Clinical trial NCT03542461: Early Switch Maintenance vs Delayed Second-line Nivolumab in Advanced Stage Squamous Non-small Cell Lung Cancer (NSCLC) Patients (EDEN Trial)
Official title: An Open-label, Randomized Phase III Study of Early Switch Maintenance vs DElayed Second-line Nivolumab in Advanced Stage Squamous Non Small-cell Lung Cancer (NSCLC) Patients After Standard First-line Platinum-based Chemotherapy - EDEN Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Squamous Non-small Cell Lung Cancer
Keywords: Squamous NSCLC
Nivolumab
Lead sponsor: Gruppo Oncologico Italiano di Ricerca Clinica
Sponsor class: OTHER
Collaborators: name: Mipharm S.p.A.
name: Bioikos Ambiente Srl
name: Istituto Toscano Tumori
name: Temas srl
name: Bristol Myers Squibb Srl Italia
First posted: 2018-05-31
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, randomized in a 1:1 ratio to 2 treatment arms and stratified by centre and response to first-line induction therapy (minimization method)
Primary purpose: TREATMENT

Brief summary: The study's hypothesis is that using Nivolumab as early switch maintenance, after 4-6 cycles of standard first-line chemotherapy, might improve survival in patients with advanced stage squamous NSCLC.


Eligibility criteria: Inclusion Criteria:

* pathologically (histology or cytology) confirmed diagnosis of squamous non-small cell lung cancer (NSCLC)
* histologically or cytologically confirmed stage IIIB-IV or recurrent squamous NSCLC with partial response (PR), complete response (CR) or stable disease (SD) according RECIST 1.1 after 4-6 courses of standard platinum-based chemotherapy (i.e. cisplatin or carboplatin combined with either paclitaxel, docetaxel, nab-paclitaxel, gemcitabine or vinorelbine)
* life expectancy ≥ 12 weeks
* Eastern Cooperative Oncology Group (ECOG) performance status (PF) of 0-2
* last chemotherapy course completed within 8 weeks before randomization and radiological assessment for tumor evaluation after first-line chemotherapy within 4 weeks before randomization
* in case of presence of treated brain metastases, lesions should be stable for at least 4 weeks, steroids should be off or on stable dose (≤ 10 mg of prednisone or equivalent), radiotherapy should have been completed at least 14 days before randomization and any Adverse Event (AE) related to radiotherapy recovered to grade \< 1 (except alopecia)
* in case of females: postmenopausal status (at least 12 months after last menstrual period should have been passed) before the screening visit or surgical sterilization. Women of childbearing potential (WOCBP) must use 2 effective methods of contraception (from the time of informed consent signature trough 30 days after last trial drug dose) or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. Pregnancy should be avoided for 23 weeks after the last trial drug dose. WOCBP must have negative serum or urine pregnancy test within 24 hours prior to the start of trial drug treatment.
* in case of males: even if surgically sterilized, effective barrier contraception (method with failure rate \< 1%/year) during the entire study treatment period and for a period of 31 weeks after the last dose of trial drug, or practice true abstinence when this is in line with the preferred and usual lifestyle of the subject.
* laboratory parameters measured within 14 days prior randomization as follows: absolute neutrophil count ≥ 1000/mmc platelet count ≥ 75000/mmc haemoglobin ≥ 9g/dL total bilirubin ≤ 1.5x the Upper Normal Limit (local laboratory range) except in case of Gilbert Syndrome where total bilirubin value \< 3.0 mg/dL is allowed serum alanine aminotransferase or aspartate aminotransferase or aspartate aminotransferase ≤ 3x the Upper Normal Limit (local laboratory range) creatinine ≤ 1.5x the Upper Normal Limit or estimated creatinine clearance using Cockcroft-Gault formula ≥ 30 mL/minute for patients with creatinine levels above institutional limits
* stable medical conditions, including the absence of acute exacerbations of chronic illnesses, serious infections or major surgery within 4 weeks before randomization and otherwise noted in other eligibility criteria
* ability to comply with protocol requirements
* ability to provide written informed consent

Exclusion Criteria:

* prior treatment with nivolumab or any other immunotherapy agent (e.g. anti-PD-1, anti-PD-L1, etc.)
* progressive disease after 4-6 cycles of first line platinum-based chemotherapy
* non-platinum-based first-line chemotherapy
* active, known or suspected autoimmune disease; please note: diabetes mellitus, hypothyroidism requiring only hormone replacement, skin disorders, such as vitiligo, psoriasis or alopecia, not requiring systemic treatment, or conditions not expected to recur without external trigger are not excluded.
* condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days prior randomization; please note: topical, ocular, intranasal and inhalational corticosteroids with minimal systemic absorption, adrenal replacement steroid doses \> 10 mg/day prednisone equivalent without concurrent autoimmune disease, brief course of corticosteroids treatment or prophylaxis or treatment of non-autoimmune conditions are allowed.
* patients with symptomatic and/or progressive brain metastases or with carcinomatous meningitis.
* previous malignancies unless complete remission has achieved at least 2 years prior to the study entry and no additional therapy is required or anticipated during the study period
* any medical condition, within 6 months before receiving the first dose of trial drug, considered relevant in the investigator's opinion. Please note: chronic stable atrial fibrillation on stable anticoagulant therapy are not excluded. Pacemaker may represent an exclusion criterion and should be discussed with the project clinician. Attention should be paid to the conditions requiring treatment with potentially hepatotoxic drugs considering the hepatotoxic potential of the trial drug.
* infection requiring an antibiotic therapy or other serious infection within 14 days before the first dose of trial drug
* positive serum pregnancy test, pregnancy or breast feeding condition (only for females)
* major surgery within 4 weeks (or 2 weeks for minor surgery) before study enrollment and not fully recovered to baseline or to a stable clinical status; lease note: insertion of vascular device is not excluded.
* interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity known history of testing positive for Human Immunodeficiency Virus (HIV) or known acquired Immunodeficiency Syndrome (AIDS)
* any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
* comorbidity or unresolved toxicities that would preclude administration of nivolumab.

Primary outcomes:
measure: Overall survival (OS)
timeFrame: From date of randomization until the date of death by any cause or study discontinuation due to lost to follow up/withdrawal of consent assessed up to 14 months .
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From date of randomization until the date of the first documented tumor progression or death by any cause, whichever occurs first, assessed up to 6 months in the arm B and 10 months in arm A.
measure: Progression-Free Survival from induction (PFSind)
timeFrame: From date of first chemotherapy cycle until the date of the first documented tumor progression or death for any cause, whichever occurs first, assessed up to 10 months in the arm B and 14 months in arm A.
measure: Time to Treatment Failure (TTF)
timeFrame: From date of randomization until the date of treatment discontinuation, assessed up to 9 months in the arm B and 14 months in arm A.
measure: Overall Survival from Induction (OSind)
timeFrame: From date of first chemotherapy cycle until the date of death, assessed assessed up to 14 months in the arm B and 18 months in arm A..
Other outcomes:
Locations:
city: Imola
country: Italy
facility: UOC Oncologia - Azienda USL di Imola - Ospedale Santa Maria della Scaletta
state: Bologna
city: Meldola
country: Italy
facility: Oncologia Medica - IRST - IRCCS di Meldola
state: Forlì
city: Lido Di Camaiore
country: Italy
facility: AUSL 12 Viareggio, Ospedale Versilia, Lido di Camaiore (LU) - Oncologia Medica
state: Lucca
city: Carpi
country: Italy
facility: UO Medicina Oncologica - Ospedale di Carpi (MO) - Azienda USL di Modena
state: Modena
city: Saronno
country: Italy
facility: UOC di Oncologia Medica - ASST Valle Olona - Presidio Ospedaliero di Saronno
state: Varese
city: Alessandria
country: Italy
facility: SC Oncologia - ASO "SS Antonio e Biagio e Cesare Arrigo"
city: Bergamo
country: Italy
facility: UO Oncologia Medica - A.S.S.T. Papa Giovanni XXIII di Bergamo
city: Bologna
country: Italy
facility: UO di Oncologia Medica - Azienda Ospedaliero-Universitaria S. Orsola Malpighi
city: Bolzano
country: Italy
facility: Divisione di Oncologia Medica - Ospedale di Bolzano
city: Brindisi
country: Italy
facility: UOC Oncologia Medica - PO A.Perino ASL di Brindisi
city: Cremona
country: Italy
facility: SC di Oncologia - Istituti Ospitalieri di Cremona
city: Cuneo
country: Italy
facility: Dipartimento di Oncologia Medica - Azienda Ospedaliera S.Croce e Carle Cuneo - Ospedale Carle
city: Ferrara
country: Italy
facility: UO di Oncologia Ematologia - Azienda Ospedaliero Universitaria di Ferrara
city: Firenze
country: Italy
facility: S.C. Oncologia Medica 1 - Azienda Ospedaliero Universitaria Careggi
city: Genova
country: Italy
facility: UOS Tumori Polmonari - IRCCS AOU San Martino -IST- Istituto Nazionale per la Ricerca sul Cancro
city: Lucca
country: Italy
facility: Azienda USL Toscana nord ovest - Ospedale San Luca di Lucca - Dipartimento Oncologico
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena - Policlinico - Dipartimento di Scienze Mediche e Chirurgiche, Materno Infantili e dell'adulto
city: Monza
country: Italy
facility: SC di Oncologia Medica - A.O. San Gerardo
city: Napoli
country: Italy
facility: U.O.C Pneumologia ad Indirizzo Oncologico - AORN Ospedali dei Colli Monaldi
city: Padova
country: Italy
facility: IOV Istituto Oncologico Veneto - UOC di Oncologia Medica 2
city: Parma
country: Italy
facility: UOC di Oncologia Medica - Azienda Ospedaliero Universitaria di Parma
city: Perugia
country: Italy
facility: S.C. di Oncologia Medica - Ospedale S.Maria della Misericordia
city: Piacenza
country: Italy
facility: AUSL - Piacenza - Ospedale "Guglielmo da Saliceto"-Dip.Oncologia e Ematologia- UO di Oncologia Medica Azienda
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana - Dipartimento Medico in Oncologia
city: Pordenone
country: Italy
facility: IRCCS CRO Aviano - SOC Oncologia medica e dei tumori Immunocorrelati - Dipartimento di Oncologia Pordenone S. Vito
city: Roma
country: Italy
facility: Pneumologia ad Indirizzo Oncologico 1 - A.O. San Camillo Forlanini
city: Roma
country: Italy
facility: Università la Sapienza - Policlinico Umberto I - Dipartimento di scienze radiologiche, oncologiche e anatomo-patologiche - UOC Oncologia B
city: Sassari
country: Italy
facility: UO Oncologia Medica - ASL N.1 di Sassari - Ospedale Civile di Sassari
city: Trento
country: Italy
facility: U.O. Oncologia Medica - Ospedale Santa Chiara
city: Udine
country: Italy
facility: Reparto di Oncologia - Azienda Sanitaria Universitaria Integrata di Udine - Presidio Ospedaliero Santa Maria della Misericordia
city: Verona
country: Italy
facility: U.S.O. GIVOP (Gruppo Interdisciplinare Veronese Oncologia Polmonare) Oncologia - Azienda Ospedaliera Integrata Verona
Study officials:
affiliation: Medical Oncology Unit - S.Orsola Malpighi University Hospital of Bologna
name: Andrea Ardizzoni, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical Oncology Unit - University Hospital of Parma
name: Marcello Tiseo, Dr
role: STUDY_CHAIR
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