Clinical trial NCT00981058: First-line Treatment of Participants With Stage IV Squamous Non-Small Cell Lung Cancer With Necitumumab and Gemcitabine-Cisplatin
Official title: A Randomized, Multicenter, Open-Label Phase 3 Study of Gemcitabine-Cisplatin Chemotherapy Plus Necitumumab (IMC-11F8) Versus Gemcitabine-Cisplatin Chemotherapy Alone in the First-Line Treatment of Patients With Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non Small Cell Lung Cancer
Keywords: Squamous
Non Small Cell Lung Cancer
First line treatment
Monoclonal
Antibodies
Epidermal Growth Factor Receptor (EGFR)
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Parexel
name: PPD Development, LP
name: Medidata Solutions
name: Laboratory Corporation of America
name: University of Colorado, Denver
name: Thermo Fisher Scientific FS
name: ICON Clinical Research
name: Pacific Biomarkers
name: Sysmex Inostics GmbH
name: Intertek
First posted: 2009-09-22
Enrollment: 1093
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: The research study is testing the investigational drug necitumumab (IMC-11F8) in the treatment of advanced non-small cell lung cancer. The aim of this study is to determine if necitumumab, given together with a standard chemotherapy combination consisting of cisplatin and gemcitabine will be more effective in improving participant disease than the standard chemotherapy combination alone.

Detailed description: Multinational, randomized, multicenter, open-label, Phase III study of 1093 participants (age ≥ 18 years) with histologically- or cytologically-confirmed, stage IV squamous-cell NSCLC, who have received no prior therapy for metastatic disease, will be randomized on a 1:1 basis to receive first-line necitumumab plus chemotherapy consisting of gemcitabine and cisplatin in study Arm A, or gemcitabine-cisplatin chemotherapy alone in study Arm B. Baseline radiographic assessment of disease will be performed within 21 days prior to randomization (first treatment will be administered within 7 days following randomization). Participants will undergo radiographic assessment of disease status (computed tomography or magnetic resonance imaging) every 6 weeks (± 3 days), until there is radiographic documentation of progressive disease (PD). Chemotherapy will continue for a maximum of six cycles in each arm (or until there is radiographic documentation of PD, toxicity requiring cessation, protocol noncompliance or withdrawal of consent); participants in Arm A only will continue to receive necitumumab until there is radiographic documentation of PD, toxicity requiring cessation, protocol noncompliance, or withdrawal of consent.

After the end-of-study-visit (following PD), follow-up information regarding further anticancer treatment and survival will be collected every 2 months (± 7 days). For participants who discontinue study for reasons other than PD (eg, symptomatic deterioration), information on disease progression will also be collected until PD is documented. Follow-up will continue as long as the participant is alive, or until the end of the trial.

Eligibility criteria: Inclusion Criteria:

* Has histologically or cytologically confirmed squamous NSCLC
* Has Stage IV disease at the time of study entry
* Measurable or nonmeasurable disease at the time of study entry as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) (participants with only truly nonmeasurable disease are not eligible)
* Has resolution to Grade ≤ 1 of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (with the exception of alopecia)
* Has adequate hepatic function
* Has adequate renal function
* Has adequate hematologic function
* If female, is surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method (failure rate \< 1%) during and for 6 months after the treatment period (oral hormonal contraception alone is not considered highly effective and must be used in combination with a barrier method)
* If male, the participant is surgically sterile or compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period
* Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization
* Has archived tumor tissue available for analysis of EGFR and KRAS mutation status (by PCR) and EGFR gene copy number (by FISH); minimum of four slides, paraffin-embedded tissue, required

Exclusion Criteria:

* Has nonsquamous NSCLC (adenocarcinoma/large cell or other)
* Has received prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the EGFR, vascular endothelial growth factor (VEGF), or VEGF receptor
* Has received previous chemotherapy for advanced NSCLC (participants who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 1 year prior to randomization)
* Has undergone major surgery or received any investigational therapy in the 4 weeks prior to randomization
* Has undergone chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions, which is allowed)
* Has brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants. Participants who have undergone previous radiotherapy for brain metastases, who are now nonsymptomatic and no longer require treatment with steroids or anticonvulsants, are eligible
* Has superior vena cava syndrome contraindicating hydration
* Has current clinically-relevant coronary artery disease or uncontrolled congestive heart failure
* Has experienced myocardial infarction within 6 months prior to randomization
* Has an ongoing or active infection (requiring antibiotics), including active tuberculosis or known infection with the human immunodeficiency virus
* Has a history of significant neurological or psychiatric disorders, including dementia, seizures, or bipolar disorder
* Has any National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0 Grade ≥ 2 peripheral neuropathy
* Has significant third space fluid retention, requiring repeated drainage
* Has any other serious uncontrolled medical disorders or psychological conditions that would, in the opinion of the investigator, limit the participant's ability to complete the study or sign an informed consent document
* Has a known allergy / history of hypersensitivity reaction to any of the treatment components, including any ingredient used in the formulation of necitumumab (IMC-11F8), or any other contraindication to one of the administered treatments
* Is pregnant or breastfeeding
* Has a known history of drug abuse
* Has a concurrent active malignancy other than adequately-treated basal cell carcinoma of the skin or preinvasive carcinoma of the cervix. A participant with previous history of malignancy other than NSCLC is eligible, provided that he/she has been free of disease for ≥ 3 years

Primary outcomes:
measure: Overall Survival Time (OS)
timeFrame: Randomization to Death from Any Cause (Up to 31 Months)
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Randomization to Measured Progressive Disease or Death from Any Cause (Up to 31 Months)
measure: Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) (Objective Response Rate [ORR])
timeFrame: Baseline to Measured Progressive Disease (Up to 31 Months)
measure: Time to Treatment Failure (TTF)
timeFrame: Randomization to Measured Progressive Disease, Death From Any Cause, Discontinuation of Treatment or Initiation of New Anticancer Therapy (Up to 31 Months)
measure: Mean Change From Baseline in Patient Reported Outcomes (PRO) Using the European Quality of Life-5 Dimension (EQ-5D)
timeFrame: Baseline, Cycle 6 (Cycle = 3 Weeks)
measure: Mean Change From Baseline in PRO Using the Outcomes Lung Cancer Symptom Scale (LCSS)
timeFrame: Baseline, Cycle 6 (Cycle = 3 Weeks)
measure: Number of Participants With an Epidermal Growth Factor Hormone (EGFR) Protein Expression Measured by Immunohistochemistry (IHC)
timeFrame: 31 Months
measure: Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab
timeFrame: Day 1 of Cycle 2, 3, 4, 5 and 6 Prior to Necitumumab Drug Infusion, Up to 24 Months
measure: Number of Participants With a Serum Anti-Necitumumab Antibody Assessment
timeFrame: Baseline through 31 Months
Other outcomes:
Locations:
city: Chandler
country: United States
facility: ImClone Investigational Site
state: Arizona
city: Fayetteville
country: United States
facility: ImClone Investigational Site
state: Arkansas
city: Sacramento
country: United States
facility: ImClone Investigational Site
state: California
city: Galesburg
country: United States
facility: ImClone Investigational Site
state: Illinois
city: Goshen
country: United States
facility: ImClone Investigational Site
state: Indiana
city: Wichita
country: United States
facility: ImClone Investigational Site
state: Kansas
city: Hazard
country: United States
facility: ImClone Investigational Site
state: Kentucky
city: Baltimore
country: United States
facility: ImClone Investigational Site
state: Maryland
city: Jefferson City
country: United States
facility: ImClone Investigational Site
state: Missouri
city: Lincoln
country: United States
facility: ImClone Investigational Site
state: Nebraska
city: New York
country: United States
facility: ImClone Investigational Site
state: New York
city: Akron
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Camp Hill
country: United States
facility: ImClone Investigational Site
state: Pennsylvania
city: Memphis
country: United States
facility: ImClone Investigational Site
state: Tennessee
city: Fairfax
country: United States
facility: ImClone Investigational Site
state: Virginia
city: Garran
country: Australia
facility: ImClone Investigational Site
state: New South Wales
city: Westmead
country: Australia
facility: ImClone Investigational Site
state: New South Wales
city: Wollongong
country: Australia
facility: ImClone Investigational Site
state: New South Wales
city: East Bentleigh
country: Australia
facility: ImClone Investigational Site
state: Victoria
city: Geelong
country: Australia
facility: ImClone Investigational Site
state: Victoria
city: Linz
country: Austria
facility: ImClone Investigational Site
city: Wien
country: Austria
facility: ImClone Investigational Site
city: Wien
country: Austria
facility: ImClone Investigational Site
city: Duffel
country: Belgium
facility: ImClone Investigational Site
city: Liege
country: Belgium
facility: ImClone Investigational Site
city: Namur
country: Belgium
facility: ImClone Investigational Site
city: Barretos
country: Brazil
facility: ImClone Investigational Site
city: Brasilia, Distrito Federal
country: Brazil
facility: ImClone Investigational Site
city: Goiania
country: Brazil
facility: ImClone Investigational Site
city: Ijui
country: Brazil
facility: ImClone Investigational Site
city: Itajai
country: Brazil
facility: ImClone Investigational Site
city: Lajeado
country: Brazil
facility: ImClone Investigational Site
city: Porto Alegre/RS
country: Brazil
facility: ImClone Investigational Site
city: Salvador
country: Brazil
facility: ImClone Investigational Site
city: Santo Andre
country: Brazil
facility: ImClone Investigational Site
city: Sao Paulo
country: Brazil
facility: ImClone Investigational Site
city: São Paulo - SP
country: Brazil
facility: ImClone Investigational Site
city: Saint John
country: Canada
facility: ImClone Investigational Site
state: New Brunswick
city: Brampton
country: Canada
facility: ImClone Investigational Site
state: Ontario
city: Saskatoon
country: Canada
facility: ImClone Investigational Site
state: Saskatchewan
city: Dubrovnik
country: Croatia
facility: ImClone Investigational Site
city: Pula
country: Croatia
facility: ImClone Investigational Site
city: Zagreb
country: Croatia
facility: ImClone Investigational site
city: Brest Cedex
country: France
facility: ImClone Investigational Site
city: Caen
country: France
facility: ImClone Investigational Site
city: Draguignan
country: France
facility: ImClone Investigational Site
city: Grenoble
country: France
facility: ImClone Investigational Site
city: Le Mans Cedex
country: France
facility: ImClone Investigational Site
city: Le Mans
country: France
facility: ImClone Investigational Site
city: Lille
country: France
facility: ImClone Investigational Site
city: Lyon
country: France
facility: ImClone Investigational Site
city: Marseille
country: France
facility: ImClone Investigational Site
city: Paris
country: France
facility: ImClone Investigational Site
city: Paris
country: France
facility: ImClone Investigational Site
city: Paris
country: France
facility: ImClone Investigational Site
city: Paris
country: France
facility: ImClone Investigational Site
city: Rennes
country: France
facility: ImClone Investigational Site
city: Saint-Jean
country: France
facility: ImClone Investigational Site
city: Toulon Armées
country: France
facility: ImClone Investigational Site
city: Berlin
country: Germany
facility: ImClone Investigational Site
city: Essen
country: Germany
facility: ImClone Investigational Site
city: Essen
country: Germany
facility: ImClone Investigational Site
city: Frankfurt
country: Germany
facility: ImClone Investigational Site
city: Gauting
country: Germany
facility: ImClone Investigational Site
city: Großhansdorf
country: Germany
facility: ImClone Investigational Site
city: Halle
country: Germany
facility: ImClone Investigational Site
city: Hamburg
country: Germany
facility: ImClone Investigational Site
city: Hamburg
country: Germany
facility: ImClone Investigational Site
city: Heidelberg
country: Germany
facility: ImClone Investigational Site
city: Hemer
country: Germany
facility: ImClone Investigational Site
city: Hofheim
country: Germany
facility: ImClone Investigational Site
city: Karlsruhe
country: Germany
facility: ImClone Investigational Site
city: Lostau
country: Germany
facility: ImClone Investigational Site
city: Löwenstein
country: Germany
facility: ImClone Investigational Site
city: München
country: Germany
facility: ImClone Investigational Site
city: Münster
country: Germany
facility: ImClone Investigational Site
city: Regensburg
country: Germany
facility: ImClone Investigational Site
city: Regensburg
country: Germany
facility: ImClone Investigational Site
city: Ulm
country: Germany
facility: ImClone Investigational Site
city: Athens
country: Greece
facility: ImClone Investigational Site
city: Heraklion, Crete
country: Greece
facility: ImClone Investigational Site
city: Patras
country: Greece
facility: ImClone Investigational Site
city: Thessaloniki
country: Greece
facility: ImClone Investigational Site
city: Budapest
country: Hungary
facility: ImClone Investigational Site
city: Budapest
country: Hungary
facility: ImClone Investigational Site
city: Deszk
country: Hungary
facility: ImClone Investigational Site
city: Farkasgyepü
country: Hungary
facility: ImClone Investigational Site
city: Mosonmagyaróvár
country: Hungary
facility: ImClone Investigational Site
city: Szombathely
country: Hungary
facility: ImClone Investigational Site
city: Székesfehérvár
country: Hungary
facility: ImClone Investigational Site
city: Törökbálint
country: Hungary
facility: ImClone Investigational Site
city: Lido di Camaiore
country: Italy
facility: ImClone Investigational Site
state: Lucca
city: Aviano
country: Italy
facility: ImClone Investigational Site
state: Pordenone
city: Frosinone
country: Italy
facility: ImClone Investigational Site
city: Genova
country: Italy
facility: ImClone Investigational Site
city: Milano
country: Italy
facility: ImClone Investigational Site
city: Milano
country: Italy
facility: ImClone Investigational Site
city: Monza
country: Italy
facility: ImClone Investigational Site
city: Parma
country: Italy
facility: ImClone Investigational Site
city: Perugia
country: Italy
facility: ImClone Investigational Site
city: Incheon
country: Korea, Republic of
facility: ImClone Investigational Site
city: Jeonju-si
country: Korea, Republic of
facility: ImClone Investigational Site
city: Seongnam
country: Korea, Republic of
facility: ImClone Investigational Site
city: Seoul
country: Korea, Republic of
facility: ImClone Investigational Site
city: Seoul
country: Korea, Republic of
facility: ImClone Investigational Site
city: Seoul
country: Korea, Republic of
facility: ImClone Investigational Site
city: Suwon
country: Korea, Republic of
facility: ImClone Investigational Site
city: Cebu City
country: Philippines
facility: ImClone Investigational Site
city: Cebu
country: Philippines
facility: ImClone Investigational Site
city: Davao City
country: Philippines
facility: ImClone Investigational Site
city: Makati City
country: Philippines
facility: ImClone Investigational Site
city: Manila
country: Philippines
facility: ImClone Investigational Site
city: Quezon City
country: Philippines
facility: ImClone Investigational Site
city: Quezon City
country: Philippines
facility: ImClone Investigational Site
city: Olsztyn
country: Poland
facility: ImClone Investigational Site
city: Otwock
country: Poland
facility: ImClone Investigational Site
city: Poznan
country: Poland
facility: ImClone Investigational Site
city: Radom
country: Poland
facility: ImClone Investigational Site
city: Rzeszow
country: Poland
facility: ImClone Investigational Site
city: Szczecin
country: Poland
facility: ImClone Investigational Site
city: Torun
country: Poland
facility: ImClone Investigational Site
city: Wroclaw
country: Poland
facility: ImClone Investigational Site
city: Coimbra
country: Portugal
facility: ImClone Investigational Site
city: Lisboa
country: Portugal
facility: ImClone Investigational Site
city: Lisboa
country: Portugal
facility: ImClone Investigational Site
city: Porto
country: Portugal
facility: ImClone Investigational Site
city: Brasov
country: Romania
facility: ImClone Investigational Site
city: Bucharest
country: Romania
facility: ImClone Investigational Site
city: Bucharest
country: Romania
facility: ImClone Investigational Site
city: Cluj-Napoca
country: Romania
facility: ImClone Investigational Site
city: Craiova, Dolj
country: Romania
facility: ImClone Investigational Site
city: Iasi
country: Romania
facility: ImClone Investigational Site
city: Piatra Neamt
country: Romania
facility: ImClone Investigational Site
city: Sibiu
country: Romania
facility: ImClone Investigational Site
city: Ivanovo
country: Russian Federation
facility: ImClone Investigational Site
city: Kirov
country: Russian Federation
facility: ImClone Investigational Site
city: Krasnodar
country: Russian Federation
facility: ImClone Investigational Site
city: Moscow
country: Russian Federation
facility: ImClone Investigational Site
city: Omsk
country: Russian Federation
facility: ImClone Investigational Site
city: Smolensk
country: Russian Federation
facility: ImClone Investigational Site
city: St. Petersburg
country: Russian Federation
facility: ImClone Investigational Site
city: St. Petersburg
country: Russian Federation
facility: ImClone Investigational Site
city: St. Petersburg
country: Russian Federation
facility: ImClone Investigational Site
city: St. Petersburg
country: Russian Federation
facility: ImClone Investigational Site
city: Ufa
country: Russian Federation
facility: ImClone Investigational Site
city: Yaroslavl
country: Russian Federation
facility: ImClone Investigational Site
city: Belgrade
country: Serbia
facility: ImClone Investigational Site
city: Kragujevac
country: Serbia
facility: ImClone Investigational Site
city: Nis
country: Serbia
facility: ImClone Investigational Site
city: Sremska Kamenica
country: Serbia
facility: ImClone Investigational Site
city: Singapore
country: Singapore
facility: ImClone Investigational Site
city: Bratislava
country: Slovakia
facility: ImClone Investigational Site
city: Nitra
country: Slovakia
facility: ImClone Investigational Site
city: Poprad
country: Slovakia
facility: ImClone Investigational Site
city: Bloemfontein
country: South Africa
facility: ImClone Investigational Site
state: Free State
city: Pretoria
country: South Africa
facility: ImClone Investigational Site
state: Gauteng
city: Durban
country: South Africa
facility: ImClone Investigational Site
state: Kwazulu-Natal
city: Sevilla
country: Spain
facility: ImClone Investigational Site
state: Andalucía
city: Avila
country: Spain
facility: ImClone Investigational Site
state: Castilla Y Leon
city: Barcelona
country: Spain
facility: ImClone Investigational Site
state: Cataluña
city: Barcelona
country: Spain
facility: ImClone Investigational Site
state: Cataluña
city: Terrassa
country: Spain
facility: ImClone Investigational Site
state: Cataluña
city: Madrid
country: Spain
facility: ImClone Investigational Site
state: Communidad De Madrid
city: Madrid
country: Spain
facility: ImClone Investigational Site
state: Communidad De Madrid
city: Majadahonda
country: Spain
facility: ImClone Investigational Site
state: Communidad De Madrid
city: Barcelona
country: Spain
facility: ImClone Investigational Site
city: L'Hospitalet de Llobregat
country: Spain
facility: ImClone Investigational Site
city: Madrid
country: Spain
facility: ImClone Investigational Site
city: Taichung
country: Taiwan
facility: ImClone Investigational Site
city: Taichung
country: Taiwan
facility: ImClone Investigational Site
city: Chiang Mai
country: Thailand
facility: ImClone Investigational Site
city: Songkhla
country: Thailand
facility: ImClone Investigational Site
city: Aberdeen
country: United Kingdom
facility: ImClone Investigational Site
city: Bournemouth
country: United Kingdom
facility: ImClone Investigational Site
city: Dundee
country: United Kingdom
facility: ImClone Investigational Site
city: Edinburgh
country: United Kingdom
facility: ImClone Investigational Site
city: Guildford
country: United Kingdom
facility: ImClone Investigational Site
city: Liverpool
country: United Kingdom
facility: ImClone Investigational Site
city: London
country: United Kingdom
facility: ImClone Investigational Site
city: Manchester
country: United Kingdom
facility: ImClone Investigational Site
city: Manchester
country: United Kingdom
facility: ImClone Investigational Site
city: Preston
country: United Kingdom
facility: ImClone Investigational Site
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Ciuleanu T, Socinski MA, Obasaju C, Luft AV, Szczesna A, Szafranski W, Ramlau R, Balint B, Molinier O, Depenbrock H, Nanda S, Paz-Ares L, Thatcher N. Efficacy and Safety of Necitumumab Continuation Therapy in the Phase III SQUIRE Study of Patients With Stage IV Squamous Non-Small-Cell Lung Cancer. Clin Lung Cancer. 2018 Mar;19(2):130-138.e2. doi: 10.1016/j.cllc.2017.10.004. Epub 2017 Oct 13.
citation: Paz-Ares L, Socinski MA, Shahidi J, Hozak RR, Soldatenkova V, Kurek R, Varella-Garcia M, Thatcher N, Hirsch FR. Correlation of EGFR-expression with safety and efficacy outcomes in SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin plus necitumumab versus gemcitabine-cisplatin alone in the first-line treatment of patients with stage IV squamous non-small-cell lung cancer. Ann Oncol. 2016 Aug;27(8):1573-9. doi: 10.1093/annonc/mdw214. Epub 2016 May 20.
citation: Reck M, Socinski MA, Luft A, Szczesna A, Dediu M, Ramlau R, Losonczy G, Molinier O, Schumann C, Gralla RJ, Bonomi P, Brown J, Soldatenkova V, Chouaki N, Obasaju C, Peterson P, Thatcher N. The Effect of Necitumumab in Combination with Gemcitabine plus Cisplatin on Tolerability and on Quality of Life: Results from the Phase 3 SQUIRE Trial. J Thorac Oncol. 2016 Jun;11(6):808-18. doi: 10.1016/j.jtho.2016.03.002. Epub 2016 Mar 12.
citation: Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Balint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA; SQUIRE Investigators. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015 Jul;16(7):763-74. doi: 10.1016/S1470-2045(15)00021-2. Epub 2015 Jun 1.