Immunotherapy, Chemotherapy, Radiotherapy and Surgery for Synchronous Oligo-metastatic NSCLC (CHESS)
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|ClinicalTrials.gov Identifier: NCT03965468|
Recruitment Status : Active, not recruiting
First Posted : May 29, 2019
Last Update Posted : December 15, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Non-small Cell Lung Cancer Stage IV Oligometastasis||Drug: Durvalumab Drug: Carboplatin Drug: Paclitaxel Radiation: Stereotactic body radiation therapy (SBRT) Procedure: Surgical resection - definitive local treatment. Radiation: Radical radiotherapy - definitive local treatment. Drug: Tremelimumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||96 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||November 19, 2019|
|Estimated Primary Completion Date :||August 2026|
|Estimated Study Completion Date :||December 2026|
Experimental: Immunotherapy, chemotherapy, radiotherapy and surgery
Durvalumab 1500 mg administered intravenously every 3 weeks for the first 4-6 cycles (during chemotherapy);
Tremelimumab 75mg administered intravenously every 3 weeks for the first 4-6 cycles (only cohort 2)
4-6 cycles of chemotherapy, carboplatin AUC5 every 3 weeks plus paclitaxel 175 mg/m2, every 3 weeks;
Stereotactic body radiotherapy (SBRT) of all oligo-metastatic lesions, in a maximum of 10 treatment fractions over 2 weeks, starting after week one of chemotherapy cycle 1 and completed within four weeks after start of durvalumab treatment;
Restaging at 3 months; if no disease progression, proceed to definitive local treatment (surgical resection of primary tumour or radiotherapy at a minimum dose of 60-66Gy to the primary tumour). Durvalumab continues at 1500 mg intravenously every 4 weeks until progression of disease or for a maximum of 1 year from start of treatment.
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.
Other Name: Imfinzi
Carboplatin belongs to the group of medicines known as alkylating agents. Carboplatin interferes with the growth of cancer cells, which eventually are destroyed.
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).
Radiation: Stereotactic body radiation therapy (SBRT)
SBRT of all oligo-metastatic lesions
Procedure: Surgical resection - definitive local treatment.
Surgical resection of primary tumour for patients with single station, non-bulky tumours.
Radiation: 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 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.
- Progression-free survival at 12 months [ Time Frame: 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
- Overall survival [ Time Frame: Time from date of enrolment until death from any cause. Assessed for up to 30 months. ]Overall survival (OS) is defined as the time from the date of enrolment until death from any cause. Censoring for OS (patients without reported death) will occur at the last follow-up date.
- Pattern of disease progression [ Time Frame: Assessed from the date of enrolment until progression, from enrolment up to 12 months. ]Defined as the site of first progression. None, locoregional, distant, or both locoregional and distant.
- Response to induction therapy [ Time Frame: Assessed from the start of protocol treatment until the 3-month restaging ]Defined as the best overall response [complete response (CR) or partial response (PR)] according to RECIST 1.1 criteria.
- Distant progression-free survival [ Time Frame: Assessed from the date of enrolment for up to 12 months. ]Defined as the date of development of new metastases, excluding oligometastasis diagnosed at enrolment.
- Overall response [ Time Frame: Assessed from the start of protocol treatment across all time points until the end of follow-up, assessed for up to 30 months. ]Defined as best overall response [complete response (CR) or partial response (PR) according to RECIST 1.1 criteria.
- Duration of response [ Time Frame: Assessed from the date of enrolment for up to 12 months. ]Defined as the interval from the date of first documentation of objective response (CR or PR), according to RECIST 1.1 criteria to the date of first documented progression, relapse or death from any cause.
- Symptom-specific and global quality of life: The Lung Cancer Symptom Scale [ Time Frame: Assessed at trial entry, until 6 months after treatment start and at 12 months from enrolment. ]The Lung Cancer Symptom Scale, a 9-item one page questionnaire will be used to assess change in total score (average of all 9 items).
- Toxicity before and after surgery/radiotherapy [ Time Frame: Adverse events will be collected from the date of consent until 90 days after the completion of treatment. ]Safety parameters will be assessed in terms of adverse events graded by CTCAE v5.0 including events leading to dose interruptions, withdrawals of protocol treatment and death; severe, serious and selected adverse events; deaths; clinically significant laboratory parameters and abnormalities, and vital signs.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03965468
|European Institute of Oncology|
|Istituto Oncologico Veneto - Irccs|
|Maastricht University Medical Center|
|Erasmus Medical Centre|
|Hosp. De la Santa Creu i Sant Pau|
|Hosp. Uni. Virgen de las Nieves|
|Hosp. Sanchinarro- Centro Integral Oncología Clara Campal|
|Vall d'Hebron University Hospital|
|Hosp. Uni. Politécnico La Fe|
|Geneva University Hospital|
|Centre Hospitalier Universitaire Vaudois (CHUV)|
|University Hospital Zurich|
|Study Chair:||Matthias Guckenberger, MD-PhD||University Hospital, Zürich|
|Study Chair:||Isabelle Schmitt-Opitz, MD||University Hospital, Zürich|
|Responsible Party:||ETOP IBCSG Partners Foundation|
|Other Study ID Numbers:||
2018-003011-22 ( EudraCT Number )
ESR-17-13224 ( Other Identifier: AstraZeneca )
|First Posted:||May 29, 2019 Key Record Dates|
|Last Update Posted:||December 15, 2022|
|Last Verified:||December 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Antineoplastic Agents, Phytogenic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological