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

This study is ongoing, but not recruiting participants.
Medidata Solutions
Laboratory Corporation of America
University of Colorado, Denver
Thermo Fisher Scientific
Pacific Biomarkers, Inc.
Inostics GmbH
Information provided by (Responsible Party):
Eli Lilly and Company Identifier:
First received: September 18, 2009
Last updated: November 11, 2014
Last verified: November 2014

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 patient disease than the standard chemotherapy combination alone.

Condition Intervention Phase
Non Small Cell Lung Cancer
Drug: pemetrexed
Drug: cisplatin
Biological: IMC-11F8
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Overall survival time (OS) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
    Overall survival time is measured as randomization to date of death from any cause. Participants who are alive when the study achieves 474 deaths or is lost to follow-up will have their overall survival time censored on the last date the participant is known to be alive.

Secondary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
    PFS is measured from randomization to the first radiographically documented progressive disease (PD) or death. Participants alive and without disease progression or lost to follow-up will be censored to the day of their last radiographic assessment.

  • Objective response rate (ORR) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
    Proportion of participants who achieved a best overall response of complete response (CR) or partial response (PR) compared to the total number of participants. Best response is categorized using the Response Evaluation Criteria In Solid Tumors (RECIST) (ver 1.0) guidelines.

  • Time to Treatment Failure (TTF) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
    TTF is defined as the time from the date of randomization until the date of the first radiographic documentation of PD, death due to any cause, discontinuation of treatment for any reason, or initiation of new cancer therapy.

  • Minimum concentration (Cmin) of IMC-11F8 [ Time Frame: Day 1 of Cycle 1,2,3,4,5 and 6 prior to 11F8 infusion ] [ Designated as safety issue: No ]
  • Serum Anti-IMC-11F8 Antibody Assessment (immunogenicity) [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
    Screen for the development of circulating antibodies against IMC-11F8

  • Change from baseline in Patient Reported Outcomes (PRO) using the European Quality of Life-5 Dimension (EQ-5D) at 30 months. [ Time Frame: 30 months ] [ Designated as safety issue: No ]
  • Change from baseline in Patient-Reported Outcomes (PRO) as measured using the Lung Cancer Symptom Scale (LCSS) at 30 months [ Time Frame: 30 months ] [ Designated as safety issue: No ]
  • EGFR protein expression measured by immunohistochemistry [ Time Frame: 30 months ] [ Designated as safety issue: No ]

Enrollment: 633
Study Start Date: November 2009
Estimated Study Completion Date: December 2015
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMC-11F8 + pemetrexed + cisplatin
IMC-11F8 + pemetrexed + cisplatin
Drug: pemetrexed
500 mg/m2 (I.V.) on Day 1 of every 3-week cycle, for a maximum of six cycles
Other Name: Alimta®
Drug: cisplatin
75 mg/m2 (I.V.) on Day 1 of every 3-week cycle, for a maximum of six cycles
Biological: IMC-11F8
800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle, administered as an I.V. infusion
Other Name: necitumumab
Active Comparator: pemetrexed + cisplatin
pemetrexed + cisplatin
Drug: pemetrexed
500 mg/m2 (I.V.) on Day 1 of every 3-week cycle, for a maximum of six cycles
Other Name: Alimta®
Drug: cisplatin
75 mg/m2 (I.V.) on Day 1 of every 3-week cycle, for a maximum of six cycles

Detailed Description:

Multinational, randomized, multicenter, open-label Phase 3 study of 633 patients with advanced, nonsquamous (Stage IV) NSCLC. Patients 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).

Patients 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); patients 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 patients 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 patient is alive, or until the end of the trial.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 (patients 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 patients surgically sterile or compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period
  • Female patients 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 EGFR, vascular endothelial growth factor (VEGF), or VEGF receptor
  • Received previous chemotherapy for advanced NSCLC (patients 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. Patients 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 patient's ability to complete the study or sign an informed consent document The patient 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 patient with previous history of malignancy other than NSCLC is eligible, provided that he/she has been free of disease for ≥ 3 years
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00982111

  Show 106 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Medidata Solutions
Laboratory Corporation of America
University of Colorado, Denver
Thermo Fisher Scientific
Pacific Biomarkers, Inc.
Inostics GmbH
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company Identifier: NCT00982111     History of Changes
Other Study ID Numbers: 13908, 2009-012574-12, CP11-0805, I4X-IE-JFCB
Study First Received: September 18, 2009
Last Updated: November 11, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Canada: Health Canada
Croatia: Ministry of Health and Social Care
France: ANSM - French Health Products Safety Agency
Germany: Paul-Ehrlich-Institut
Greece: Ministry of Health and Welfare
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Italy: The Italian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Non Small Cell Lung Cancer
First line treatment
Epidermal Growth Factor Receptor (EGFR)

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses processed this record on November 24, 2014