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

Lilly

Status and phase

Active, not recruiting

Phase 3

Conditions

Non Small Cell Lung Cancer

Treatments

Biological: Necitumumab

Drug: Gemcitabine

Drug: Cisplatin

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00981058

CP11-0806 (Other Identifier)

I4X-IE-JFCC (Other Identifier)

2009-013838-25 (EudraCT Number)

13909

Details and patient eligibility

About

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.

Full 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.

Enrollment

1,093 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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