Clinical trial NCT03540420: Atezolizumab After Concurrent Chemo-radiotherapy Versus Chemo-radiotherapy Alone in Limited Disease Small-cell Lung Cancer
Official title: A Randomized Phase II Study Comparing Atezolizumab After Concurrent Chemo-radiotherapy With Chemo-radiotherapy Alone in Limited Disease Small-cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Small-cell Lung Cancer
Keywords: Atezolizumab
Chemoradiotherapy
Immunotherapy
Lead sponsor: Norwegian University of Science and Technology
Sponsor class: OTHER
Collaborators: name: University Hospital of North Norway
name: Alesund Hospital
name: Vestre Viken Hospital Trust
name: University Hospital, Akershus
name: Helse Nord-Trøndelag HF
name: Helse Stavanger HF
name: Haukeland University Hospital
name: Sorlandet Hospital HF
name: Ullevaal University Hospital
name: Molde Hospital
name: Helse Fonna
name: Nordlandssykehuset HF
name: Volda Hospital
name: Kristiansund Hospital
name: Sahlgrenska University Hospital
name: Skane University Hospital
name: Karolinska University Hospital
name: Ôrebro University Hospital
name: Gävle Hospital
name: University Hospital, Linkoeping
name: Odense University Hospital
name: Aalborg University Hospital
name: Rigshospitalet, Denmark
name: National Cancer Center Affiliate of Vilnius University Hospital Santaros Klinikos
name: Kantonsspital Winterthur KSW
name: University Hospital, Basel, Switzerland
name: Insel Gruppe AG, University Hospital Bern
name: Kantonsspital Graubünden
name: Freiburger Spital
name: Klinik Hirslanden, Zurich
name: Kantonsspital Olten
name: Spital STS AG
name: Ente Ospedaliero Cantonale, Bellinzona
name: Cantonal Hospital of St. Gallen
name: St. Olavs Hospital
name: Oslo University Hospital
name: Rijnstate Hospital
name: Isala
name: Zuyderland Medisch Centrum
name: The Netherlands Cancer Institute
name: St. Antonius Hospital
name: Amphia Hospital
name: Medisch Spectrum Twente
name: Erasmus Medical Center
First posted: 2018-05-30
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Some patients with limited disease small-cell lung cancer (LD SCLC) are cured after chemo-radiotherapy, but the majority relapse and die from their cancer. Better therapy is needed. Immunotherapy represents the largest advance in cancer therapy in recent years and has demonstrated promising activity in SCLC. In this study we will investigate whether atezolizumab prolongs survival in LD SCLC patients who have undergone chemo-radiotherapy.

Detailed description: Patients who have

* completed 4 course of platinum/etoposide and thoracic radiotherapy of 45 Gy/30 fractions, 2 fractions per day
* non-progression after chemo-radiotherapy
* ECOG performance status 0-2

will be randomized to receive atezolizumab 1200 mg IV every 3 weeks in 12 months or standard of care (observation).

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed small-cell lung cancer
* Previous radiotherapy to the thorax is allowed as long as the patient can receive TRT of 45 Gy.
* Stage I-III according to TNM v8 ineligible for surgery provided all lesions can be included in a tolerable radiotherapy field ("limited disease")
* ECOG performance status 0-2
* Measureable disease according to the RECIST 1.1
* Adequate organ function defined as: (a) Serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN); (b) Total serum bilirubin ≤ 1.5 x ULN; (c)Absolute neutrophil count (ANC) ≥ 1.5 x 10 superscr 9/L; (d) Platelets ≥ 100 x 10 superscr 9/L ; (e) Creatinine \< 100 µmol/L and calculated creatinine-clearance \> 50 ml/min. If calculated creatinine-clearance is \< 50 ml/min, an EDTA clearance should be performed
* No malignant cells in pericardial or pleural fluid (at least 1 sample should be obtained if pleural fluid is present) If there is so little fluid that it cannot easily be collected, the patient is considered eligible.
* Pulmonary function: FEV1 \> 1 l or \> 30 % of predicted value and DLCO \> 30 % of predicted value
* Female patients of childbearing potential (Postmenarcheal, not postmenopausal (\>12 continuous months of amenorrhea with no identified cause other than menopause), and no surgical sterilization) should use highly effective contraception and take active measures to avoid pregnancy while undergoing atezolizumab treatment and for at least 5 months after the last dose. Birth control methods considered to be highly effective are listed in Appendix D of the protocol
* Written informed consent

Exclusion Criteria:

* previous systemic therapy for SCLC or immune checkpoint blockade therapy
* serious concomitant systemic disorders (for example active infection, unstable cardiovascular disease) which in the opinion of the investigator would compromise the patient's ability to complete the study, or would interfere with the evaluation of the efficacy and safety of the study treatment
* lung disease requiring systemic steroids in doses of \>10 mg prednisolone (or equivalent dose of other steroid)
* previous allogeneic or organ transplant
* active or history of autoimmune disease or immune deficiency, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis
* history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* live vaccine administered in the last 30 days
* active infection requiring IV antibiotics
* active viral hepatitis or HIV-positive
* conditions - medical, social, psychological - which could prevent adequate information and follow-up
* clinically active cancer other than SCLC with the exception of malignancies with a negligible risk of metastases or death (e.g. 5-years OS rate of \>90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer. Hormonal therapy for non-metastatic prostate or breast cancer is allowed.
* pregnant or lactating women

Primary outcomes:
measure: 2 year survival
timeFrame: 2 year after enrollment is completed
Secondary outcomes:
measure: Progression free survival
timeFrame: 2 year after enrollment is completed
measure: Best response rate during study treatment period
timeFrame: 2 year after enrollment is completed
measure: Number of treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: 13 months after last patient completed atezolizumab therapy
measure: Patient-reported Health related quality of life on the EORTC QLQ-C30 and LC13 questionnaires.
timeFrame: 2 year after enrollment is completed
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital
city: København
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital
city: Vilnius
country: Lithuania
facility: National Cancer Institute
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Ziekenhuis
city: Arnhem
country: Netherlands
facility: Rijnstate Ziekenhuis
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
city: Enschede
country: Netherlands
facility: Medische Centrum Twente
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Sittard
country: Netherlands
facility: Zuyderland Ziekenhuis
city: Utrecht
country: Netherlands
facility: Antonius Ziekenhuis
city: Zwolle
country: Netherlands
facility: Isala Ziekenhuis
city: Bergen
country: Norway
facility: Haukeland Universitetssykehus
city: Drammen
country: Norway
facility: Drammen sykehus - Vestre Viken
city: Haugesund
country: Norway
facility: Haugesund hospital
city: Kristiansand
country: Norway
facility: Sørlandet Sykehus
city: Kristiansund
country: Norway
facility: Sykehuset i Kristansund
city: Levanger
country: Norway
facility: Sykehuset Levanger
city: Molde
country: Norway
facility: Molde Sjukehus
city: Oslo
country: Norway
facility: Akershus Universitetssykehus AHUS
city: Oslo
country: Norway
facility: Oslo University Hospital Ullevål
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Tromsø
country: Norway
facility: Universitetssykehuset Nord-Norge
city: Trondheim
country: Norway
facility: Cancer Clinic at St. Olavs Hospital
city: Volda
country: Norway
facility: Volda hospital
city: Ålesund
country: Norway
facility: Ålesund Hospital
city: Gävle
country: Sweden
facility: Gävle hospital
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhus
city: Linköping
country: Sweden
facility: Universitetssjukhuset Linköping
city: Lund
country: Sweden
facility: Skånes University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Örebro
country: Sweden
facility: Universitetssjukhuset Örebro
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Bern
country: Switzerland
facility: Inselspital
city: Bern
country: Switzerland
facility: University Hospital Inselspital
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
city: Olten
country: Switzerland
facility: Kantonsspital Olten - Solothurner Spitäler
city: St Gallen
country: Switzerland
facility: Cantonal Hospital of St. Gallen
city: Thun
country: Switzerland
facility: Spital STS AG
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zürich
country: Switzerland
facility: Hirslanden Klinik
Study officials:
affiliation: Norwegian University of Science and Technology
name: Torstein B Rø, MD, PhD
role: STUDY_DIRECTOR
References: