Combination of immunotherapy, chemotherapy, radiotherapy, and surgery for advanced lung cancer
A Multicentre Single Arm Phase II Trial Assessing the Efficacy of Immunotherapy, Chemotherapy and Stereotactic Radiotherapy to Metastases Followed by Definitive Surgery or Radiotherapy to the Primary Tumour, in Patients With Synchronous Oligo-metastatic Non-small Cell Lung Cancer
This study is testing a new treatment plan that combines immunotherapy, chemotherapy, and targeted radiation to see if it helps people with advanced lung cancer live longer without their cancer getting worse.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 96 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | ETOP IBCSG Partners Foundation Research network |
| Drugs / interventions | durvalumab, tremelimumab, chemotherapy, immunotherapy, radiation |
| Locations | 15 sites (Milano and 14 other locations) |
| Trial ID | NCT03965468 on ClinicalTrials.gov |
What this trial studies
This phase II trial evaluates the effectiveness of a treatment regimen combining immunotherapy, chemotherapy, and stereotactic radiotherapy for patients with synchronous oligo-metastatic non-small cell lung cancer (NSCLC). Participants will receive a combination of durvalumab, carboplatin, and paclitaxel, along with targeted radiotherapy to metastatic sites, followed by definitive surgery or additional radiotherapy to the primary tumor. The goal is to reduce systemic progression and enhance progression-free survival in patients with limited metastatic disease. The study aims to leverage recent advancements in cancer treatment to improve outcomes for this patient population.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed synchronous oligo-metastatic NSCLC and a maximum of three distant metastases.
Not a fit: Patients who have previously undergone chemotherapy, radiotherapy, or therapeutic surgery for NSCLC may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly improve survival rates and quality of life for patients with advanced lung cancer.
How similar studies have performed: Other studies have shown promising results with similar combinations of immunotherapy and targeted therapies in NSCLC, indicating potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Milano and 14 other locations
- European Institute of Oncology — Milano, Italy (Recruiting)
- Istituto Oncologico Veneto - Irccs — Padova, Italy (Recruiting)
- IRCCS Istituto Nazionale Tumori Regina Elena — Roma, Italy (Recruiting)
- Maastricht University Medical Center — Maastricht, Netherlands (Recruiting)
- Erasmus Medical Centre — Rotterdam, Netherlands (Recruiting)
- Hosp. De la Santa Creu i Sant Pau — Barcelona, Spain (Recruiting)
- Hosp. Uni. Virgen de las Nieves — Granada, Spain (Recruiting)
- Hosp. Sanchinarro- Centro Integral Oncología Clara Campal — Madrid, Spain (Recruiting)
- Vall d'Hebron University Hospital — Madrid, Spain (Recruiting)
- Hosp. Uni. Politécnico La Fe — Valencia, Spain (Recruiting)
- Inselspital Bern — Bern, Switzerland (Recruiting)
- Geneva University Hospital — Geneva, Switzerland (Recruiting)
- Centre Hospitalier Universitaire Vaudois (CHUV) — Lausanne, Switzerland (Active_not_recruiting)
- Kantonsspital Winterthur — Winterthur, Switzerland (Recruiting)
- University Hospital Zurich — Zurich, Switzerland (Recruiting)
Study contacts
- Study coordinator: Barbara Ruepp, PharmD
- Email: barbara.ruepp@etop.ibcsg.org
- Phone: +41315119400
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.