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

NCT03542461 | Unknown Phase 3

• 1 other identifier: GOIRC-04-2016
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 31

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.

Conditions

Squamous Non-small Cell Lung Cancer

Keywords

Squamous NSCLC; Nivolumab

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  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 Outcomes (4)

• Progression-Free Survival (PFS)

  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)

  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)

  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)

  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..

Study Arms (2)

A_Nivolumab

EXPERIMENTAL

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

B_Best Supportive Care

OTHER

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; Other: Best Supportive Care

Interventions

Nivolumab 10 MG/ML Intravenous Solution DRUG

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.

A_Nivolumab; B_Best Supportive Care

Best Supportive Care OTHER

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.

B_Best Supportive Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Gruppo Oncologico Italiano di Ricerca Clinica: lead
• Mipharm S.p.A.: collaborator
• Bioikos Ambiente Srl: collaborator
• Istituto Toscano Tumori: collaborator
• Temas srl: collaborator
• Bristol Myers Squibb Srl Italia: collaborator

Study Sites (31)

UOC Oncologia - Azienda USL di Imola - Ospedale Santa Maria della Scaletta

Imola, Bologna, Italy

Location

Oncologia Medica - IRST - IRCCS di Meldola

Meldola, Forlì, Italy

Location

AUSL 12 Viareggio, Ospedale Versilia, Lido di Camaiore (LU) - Oncologia Medica

Lido di Camaiore, Lucca, Italy

Location

UO Medicina Oncologica - Ospedale di Carpi (MO) - Azienda USL di Modena

Carpi, Modena, Italy

Location

UOC di Oncologia Medica - ASST Valle Olona - Presidio Ospedaliero di Saronno

Saronno, Varese, Italy

Location

SC Oncologia - ASO "SS Antonio e Biagio e Cesare Arrigo"

Alessandria, Italy

Location

UO Oncologia Medica - A.S.S.T. Papa Giovanni XXIII di Bergamo

Bergamo, Italy

Location

UO di Oncologia Medica - Azienda Ospedaliero-Universitaria S. Orsola Malpighi

Bologna, Italy

Location

Divisione di Oncologia Medica - Ospedale di Bolzano

Bolzano, Italy

Location

UOC Oncologia Medica - PO A.Perino ASL di Brindisi

Brindisi, Italy

Location

SC di Oncologia - Istituti Ospitalieri di Cremona

Cremona, Italy

Location

Dipartimento di Oncologia Medica - Azienda Ospedaliera S.Croce e Carle Cuneo - Ospedale Carle

Cuneo, Italy

Location

UO di Oncologia Ematologia - Azienda Ospedaliero Universitaria di Ferrara

Ferrara, Italy

Location

S.C. Oncologia Medica 1 - Azienda Ospedaliero Universitaria Careggi

Florence, Italy

Location

UOS Tumori Polmonari - IRCCS AOU San Martino -IST- Istituto Nazionale per la Ricerca sul Cancro

Genova, Italy

Location

Azienda USL Toscana nord ovest - Ospedale San Luca di Lucca - Dipartimento Oncologico

Lucca, Italy

Location

Azienda Ospedaliero-Universitaria di Modena - Policlinico - Dipartimento di Scienze Mediche e Chirurgiche, Materno Infantili e dell'adulto

Modena, Italy

Location

SC di Oncologia Medica - A.O. San Gerardo

Monza, Italy

Location

U.O.C Pneumologia ad Indirizzo Oncologico - AORN Ospedali dei Colli Monaldi

Napoli, Italy

Location

IOV Istituto Oncologico Veneto - UOC di Oncologia Medica 2

Padua, Italy

Location

UOC di Oncologia Medica - Azienda Ospedaliero Universitaria di Parma

Parma, Italy

Location

S.C. di Oncologia Medica - Ospedale S.Maria della Misericordia

Perugia, Italy

Location

AUSL - Piacenza - Ospedale "Guglielmo da Saliceto"-Dip.Oncologia e Ematologia- UO di Oncologia Medica Azienda

Piacenza, Italy

Location

Azienda Ospedaliera Universitaria Pisana - Dipartimento Medico in Oncologia

Pisa, Italy

Location

IRCCS CRO Aviano - SOC Oncologia medica e dei tumori Immunocorrelati - Dipartimento di Oncologia Pordenone S. Vito

Pordenone, 33170, Italy

Location

Pneumologia ad Indirizzo Oncologico 1 - A.O. San Camillo Forlanini

Roma, Italy

Location

Università la Sapienza - Policlinico Umberto I - Dipartimento di scienze radiologiche, oncologiche e anatomo-patologiche - UOC Oncologia B

Roma, Italy

Location

UO Oncologia Medica - ASL N.1 di Sassari - Ospedale Civile di Sassari

Sassari, Italy

Location

U.O. Oncologia Medica - Ospedale Santa Chiara

Trento, Italy

Location

Reparto di Oncologia - Azienda Sanitaria Universitaria Integrata di Udine - Presidio Ospedaliero Santa Maria della Misericordia

Udine, Italy

Location

U.S.O. GIVOP (Gruppo Interdisciplinare Veronese Oncologia Polmonare) Oncologia - Azienda Ospedaliera Integrata Verona

Verona, Italy

Location

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MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Andrea Ardizzoni, Dr

  Medical Oncology Unit - S.Orsola Malpighi University Hospital of Bologna

  PRINCIPAL INVESTIGATOR

• Marcello Tiseo, Dr

  Medical Oncology Unit - University Hospital of Parma

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: March 5, 2018
• First Posted: May 31, 2018
• Study Start: September 25, 2017
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: October 3, 2022

Record last verified: 2022-09

Locations

IT (31)