days before enrolment.
- Life expectancy of =12 weeks
- Written IC for protocol treatment must be signed and dated by the patient and the investigator prior to any trial-related intervention.
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 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 41
- Prior chemotherapy, radiotherapy or therapeutical surgery for NSCLC (an exception is the resection of one single CNS or adrenal metastasis)
- Activating driver mutation: EGFR, 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 lymphangiomatosis 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 unresolved toxicities (grade =2) from previous anticancer therapy other than for NSCLC, with the exception of alopecia or vitiligo, and the laboratory values defined in the inclusion criteria:
- Patients with grade =2 neutropathy will be evaluated on a case-by-case basis after consultation with the ETOP Medical Affairs team.
- Patients with irreversible toxicity not reasonable expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with ETOP Medical Affairs team.
- 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 diarrhoea, 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 or prior documented autoimmune or inflammatory disorders requiring systemic treatment (including inflammatory bowel disease [e.g., colitis or Crohn's disease ], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis Syndrome, or Wegener Syndrome [granulomatosis with polyangiitis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]. The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patient with hypothyroidism (e.g. , following Hashimoto syndrome) stable on hormone replacement
- Any chronic skin conditions that does not require systemic therapy
- Patients without active disease in the last five years may be included but only after consultation with the study physician
- Patient with celiac disease controlled by diet alone
- Active malignancy requiring concurrent intervention
- 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
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab and tremelimumab
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method