First-line Treatment of Patients With Stage IV Nonsquamous Non-Small Cell Lung Cancer With Necitumumab (IMC-11F8) and Pemetrexed-Cisplatin (INSPIRE)
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| ClinicalTrials.gov Identifier: NCT00982111 |
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Recruitment Status :
Completed
First Posted : September 22, 2009
Results First Posted : June 27, 2016
Last Update Posted : January 11, 2022
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Sponsor:
Eli Lilly and Company
Collaborators:
Quintiles, Inc.
Parexel
PPD
Medidata Solutions
Laboratory Corporation of America
University of Colorado, Denver
Thermo Fisher Scientific, Inc
Pacific Biomarkers
Intertek
Sysmex Inostics GmbH
Information provided by (Responsible Party):
Eli Lilly and Company
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Non Small Cell Lung Cancer | Drug: Pemetrexed Drug: Cisplatin Biological: Necitumumab | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 633 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | November 2, 2009 |
| Actual Primary Completion Date : | November 14, 2012 |
| Actual Study Completion Date : | December 23, 2020 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
MedlinePlus related topics:
Lung Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Necitumumab + Pemetrexed + Cisplatin
Necitumumab + Pemetrexed + Cisplatin
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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
Other Names:
Drug: 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.
Other Names:
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Active Comparator: Pemetrexed + Cisplatin
Pemetrexed + Cisplatin
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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
Other Names:
Drug: Cisplatin 75 mg/m2 administered I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles |
Primary Outcome Measures :
- Overall Survival Time (OS) [ Time Frame: Randomization to Death from Any Cause (Up to 31.6 Months) ]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.
Secondary Outcome Measures :
- Progression-Free Survival (PFS) [ Time Frame: Randomization to Measured Progressive Disease or Death from Any Cause (Up to 30.4 Months) ]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.
- Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Tumor Response Rate [ORR]) [ Time Frame: Baseline to Measured Progressive Disease (Up to 30.4 Months) ]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.
- Time to Treatment Failure (TTF) [ Time Frame: Randomization to Measured Progressive Disease, Death from Any Cause, Discontinuation of Treatment or Initiation of New Anticancer Therapy (Up to 30.4 Months) ]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.
- Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab [ Time Frame: Predose Day 1 of Cycle 2,3,4,5 and 6 Prior to Necitumumab Infusion, Up to 23 Weeks ]
- Number of Participants With Serum Anti-Necitumumab Antibody Assessment (Immunogenicity) [ Time Frame: Baseline to Study Completion (Up to 31.6 Months) ]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.
- Mean Change From Baseline in Patient Reported Outcomes (PRO) Using the European Quality of Life-5 Dimensions (EQ-5D) [ Time Frame: Baseline, Cycle 6 (Cycle = 3 weeks) ]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).
- Mean Change From Baseline in PRO as Measured Using the Lung Cancer Symptom Scale (LCSS) [ Time Frame: Baseline, Cycle 6 (Cycle =3 Weeks) ]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.
- Epidermal Growth Factor Hormone (EGFR) Protein Expression Measured by Immunohistochemistry (IHC) [ Time Frame: Baseline ]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.
- Percentage of Participants With EGFR Measured by IHC [ Time Frame: Baseline ]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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00982111
Locations
Show 101 study locations
Sponsors and Collaborators
Eli Lilly and Company
Quintiles, Inc.
Parexel
PPD
Medidata Solutions
Laboratory Corporation of America
University of Colorado, Denver
Thermo Fisher Scientific, Inc
Pacific Biomarkers
Intertek
Sysmex Inostics GmbH
Investigators
| Study Director: | 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) | Eli Lilly and Company |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Eli Lilly and Company |
| ClinicalTrials.gov Identifier: | NCT00982111 |
| Other Study ID Numbers: |
13908 2009-012574-12 ( EudraCT Number ) CP11-0805 ( Other Identifier: ImClone Systems ) I4X-IE-JFCB ( Other Identifier: Eli Lilly and Company ) |
| First Posted: | September 22, 2009 Key Record Dates |
| Results First Posted: | June 27, 2016 |
| Last Update Posted: | January 11, 2022 |
| Last Verified: | December 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and assigned data sharing agreement. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting. |
| Access Criteria: | A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement. |
| URL: | https://vivli.org/ |
Keywords provided by Eli Lilly and Company:
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Nonsquamous Non Small Cell Lung Cancer First line treatment |
Monoclonal Antibodies Epidermal Growth Factor Receptor (EGFR) |
Additional relevant MeSH terms:
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Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic |
Bronchial Neoplasms Pemetrexed Necitumumab Antineoplastic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors Antineoplastic Agents, Immunological |