First-line Treatment of Patients With Stage IV Nonsquamous Non-Small Cell Lung Cancer With Necitumumab (IMC-11F8) and Pemetrexed-Cisplatin

Non Small Cell Lung Cancer Clinical Trial

— INSPIRE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00982111
• Other study ID #: 13908
• Secondary ID: 2009-012574-12CP
• Status: Completed
• Phase: Phase 3
• Start date: November 2, 2009
• Est. completion date: December 23, 2020

Study information

• Verified date: December 2021
• 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 633
• Est. completion date: December 23, 2020
• Est. primary completion date: November 14, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Pemetrexed
500 milligram per square meter (mg/m2) administered Intravenously (I.V.) on Day 1 of every 3-week cycle, for a maximum of six cycles
• Cisplatin
75 mg/m2 administered I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles

Biological:
• Necitumumab
800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle, administered as an I.V.

Locations

Country	Name	City	State
Australia	ImClone Investigational Site	East Bentleigh	Victoria
Australia	ImClone Investigational Site	Hobart	Tasmania
Australia	ImClone Investigational Site	Kogarah	New South Wales
Austria	ImClone Investigational Site	Rankweil
Austria	ImClone Investigational Site	Wien
Austria	ImClone Investigational Site	Wien
Belgium	ImClone Investigational Site	Duffel
Belgium	ImClone Investigational Site	Liège
Belgium	ImClone Investigational Site	Namur
Brazil	ImClone Investigational Site	Barretos - SP
Brazil	ImClone Investigational Site	Brasilia, Distrito Federal
Brazil	ImClone Investigational Site	Goiania - GO
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	Ribeirão Preto - SP
Brazil	ImClone Investigational Site	Salvador
Brazil	ImClone Investigational Site	Santo Andre - SP
Brazil	ImClone Investigational Site	São Paulo - SP
Canada	ImClone Investigational Site	Montreal	Quebec
Croatia	ImClone Investigational Site	Pula
France	ImClone Investigational Site	Caen
France	ImClone Investigational Site	Paris
Germany	ImClone Investigational Site	Berlin
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	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	Mainz
Germany	ImClone Investigational Site	München
Germany	ImClone Investigational Site	Münster
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
Hungary	ImClone Investigational Site	Budapest
Hungary	ImClone Investigational Site	Budapest
Hungary	ImClone Investigational Site	Deszk
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	Parma
Italy	ImClone Investigational Site	Perugia
Poland	ImClone Investigational Site	Olsztyn
Poland	ImClone Investigational Site	Otwock
Poland	ImClone Investigational Site	Poznan
Poland	ImClone Investigational Site	Radom
Poland	ImClone Investigational Site	Szczecin
Poland	ImClone Investigational Site	Wroclaw
Portugal	ImClone Investigational Site	Coimbra
Portugal	ImClone Investigational Site	Lisboa
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	Sibiu
Russian Federation	ImClone Investigational Site	Ivanovo
Russian Federation	ImClone Investigational Site	Kirov
Russian Federation	ImClone Investigational Site	Omsk
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	Yaroslavi
Slovakia	ImClone Investigational Site	Bratislava
Slovakia	ImClone Investigational Site	Nitra
South Africa	ImClone Investigational Site	Bloemfontein	Free State
South Africa	ImClone Investigational Site	Pretoria	Gauteng
Spain	ImClone Investigational Site	Barcelona	Cataluña
Spain	ImClone Investigational Site	Barcelona	Cataluña
Spain	ImClone Investigational Site	L'Hospitalet de Llobregat
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	Andalucia
Spain	ImClone Investigational Site	Terrassa	Cataluña
United Kingdom	ImClone Investigational Site	Aberdeen
United Kingdom	ImClone Investigational Site	Bournemouth
United Kingdom	ImClone Investigational Site	Edinburgh
United Kingdom	ImClone Investigational Site	Guildford
United Kingdom	ImClone Investigational Site	Leeds
United Kingdom	ImClone Investigational Site	Preston
United States	ImClone Investigational Site	Nyack	New York

Sponsors (11)

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

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Croatia,  France,  Germany,  Greece,  Hungary,  Italy,  Poland,  Portugal,  Romania,  Russian Federation,  Slovakia,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival Time (OS)	OS 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 using the Kaplan-Meier method.	Randomization to Death from Any Cause (Up to 31.6 Months)
Secondary	Progression-Free Survival (PFS)	PFS is defined as the time from randomization until the first radiographic documentation of measured progressive disease as defined by RECIST (Version 1.0), or death from any cause. Participants who die without a reported prior progression will be 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 participant was 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 30.4 Months)
Secondary	Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Tumor 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 30.4 Months)
Secondary	Time to Treatment Failure (TTF)	TTF was defined as the time from study enrollment/randomization to the first observation of measured progressive disease, death from any cause, or early discontinuation of treatment or initiation of new anti-cancer therapies. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive Disease (PD) was defined as having at least a 20% increase in sum of longest diameter of target lesions. Time to treatment failure was censored at the date of the last follow-up visit for participants who did not discontinue early, who were still alive, and who have not progressed.	Randomization to Measured Progressive Disease, Death from Any Cause, Discontinuation of Treatment or Initiation of New Anticancer Therapy (Up to 30.4 Months)
Secondary	Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab		Predose Day 1 of Cycle 2,3,4,5 and 6 Prior to Necitumumab Infusion, Up to 23 Weeks
Secondary	Number of Participants With Serum Anti-Necitumumab Antibody Assessment (Immunogenicity)	A participant was considered to have an anti-Necitumumab antibody response if anti-drug antibodies (ADA) were confirmed positive. Treatment emergent antibodies were defined as any anti-Necitumumab antibody titer equal to or greater than 4-fold the participant's baseline titer.	Baseline to Study Completion (Up to 31.6 Months)
Secondary	Mean Change From Baseline in Patient Reported Outcomes (PRO) Using the European Quality of Life-5 Dimensions (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 as Measured Using the 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	Epidermal Growth Factor Hormone (EGFR) Protein Expression Measured by Immunohistochemistry (IHC)	EGFR IHC H-score = weighted sum of % 1+ cells, twice % 2+ cells, and three times % 3+ cells. IHC H-score criteria assesses 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.	Baseline
Secondary	Percentage of Participants With EGFR Measured by IHC	EGFR IHC H-score = weighted sum of % 1+ cells, twice % 2+ cells, and three times % 3+ cells. IHC H-score criteria assesses 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.	Baseline