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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Parexel
PPD
Medidata Solutions
Laboratory Corporation of America
University of Colorado, Denver
Thermo Fisher Scientific
ICON Clinical Research
Pacific Biomarker Inc.
Inostics GmbH
Intertek
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00981058
First received: September 18, 2009
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

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 (IMC-11F8), given together with a standard chemotherapy combination consisting of cisplatin and gemcitabine will be more effective in improving patient disease than the standard chemotherapy combination alone.


Condition Intervention Phase
Non Small Cell Lung Cancer
Biological: necitumumab
Drug: gemcitabine
Drug: cisplatin
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 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)

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 31 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 844 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 31 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 31 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 31 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.

  • Change from baseline in Patient Reported Outcomes (PRO) using the European Quality of Life-5 Dimension (EQ-5D) at 31-months [ Time Frame: 31 months ] [ Designated as safety issue: No ]
    Change from baseline to the end of therapy visit approximately 31-months.

  • Change from baseline in Patient Reported Outcomes (PRO) using the Outcomes Lung Cancer Symptom Scale (LCSS) at 31-months. [ Time Frame: 31 months ] [ Designated as safety issue: No ]
    Change from baseline to the end of therapy visit approximately 31-months.

  • Minimum concentration (Cmin) of IMC-11F8 [ Time Frame: Day 1 of Cycle 1, 2, 3, 4, 5 and 6 prior to 11F8 drug infusion ] [ Designated as safety issue: No ]
  • Serum Anti-IMC-11F8 (necitumumab) Antibody Assessment [ Time Frame: 31 months ] [ Designated as safety issue: Yes ]
    Number of participants who showed detectable levels of antibody at any point in the study


Enrollment: 1093
Study Start Date: January 2010
Estimated Study Completion Date: December 2014
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: necitumumab + gemcitabine + cisplatin
necitumumab + gemcitabine + cisplatin
Biological: necitumumab

800 mg I.V. infusion on Days 1 and 8 of every 3 week cycle.

Continues until progressive disease, toxicity, noncompliance, or withdrawal.

Other Names:
  • IMC-11F8
  • anti-EGFR
  • LY3012211
Drug: gemcitabine

1250 mg/m2 on Days 1 and 8 of every 3 week cycle.

Continues for a maximum of six cycles.

Other Name: Gemzar®
Drug: cisplatin

75 mg/m2 IV on Day 1 of every 3 week cycle.

Continues for a maximum of six cycles.

Active Comparator: gemcitabine + cisplatin
gemcitabine + cisplatin
Drug: gemcitabine

1250 mg/m2 on Days 1 and 8 of every 3 week cycle.

Continues for a maximum of six cycles.

Other Name: Gemzar®
Drug: cisplatin

75 mg/m2 IV on Day 1 of every 3 week cycle.

Continues for a maximum of six cycles.


Detailed Description:

Multinational, randomized, multicenter, open-label, Phase III study of 1093 patients (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 (IMC-11F8) 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). Patients 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); patients in Arm A only will continue to receive necitumumab (IMC-11F8) 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.

  Eligibility

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

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) (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 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 patient is 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 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 (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)
  • 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. 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
  • 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 patient'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 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 ClinicalTrials.gov identifier: NCT00981058

  Show 191 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Parexel
PPD
Medidata Solutions
Laboratory Corporation of America
University of Colorado, Denver
Thermo Fisher Scientific
ICON Clinical Research
Pacific Biomarker Inc.
Inostics GmbH
Intertek
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00981058     History of Changes
Other Study ID Numbers: 13909, CP11-0806, I4X-IE-JFCC, 2009-013838-25
Study First Received: September 18, 2009
Last Updated: May 20, 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
Italy: The Italian Medicines Agency
Korea: Food and Drug Administration
Philippines: Bureau of Food and Drugs
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
Singapore: Health Sciences Authority
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Taiwan: Department of Health
Thailand: Ministry of Public Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gemcitabine
Cisplatin
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014