Early Switch Maintenance vs Delayed Second-line Nivolumab in Advanced Stage Squamous Non-small Cell Lung Cancer (NSCLC) Patients (EDEN Trial) (EDEN)

September 30, 2022 updated by: Gruppo Oncologico Italiano di Ricerca Clinica

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

125

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Alessandria, Italy
        • SC Oncologia - ASO "SS Antonio e Biagio e Cesare Arrigo"
      • Bergamo, Italy
        • UO Oncologia Medica - A.S.S.T. Papa Giovanni XXIII di Bergamo
      • Bologna, Italy
        • UO di Oncologia Medica - Azienda Ospedaliero-Universitaria S. Orsola Malpighi
      • Bolzano, Italy
        • Divisione di Oncologia Medica - Ospedale di Bolzano
      • Brindisi, Italy
        • UOC Oncologia Medica - PO A.Perino ASL di Brindisi
      • Cremona, Italy
        • SC di Oncologia - Istituti Ospitalieri di Cremona
      • Cuneo, Italy
        • Dipartimento di Oncologia Medica - Azienda Ospedaliera S.Croce e Carle Cuneo - Ospedale Carle
      • Ferrara, Italy
        • UO di Oncologia Ematologia - Azienda Ospedaliero Universitaria di Ferrara
      • Firenze, Italy
        • S.C. Oncologia Medica 1 - Azienda Ospedaliero Universitaria Careggi
      • Genova, Italy
        • UOS Tumori Polmonari - IRCCS AOU San Martino -IST- Istituto Nazionale per la Ricerca sul Cancro
      • Lucca, Italy
        • Azienda USL Toscana nord ovest - Ospedale San Luca di Lucca - Dipartimento Oncologico
      • Modena, Italy
        • Azienda Ospedaliero-Universitaria di Modena - Policlinico - Dipartimento di Scienze Mediche e Chirurgiche, Materno Infantili e dell'adulto
      • Monza, Italy
        • SC di Oncologia Medica - A.O. San Gerardo
      • Napoli, Italy
        • U.O.C Pneumologia ad Indirizzo Oncologico - AORN Ospedali dei Colli Monaldi
      • Padova, Italy
        • IOV Istituto Oncologico Veneto - UOC di Oncologia Medica 2
      • Parma, Italy
        • UOC di Oncologia Medica - Azienda Ospedaliero Universitaria di Parma
      • Perugia, Italy
        • S.C. di Oncologia Medica - Ospedale S.Maria della Misericordia
      • Piacenza, Italy
        • AUSL - Piacenza - Ospedale "Guglielmo da Saliceto"-Dip.Oncologia e Ematologia- UO di Oncologia Medica Azienda
      • Pisa, Italy
        • Azienda Ospedaliera Universitaria Pisana - Dipartimento Medico in Oncologia
      • Pordenone, Italy, 33170
        • IRCCS CRO Aviano - SOC Oncologia medica e dei tumori Immunocorrelati - Dipartimento di Oncologia Pordenone S. Vito
      • Roma, Italy
        • Pneumologia ad Indirizzo Oncologico 1 - A.O. San Camillo Forlanini
      • Roma, Italy
        • Università la Sapienza - Policlinico Umberto I - Dipartimento di scienze radiologiche, oncologiche e anatomo-patologiche - UOC Oncologia B
      • Sassari, Italy
        • UO Oncologia Medica - ASL N.1 di Sassari - Ospedale Civile di Sassari
      • Trento, Italy
        • U.O. Oncologia Medica - Ospedale Santa Chiara
      • Udine, Italy
        • Reparto di Oncologia - Azienda Sanitaria Universitaria Integrata di Udine - Presidio Ospedaliero Santa Maria della Misericordia
      • Verona, Italy
        • U.S.O. GIVOP (Gruppo Interdisciplinare Veronese Oncologia Polmonare) Oncologia - Azienda Ospedaliera Integrata Verona
    • Bologna
      • Imola, Bologna, Italy
        • UOC Oncologia - Azienda USL di Imola - Ospedale Santa Maria della Scaletta
    • Forlì
      • Meldola, Forlì, Italy
        • Oncologia Medica - IRST - IRCCS di Meldola
    • Lucca
      • Lido Di Camaiore, Lucca, Italy
        • AUSL 12 Viareggio, Ospedale Versilia, Lido di Camaiore (LU) - Oncologia Medica
    • Modena
      • Carpi, Modena, Italy
        • UO Medicina Oncologica - Ospedale di Carpi (MO) - Azienda USL di Modena
    • Varese
      • Saronno, Varese, Italy
        • UOC di Oncologia Medica - ASST Valle Olona - Presidio Ospedaliero di Saronno

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A_Nivolumab
Nivolumab 240 mg IV every 2 weeks until disease progression, unacceptable toxicity, patient refusal or Investigator's decision
Drug: Nivolumab 10 MG/ML Intravenous Solution
240 mg as a 30 minutes IV infusion on Day 1 of each treatment cycle every 2 weeks, until intolerable toxicity or patient refusal or investigator's decision. In case of disease progression the treatment should be discontinued unless documented clinical benefits in the Investigator's judgement (no rapid progression, tolerance of trial drug, stable performance status, treatment maintenance does not delay an imminent intervention to prevent serious complication of PD) and no evidence of further progression at a radiographic assessment performed within 6 weeks. No dose escalations or reduction allowed. Administration delay until 6 weeks as well as resuming dose are allowed according to protocol defined criteria.
Other: B_Best Supportive Care
Best Supportive Care until disease progression followed by Nivolumab at a dose of 240 mg IV until further disease progression, unacceptable toxicity, patient refusal or Investigator's decision.
Drug: Nivolumab 10 MG/ML Intravenous Solution
240 mg as a 30 minutes IV infusion on Day 1 of each treatment cycle every 2 weeks, until intolerable toxicity or patient refusal or investigator's decision. In case of disease progression the treatment should be discontinued unless documented clinical benefits in the Investigator's judgement (no rapid progression, tolerance of trial drug, stable performance status, treatment maintenance does not delay an imminent intervention to prevent serious complication of PD) and no evidence of further progression at a radiographic assessment performed within 6 weeks. No dose escalations or reduction allowed. Administration delay until 6 weeks as well as resuming dose are allowed according to protocol defined criteria.
Other: Best Supportive Care
Care that aims to optimize the comfort, function and social support of the patients and their family at all stages of the illness. Best Supportive Care (BSC)includes the use of analgesics, antibiotics, blood tranfusions, blood products, radiotherapy, corticosteroids, antiemetics, antidiarrheals, vitamins and any intervention aiming the improvement of patient's discomfort. Any chemotherapy, immunotherapy and targeted therapy are not considered as part of BSC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: 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 .
Time from randomization to death date. Please note: a subject who has not died will be censored at the last known date alive.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: 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.
Time from randomization to the date of the first documented tumor progression (RECIST 1.1) or death due to any cause. Please note: clinical deterioration not radiologically confirmed is not considered progression for the purpose of this measure. Subjects who did not have any study tumor assessments and did not die will be censored on the date they were randomized. Subjects who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last evaluable tumor assessment prior to the initiation od the subsequent anti-cancer therapy.
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.
Progression-Free Survival from induction (PFSind)
Time Frame: 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.
Time from first chemotherapy cycle until documented tumor progression or death by any cause.
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.
Time to Treatment Failure (TTF)
Time Frame: 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.
Time from randomization to treatment discontinuation for any reason, including disease progression, treatment toxicity, patients preference, Investigator's decision or death.
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.
Overall Survival from Induction (OSind)
Time Frame: 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..
Time from first chemotherapy cycle until death by any cause
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..

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gruppo Oncologico Italiano di Ricerca Clinica

Collaborators

Bioikos Ambiente Srl
Istituto Toscano Tumori
Temas srl
Mipharm S.p.A.
Bristol Myers Squibb Srl Italia

Investigators

  • Principal Investigator: Andrea Ardizzoni, Dr, Medical Oncology Unit - S.Orsola Malpighi University Hospital of Bologna
  • Study Chair: Marcello Tiseo, Dr, Medical Oncology Unit - University Hospital of Parma

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 25, 2017

Primary Completion (Anticipated)

January 31, 2023

Study Completion (Anticipated)

January 31, 2023

Study Registration Dates

First Submitted

March 5, 2018

First Submitted That Met QC Criteria

May 30, 2018

First Posted (Actual)

May 31, 2018

Study Record Updates

Last Update Posted (Actual)

October 3, 2022

Last Update Submitted That Met QC Criteria

September 30, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GOIRC-04-2016

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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