First-line Treatment of Participants With Stage IV Squamous Non-Small Cell Lung Cancer With Necitumumab and Gemcitabine-Cisplatin

Non Small Cell Lung Cancer Clinical Trial

— SQUIRE  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00981058
• Other study ID #: 13909
• Secondary ID: CP11-0806I4X-IE-
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 7, 2010
• Est. completion date: June 2024

Study information

• Verified date: March 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1093
• Est. completion date: June 2024
• Est. primary completion date: June 17, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Biological:
• Necitumumab
800 milligrams (mg) Intravenously IV infusion on Days 1 and 8 of every 3 week cycle. Continues until progressive disease, toxicity, noncompliance, or withdrawal.

Drug:
• Gemcitabine
1250 mg/m2 on Days 1 and 8 of every 3 week cycle. Continues for a maximum of six cycles.
• Cisplatin
75 mg/m2 IV on Day 1 of every 3 week cycle. Continues for a maximum of six cycles.

Locations

Country	Name	City	State
Australia	ImClone Investigational Site	East Bentleigh	Victoria
Australia	ImClone Investigational Site	Garran	New South Wales
Australia	ImClone Investigational Site	Geelong	Victoria
Australia	ImClone Investigational Site	Westmead	New South Wales
Australia	ImClone Investigational Site	Wollongong	New South Wales
Austria	ImClone Investigational Site	Linz
Austria	ImClone Investigational Site	Wien
Austria	ImClone Investigational Site	Wien
Belgium	ImClone Investigational Site	Duffel
Belgium	ImClone Investigational Site	Liege
Belgium	ImClone Investigational Site	Namur
Brazil	ImClone Investigational Site	Barretos
Brazil	ImClone Investigational Site	Brasilia, Distrito Federal
Brazil	ImClone Investigational Site	Goiania
Brazil	ImClone Investigational Site	Ijui
Brazil	ImClone Investigational Site	Itajai
Brazil	ImClone Investigational Site	Lajeado
Brazil	ImClone Investigational Site	Porto Alegre/RS
Brazil	ImClone Investigational Site	Salvador
Brazil	ImClone Investigational Site	Santo Andre
Brazil	ImClone Investigational Site	Sao Paulo
Brazil	ImClone Investigational Site	São Paulo - SP
Canada	ImClone Investigational Site	Brampton	Ontario
Canada	ImClone Investigational Site	Saint John	New Brunswick
Canada	ImClone Investigational Site	Saskatoon	Saskatchewan
Croatia	ImClone Investigational Site	Dubrovnik
Croatia	ImClone Investigational Site	Pula
Croatia	ImClone Investigational site	Zagreb
France	ImClone Investigational Site	Brest Cedex
France	ImClone Investigational Site	Caen
France	ImClone Investigational Site	Draguignan
France	ImClone Investigational Site	Grenoble
France	ImClone Investigational Site	Le Mans
France	ImClone Investigational Site	Le Mans Cedex
France	ImClone Investigational Site	Lille
France	ImClone Investigational Site	Lyon
France	ImClone Investigational Site	Marseille
France	ImClone Investigational Site	Paris
France	ImClone Investigational Site	Paris
France	ImClone Investigational Site	Paris
France	ImClone Investigational Site	Paris
France	ImClone Investigational Site	Rennes
France	ImClone Investigational Site	Saint-Jean
France	ImClone Investigational Site	Toulon Armées
Germany	ImClone Investigational Site	Berlin
Germany	ImClone Investigational Site	Essen
Germany	ImClone Investigational Site	Essen
Germany	ImClone Investigational Site	Frankfurt
Germany	ImClone Investigational Site	Gauting
Germany	ImClone Investigational Site	Großhansdorf
Germany	ImClone Investigational Site	Halle
Germany	ImClone Investigational Site	Hamburg
Germany	ImClone Investigational Site	Hamburg
Germany	ImClone Investigational Site	Heidelberg
Germany	ImClone Investigational Site	Hemer
Germany	ImClone Investigational Site	Hofheim
Germany	ImClone Investigational Site	Karlsruhe
Germany	ImClone Investigational Site	Lostau
Germany	ImClone Investigational Site	Löwenstein
Germany	ImClone Investigational Site	München
Germany	ImClone Investigational Site	Münster
Germany	ImClone Investigational Site	Regensburg
Germany	ImClone Investigational Site	Regensburg
Germany	ImClone Investigational Site	Ulm
Greece	ImClone Investigational Site	Athens
Greece	ImClone Investigational Site	Heraklion, Crete
Greece	ImClone Investigational Site	Patras
Greece	ImClone Investigational Site	Thessaloniki
Hungary	ImClone Investigational Site	Budapest
Hungary	ImClone Investigational Site	Budapest
Hungary	ImClone Investigational Site	Deszk
Hungary	ImClone Investigational Site	Farkasgyepü
Hungary	ImClone Investigational Site	Mosonmagyaróvár
Hungary	ImClone Investigational Site	Székesfehérvár
Hungary	ImClone Investigational Site	Szombathely
Hungary	ImClone Investigational Site	Törökbálint
Italy	ImClone Investigational Site	Aviano	Pordenone
Italy	ImClone Investigational Site	Frosinone
Italy	ImClone Investigational Site	Genova
Italy	ImClone Investigational Site	Lido di Camaiore	Lucca
Italy	ImClone Investigational Site	Milano
Italy	ImClone Investigational Site	Milano
Italy	ImClone Investigational Site	Monza
Italy	ImClone Investigational Site	Parma
Italy	ImClone Investigational Site	Perugia
Korea, Republic of	ImClone Investigational Site	Incheon
Korea, Republic of	ImClone Investigational Site	Jeonju-si
Korea, Republic of	ImClone Investigational Site	Seongnam
Korea, Republic of	ImClone Investigational Site	Seoul
Korea, Republic of	ImClone Investigational Site	Seoul
Korea, Republic of	ImClone Investigational Site	Seoul
Korea, Republic of	ImClone Investigational Site	Suwon
Philippines	ImClone Investigational Site	Cebu
Philippines	ImClone Investigational Site	Cebu City
Philippines	ImClone Investigational Site	Davao City
Philippines	ImClone Investigational Site	Makati City
Philippines	ImClone Investigational Site	Manila
Philippines	ImClone Investigational Site	Quezon City
Philippines	ImClone Investigational Site	Quezon City
Poland	ImClone Investigational Site	Olsztyn
Poland	ImClone Investigational Site	Otwock
Poland	ImClone Investigational Site	Poznan
Poland	ImClone Investigational Site	Radom
Poland	ImClone Investigational Site	Rzeszow
Poland	ImClone Investigational Site	Szczecin
Poland	ImClone Investigational Site	Torun
Poland	ImClone Investigational Site	Wroclaw
Portugal	ImClone Investigational Site	Coimbra
Portugal	ImClone Investigational Site	Lisboa
Portugal	ImClone Investigational Site	Lisboa
Portugal	ImClone Investigational Site	Porto
Romania	ImClone Investigational Site	Brasov
Romania	ImClone Investigational Site	Bucharest
Romania	ImClone Investigational Site	Bucharest
Romania	ImClone Investigational Site	Cluj-Napoca
Romania	ImClone Investigational Site	Craiova, Dolj
Romania	ImClone Investigational Site	Iasi
Romania	ImClone Investigational Site	Piatra Neamt
Romania	ImClone Investigational Site	Sibiu
Russian Federation	ImClone Investigational Site	Ivanovo
Russian Federation	ImClone Investigational Site	Kirov
Russian Federation	ImClone Investigational Site	Krasnodar
Russian Federation	ImClone Investigational Site	Moscow
Russian Federation	ImClone Investigational Site	Omsk
Russian Federation	ImClone Investigational Site	Smolensk
Russian Federation	ImClone Investigational Site	St. Petersburg
Russian Federation	ImClone Investigational Site	St. Petersburg
Russian Federation	ImClone Investigational Site	St. Petersburg
Russian Federation	ImClone Investigational Site	St. Petersburg
Russian Federation	ImClone Investigational Site	Ufa
Russian Federation	ImClone Investigational Site	Yaroslavl
Serbia	ImClone Investigational Site	Belgrade
Serbia	ImClone Investigational Site	Kragujevac
Serbia	ImClone Investigational Site	Nis
Serbia	ImClone Investigational Site	Sremska Kamenica
Singapore	ImClone Investigational Site	Singapore
Slovakia	ImClone Investigational Site	Bratislava
Slovakia	ImClone Investigational Site	Nitra
Slovakia	ImClone Investigational Site	Poprad
South Africa	ImClone Investigational Site	Bloemfontein	Free State
South Africa	ImClone Investigational Site	Durban	Kwazulu-Natal
South Africa	ImClone Investigational Site	Pretoria	Gauteng
Spain	ImClone Investigational Site	Avila	Castilla Y Leon
Spain	ImClone Investigational Site	Barcelona	Cataluña
Spain	ImClone Investigational Site	Barcelona	Cataluña
Spain	ImClone Investigational Site	Barcelona
Spain	ImClone Investigational Site	L'Hospitalet de Llobregat
Spain	ImClone Investigational Site	Madrid
Spain	ImClone Investigational Site	Madrid	Communidad De Madrid
Spain	ImClone Investigational Site	Madrid	Communidad De Madrid
Spain	ImClone Investigational Site	Majadahonda	Communidad De Madrid
Spain	ImClone Investigational Site	Sevilla	Andalucía
Spain	ImClone Investigational Site	Terrassa	Cataluña
Taiwan	ImClone Investigational Site	Taichung
Taiwan	ImClone Investigational Site	Taichung
Thailand	ImClone Investigational Site	Chiang Mai
Thailand	ImClone Investigational Site	Songkhla
United Kingdom	ImClone Investigational Site	Aberdeen
United Kingdom	ImClone Investigational Site	Bournemouth
United Kingdom	ImClone Investigational Site	Dundee
United Kingdom	ImClone Investigational Site	Edinburgh
United Kingdom	ImClone Investigational Site	Guildford
United Kingdom	ImClone Investigational Site	Liverpool
United Kingdom	ImClone Investigational Site	London
United Kingdom	ImClone Investigational Site	Manchester
United Kingdom	ImClone Investigational Site	Manchester
United Kingdom	ImClone Investigational Site	Preston
United States	ImClone Investigational Site	Akron	Ohio
United States	ImClone Investigational Site	Baltimore	Maryland
United States	ImClone Investigational Site	Camp Hill	Pennsylvania
United States	ImClone Investigational Site	Chandler	Arizona
United States	ImClone Investigational Site	Fairfax	Virginia
United States	ImClone Investigational Site	Fayetteville	Arkansas
United States	ImClone Investigational Site	Galesburg	Illinois
United States	ImClone Investigational Site	Goshen	Indiana
United States	ImClone Investigational Site	Hazard	Kentucky
United States	ImClone Investigational Site	Jefferson City	Missouri
United States	ImClone Investigational Site	Lincoln	Nebraska
United States	ImClone Investigational Site	Memphis	Tennessee
United States	ImClone Investigational Site	New York	New York
United States	ImClone Investigational Site	Sacramento	California
United States	ImClone Investigational Site	Wichita	Kansas

Sponsors (11)

Lead Sponsor	Collaborator
Eli Lilly and Company	ICON Clinical Research, Intertek, Laboratory Corporation of America, Medidata Solutions, Pacific Biomarkers, Parexel, PPD, Sysmex Inostics GmbH, Thermo Fisher Scientific FS, University of Colorado, Denver

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Croatia,  France,  Germany,  Greece,  Hungary,  Italy,  Korea, Republic of,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Singapore,  Slovakia,  South Africa,  Spain,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival Time (OS)	Overall survival is defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive. OS was estimated by the Kaplan-Meier method.	Randomization to Death from Any Cause (Up to 31 Months)
Secondary	Progression-Free Survival (PFS)	PFS is defined as the time from randomization until the first radiographic documentation of objective measured progressive disease as defined by RECIST (Version 1.0), or death from any cause. Progressive Disease (PD) was defined as having at least a 20% increase in the sum of the longest diameter of target lesions. Participants who die without a reported prior progression were considered to have progressed on the day of their death. Participants who did not progress or were lost to follow-up were censored at the day of their last radiographic tumor assessment. If no baseline or postbaseline radiologic assessment was available, the participants were censored at the date of randomization. If death or PD occurs after two or more consecutive missing radiographic visits, censoring occurred at the date of the last radiographic visit prior to the missed visits.	Randomization to Measured Progressive Disease or Death from Any Cause (Up to 31 Months)
Secondary	Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) (Objective Response Rate [ORR])	ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.0, CR was defined as the disappearance of all target and non-target lesions. PR defined as a >=30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD; Percentage of participants was calculated as: (total number of participants with CR or PR from start of the treatment until disease progression or recurrence)/total number of participants treated) * 100.	Baseline to Measured Progressive Disease (Up to 31 Months)
Secondary	Time to Treatment Failure (TTF)	TTF is defined as the time from the date of randomization until the date of the first radiographic documentation of PD, death from any cause, discontinuation of treatment for any reason, or initiation of new cancer therapy. Participants who withdrew from the study for reasons other than progression or death were censored at the date of study withdrawal. Participants who did not meet any of the criteria for treatment failure were censored at their date of last contact in the study.	Randomization to Measured Progressive Disease, Death From Any Cause, Discontinuation of Treatment or Initiation of New Anticancer Therapy (Up to 31 Months)
Secondary	Mean Change From Baseline in Patient Reported Outcomes (PRO) Using the European Quality of Life-5 Dimension (EQ-5D)	The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a three level scale 1-3 (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension).	Baseline, Cycle 6 (Cycle = 3 Weeks)
Secondary	Mean Change From Baseline in PRO Using the Outcomes Lung Cancer Symptom Scale (LCSS)	The LCSS consisted of 9 items: 6 items focused on lung cancer symptoms [loss of appetite, fatigue, cough, dyspnea (shortness of breath), hemoptysis (blood in sputum), and pain] and 3 items were global items (symptom distress, interference with activity level, and global quality of life). Participant responses to each item were measured using visual analogue scales (VAS) with 100-mm lines. A higher score for any item represented a higher level of symptoms/problems. Scores for each of the reported categories ranged from 0 (for best outcome) to 100 (for worst outcome). The Average Symptom Burden Index (ASBI) was the mean of the 6 symptom items of the LCSS, and the Total LCSS was the mean of all 9 LCSS items. ASBI and Total LCSS were not computed for a participant if he/she had 1 or more missing values for the 6 and 9 items, respectively.	Baseline, Cycle 6 (Cycle = 3 Weeks)
Secondary	Number of Participants With an Epidermal Growth Factor Hormone (EGFR) Protein Expression Measured by Immunohistochemistry (IHC)	EGFR IHC Histoscore H-score = weighted sum of % 1+ cells, twice % 2+ cells, and three times % 3+ cells. IHC H-score criteria was used to assess participants with a low EGFR expression defined by a H-score cutoff value of <200 and participants with a high EGFR expression defined by a H-score of cutoff value of >=200.	31 Months
Secondary	Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab		Day 1 of Cycle 2, 3, 4, 5 and 6 Prior to Necitumumab Drug Infusion, Up to 24 Months
Secondary	Number of Participants With a Serum Anti-Necitumumab Antibody Assessment	A participant was considered to have an anti-Necitumumab antibody response if anti-drug antibodies (ADA) were detected at any time point.	Baseline through 31 Months