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Immunotherapy, Chemotherapy, Radiotherapy and Surgery for Synchronous Oligo-metastatic NSCLC (CHESS)

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ClinicalTrials.gov Identifier: NCT03965468
Recruitment Status : Recruiting
First Posted : May 29, 2019
Last Update Posted : December 2, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
European Thoracic Oncology Platform

Brief 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).

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. Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 47 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Immunotherapy, chemotherapy, radiotherapy and surgery

Durvalumab 1500 mg administered intravenously every 3 weeks for the first 4-6 cycles (during chemotherapy);

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.

Drug: 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.
Other Name: Imfinzi

Drug: Carboplatin
Carboplatin belongs to the group of medicines known as alkylating agents. Carboplatin interferes with the growth of cancer cells, which eventually are destroyed.

Drug: 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).

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.




Primary Outcome Measures :
  1. Progression-free survival at 12 months [ Time Frame: Assessed from the date of enrolment to completion of treatment at 12 months. ]
    Defined as time from date of enrollment until documented progression. 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 1.1 criteria.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Time from date of enrolment until death from any cause. Assessed for up to 30 months. ]
    Defined as the time from date of enrolment until death from any cause. Censoring will occur at the last follow-up date.

  2. 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.

  3. Response to induction therapy [ Time Frame: Assessed from the start of protocol treatment until the end of the induction phase (restaging at 3-month tumour assessment). ]
    Defined as the best overall response [complete response (CR) or partial response (PR)] according to RECIST 1.1 criteria.

  4. 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.

  5. Overall response [ Time Frame: Assessed from the start of protocol treatment across all time points until the end of protocol treatment, for up to 12 months. ]
    Defined as best overall response [complete response (CR) or partial response (PR) according to RECIST 1.1 criteria.

  6. 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 or response.

  7. 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).

  8. 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; laboratory parameters and abnormalities, and vital signs.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 lymphangitiosis 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
  • Active tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
  • Active autoimmune disease 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.
  • Women who are pregnant or in the period of lactation.
  • 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.

Information from the National Library of Medicine

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


Contacts
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Contact: Barbara Ruepp, PharmD +41315119400 barbara.ruepp@ibcsg.org

Locations
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Netherlands
Maastricht University Medical Center Not yet recruiting
Maastricht, Netherlands
Contact: Dirk De Ruysscher, MD       dirk.deruysscher@maastro.nl   
Principal Investigator: Dirk De Ruysscher, MD         
Erasmus Medical Centre Not yet recruiting
Rotterdam, Netherlands
Contact: Joachim Aerts, MD       j.aerts@erasmusmc.nl   
Principal Investigator: Joachim Aerts, MD         
Spain
Hosp. De la Santa Creu i Sant Pau Not yet recruiting
Barcelona, Spain
Contact: Ivana Sullivan, MD         
Principal Investigator: Ivana Sullivan, MD         
Hosp. Uni. Virgen de las Nieves Not yet recruiting
Granada, Spain
Contact: Javier Valdivia, MD         
Principal Investigator: Javier Valdivia, MD         
Hosp. Sanchinarro- Centro Integral Oncología Clara Campal Not yet recruiting
Madrid, Spain
Contact: Ana Collazo, MD         
Principal Investigator: Ana Collazo, MD         
Hosp. Uni. Politécnico La Fe Not yet recruiting
Valencia, Spain
Contact: Oscar Juan-Vidal, MD         
Principal Investigator: Oscar Juan-Vidal, MD         
Switzerland
Inselspital Bern Recruiting
Bern, Switzerland
Contact: Amina Scherz, MD       amina.scherz@insel.ch   
Principal Investigator: Amina Scherz, MD         
HFR Fribourg Not yet recruiting
Fribourg, Switzerland
Contact: Daniel Betticher       daniel.betticher@h-fr.ch   
Principal Investigator: Daniel Betticher, MD         
Geneva University Hospital Not yet recruiting
Geneva, Switzerland
Contact: Alfredo Addeo, MD       alfredo.addeo@hcuge.ch   
Principal Investigator: Alfredo Addeo, MD         
Centre Hospitalier Universitaire Vaudois (CHUV) Not yet recruiting
Lausanne, Switzerland
Contact: Solage Peters         
Principal Investigator: Solange Peters, MD         
University Hospital Zurich Recruiting
Zurich, Switzerland
Contact: Matthias Guckenberger, MD       Matthias.Guckenberger@usz.ch   
Principal Investigator: Matthias Guckenberger, MD         
Sponsors and Collaborators
European Thoracic Oncology Platform
AstraZeneca
Investigators
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Study Chair: Matthias Guckenberger, MD-PhD University Hospital, Zürich
Study Chair: Isabelle Schmitt-Opitz, MD University Hospital, Zürich

Publications:

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Responsible Party: European Thoracic Oncology Platform
ClinicalTrials.gov Identifier: NCT03965468     History of Changes
Other Study ID Numbers: ETOP 14-18
2018-003011-22 ( EudraCT Number )
ESR-17-13224 ( Other Identifier: AstraZeneca )
First Posted: May 29, 2019    Key Record Dates
Last Update Posted: December 2, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by European Thoracic Oncology Platform:
NSCLC
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Durvalumab
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological