Clinical trial NCT00982111: First-line Treatment of Patients With Stage IV Nonsquamous Non-Small Cell Lung Cancer With Necitumumab (IMC-11F8) and Pemetrexed-Cisplatin
Official title: A Randomized, Multicenter, Open-Label Phase 3 Study of Pemetrexed-Cisplatin Chemotherapy Plus Necitumumab (IMC-11F8) Versus Pemetrexed-Cisplatin Chemotherapy Alone in the First-Line Treatment of Patients With Stage IV Nonsquamous Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non Small Cell Lung Cancer
Keywords: Nonsquamous
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: Quintiles, Inc.
name: Parexel
name: PPD Development, LP
name: Medidata Solutions
name: Laboratory Corporation of America
name: University of Colorado, Denver
name: Thermo Fisher Scientific, Inc
name: Pacific Biomarkers
name: Intertek
name: Sysmex Inostics GmbH
First posted: 2009-09-22
Enrollment: 633
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 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 pemetrexed will be more effective in improving participant disease than the standard chemotherapy combination alone.

Detailed description: Multinational, randomized, multicenter, open-label Phase 3 study of 633 participants with advanced, nonsquamous (Stage IV) NSCLC. Participants will be randomized on a 1:1 basis to receive first-line necitumumab plus chemotherapy consisting of pemetrexed and cisplatin in study Arm A, or first-line pemetrexed-cisplatin chemotherapy alone in 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 (computed tomography or magnetic resonance imaging) of disease status 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 nonsquamous (adenocarcinoma/large cell or other) non small cell lung cancer
* Has Stage IV disease at the time of study entry
* Measurable or nonmeasurable disease (as defined by the Response Evaluation Criteria in Solid Tumors RECIST 1.0) at the time of study entry (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 an Eastern Cooperative Oncology Group performance status score of 0-2
* 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 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 participants 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

Exclusion Criteria:

* Has squamous non small cell lung cancer
* Has received prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the Epidermal Growth Factor Hormone (EGFR), vascular endothelial growth factor (VEGF), or VEGF receptor
* 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)
* Undergone major surgery or received any investigational therapy in the 4 weeks prior to randomization
* 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, potentially precluding protocol compliance
* Has 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 The participant has a known allergy / history of hypersensitivity reaction to any of the treatment components, including any ingredient used in the formulation of 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 31.6 Months)
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Randomization to Measured Progressive Disease or Death from Any Cause (Up to 30.4 Months)
measure: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Tumor Response Rate [ORR])
timeFrame: Baseline to Measured Progressive Disease (Up to 30.4 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 30.4 Months)
measure: Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab
timeFrame: Predose Day 1 of Cycle 2,3,4,5 and 6 Prior to Necitumumab Infusion, Up to 23 Weeks
measure: Number of Participants With Serum Anti-Necitumumab Antibody Assessment (Immunogenicity)
timeFrame: Baseline to Study Completion (Up to 31.6 Months)
measure: Mean Change From Baseline in Patient Reported Outcomes (PRO) Using the European Quality of Life-5 Dimensions (EQ-5D)
timeFrame: Baseline, Cycle 6 (Cycle = 3 weeks)
measure: Mean Change From Baseline in PRO as Measured Using the Lung Cancer Symptom Scale (LCSS)
timeFrame: Baseline, Cycle 6 (Cycle =3 Weeks)
measure: Epidermal Growth Factor Hormone (EGFR) Protein Expression Measured by Immunohistochemistry (IHC)
timeFrame: Baseline
measure: Percentage of Participants With EGFR Measured by IHC
timeFrame: Baseline
Other outcomes:
Locations:
city: Nyack
country: United States
facility: ImClone Investigational Site
state: New York
city: Kogarah
country: Australia
facility: ImClone Investigational Site
state: New South Wales
city: Hobart
country: Australia
facility: ImClone Investigational Site
state: Tasmania
city: East Bentleigh
country: Australia
facility: ImClone Investigational Site
state: Victoria
city: Rankweil
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: Liège
country: Belgium
facility: ImClone Investigational Site
city: Namur
country: Belgium
facility: ImClone Investigational Site
city: Barretos - SP
country: Brazil
facility: ImClone Investigational Site
city: Brasilia, Distrito Federal
country: Brazil
facility: ImClone Investigational Site
city: Goiania - GO
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: Ribeirão Preto - SP
country: Brazil
facility: ImClone Investigational Site
city: Salvador
country: Brazil
facility: ImClone Investigational Site
city: Santo Andre - SP
country: Brazil
facility: ImClone Investigational Site
city: São Paulo - SP
country: Brazil
facility: ImClone Investigational Site
city: Montreal
country: Canada
facility: ImClone Investigational Site
state: Quebec
city: Pula
country: Croatia
facility: ImClone Investigational Site
city: Caen
country: France
facility: ImClone Investigational Site
city: Paris
country: France
facility: ImClone Investigational Site
city: Berlin
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: 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: Mainz
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: 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: Budapest
country: Hungary
facility: ImClone Investigational Site
city: Budapest
country: Hungary
facility: ImClone Investigational Site
city: Deszk
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: Parma
country: Italy
facility: ImClone Investigational Site
city: Perugia
country: Italy
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: Szczecin
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: 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: 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: Omsk
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: Yaroslavi
country: Russian Federation
facility: ImClone Investigational Site
city: Bratislava
country: Slovakia
facility: ImClone Investigational Site
city: Nitra
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: Sevilla
country: Spain
facility: Imclone Investigational Site
state: Andalucia
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: L'Hospitalet de Llobregat
country: Spain
facility: ImClone Investigational Site
city: Aberdeen
country: United Kingdom
facility: ImClone Investigational Site
city: Bournemouth
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: Leeds
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: Paz-Ares L, Mezger J, Ciuleanu TE, Fischer JR, von Pawel J, Provencio M, Kazarnowicz A, Losonczy G, de Castro G Jr, Szczesna A, Crino L, Reck M, Ramlau R, Ulsperger E, Schumann C, Miziara JE, Lessa AE, Dediu M, Balint B, Depenbrock H, Soldatenkova V, Kurek R, Hirsch FR, Thatcher N, Socinski MA; INSPIRE investigators. Necitumumab plus pemetrexed and cisplatin as first-line therapy in patients with stage IV non-squamous non-small-cell lung cancer (INSPIRE): an open-label, randomised, controlled phase 3 study. Lancet Oncol. 2015 Mar;16(3):328-37. doi: 10.1016/S1470-2045(15)70046-X. Epub 2015 Feb 18.