NGR-hTNF in Combination With Standard Chemotherapy to Treat Patients With Advanced Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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The main objective of this study is to demonstrate superiority in progression-free survival (PFS) when NGR-hTNF is added to standard chemotherapy regimen (cisplatin/gemcitabine or cisplatin/pemetrexed) in locally advanced (stage IIIb with supraclavicular lymph node metastases or malignant pleural or pericardial effusion), metastatic (stage IV) or recurrent non-small cell lung cancer (NSCLC).

Detailed Description
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Eligible patients will be randomly assigned to a standard chemotherapy regimen plus low-dose (0.8 mcg/m^2) NGR-hTNF or standard chemotherapy alone, through a centralized randomization process using the following stratification factors: performance status (0 vs 1) and histology (squamous vs non-squamous). In both arms the choice between the two chemotherapy regimens will be based on the histologic subtype: in patients with squamous histology (including also generic diagnosis of NSCLC without further subtype classification) is recommended cisplatin/gemcitabine regimen, in patients with nonsquamous histology (including adenocarcinoma and large-cell carcinoma) is recommended cisplatin/pemetrexed regimen.

Official Title
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NGR014: Randomized Phase II Study of NGR-hTNF in Combination With Standard Chemotherapy Versus Standard Chemotherapy Alone in Previously Untreated Patients With Advanced Non-small Cell Lung Cancer (NSCLC)

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: NGR-hTNF
* Drug: Cisplatin
* Drug: Gemcitabine
* Drug: Pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histologically or cytologically documented inoperable, locally advanced (stage IIIb with supraclavicular lymph node metastases or malignant pleural or pericardial effusion), metastatic (stage IV) or recurrent NSCLC. Mixed tumors should be categorized according to the predominant cell type. Age ≥18 years Life expectancy more than 3 months ECOG performance status 0-1 At least one unidimensional measurable lesion (as per RECIST criteria) Adequate baseline bone marrow, hepatic and renal function, defined as follows: Neutrophils >1.5 x 10^9/L and platelets > 100 x 10^9/L Bilirubin <1.5 x ULN AST and/or ALT <2.5 x ULN in absence of liver metastasis AST and/or ALT <5 x ULN in presence of liver metastasis Serum creatinine <1.5 x ULN Creatinine clearance (estimated according to Cockcroft-Gault formula) ≥ 50 ml/min Patients may have had prior therapy providing the following conditions are met: Radiation therapy: wash-out period of 28 days Surgery: wash-out period of 14 days Patients must give written informed consent to participate in the study Exclusion criteria: Prior chemotherapy or treatment with another systemic anti-cancer agent (for example monoclonal antibody, tyrosine kinase inhibitor). Patients must not receive any other investigational agents while on study Patients with myocardial infarction within the last six (6) months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication Uncontrolled hypertension Prolonged QTc interval (congenital or acquired) Patient with significant peripheral vascular disease History or evidence upon physical examination of CNS disease unless adequately treated (e.g., primary brain tumor, any brain metastasis, seizure not controlled with standard medical therapy, or history of stroke). Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol Known hypersensitivity/allergic reaction or contraindications to human albumin preparations or to any of the excipients Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol Pregnancy or lactation. Patients - both males and females - with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of child-bearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: NGR-hTNF + cisplatin/gemcitabine or cisplatin/pemetrexed<br>NGR-hTNF with cisplatin/gemcitabine regimen in patients with squamous histology or with cisplatin/pemetrexed regimen in patients with nonsquamous histology | Drug: NGR-hTNF<br>* NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every 3 weeks until confirmed evidence of disease progression or unacceptable toxicity occurs<br>Drug: Cisplatin<br>* Cisplatin: 80 mg/m² intravenous infusion on day 1 every 3 weeks for a maximum of 6 cycles<br>Drug: Gemcitabine<br>* Gemcitabine: 1,250 mg/m² intravenous infusion on days 1 and 8 every 3 weeks for a maximum of 6 cycles<br>Drug: Pemetrexed<br>* Pemetrexed: 500 mg/m² intravenous infusion on day 1 every 3 weeks for a maximum of 6 cycles<br>|
| Active Comparator: B: cisplatin/gemcitabine or cisplatin/pemetrexed<br>Cisplatin/gemcitabine regimen is administered in patients with squamous histology and cisplatin/pemetrexed regimen is administered in patients with nonsquamous histology | Drug: Cisplatin<br>* Cisplatin: 80 mg/m² intravenous infusion on day 1 every 3 weeks for a maximum of 6 cycles<br>Drug: Gemcitabine<br>* Gemcitabine: 1,250 mg/m² intravenous infusion on days 1 and 8 every 3 weeks for a maximum of 6 cycles<br>Drug: Pemetrexed<br>* Pemetrexed: 500 mg/m² intravenous infusion on day 1 every 3 weeks for a maximum of 6 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | PFS evaluated according to Response evaluation criteria in solid tumors (RECIST) | Every 6 weeks during study treatment and every 6 weeks during the follow-up before PD | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety according to NCI-CTCAE criteria (version 3) | To evaluate safety profile related to NGR-hTNF in combination with standard chemotherapy | from the date of randomization until 28 days after last treatment | 
| Objective response rate | Antitumor activity defined as response rate evaluated according to Response evaluation criteria in solid tumors (RECIST) | Every 6 weeks during study treatment and every 6 weeks during the follow-up before PD | 
| Duration of response (DR) | defined as the time that measurement criteria are met for complete response or partial response (whichever status is recorded first) until the progressive disease is objectively documented. | from the time of first recorded evidence of complete response or partial response until the progressive disease objectively documented | 
| Overall survival (OS) | Defined as the time from the date of randomization until the date of death due to any cause or the last date the patient was known to be alive | from the randomization until to the date of patient death or discontinuation from the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NGR-hTNF, Randomized controlled trial, Gemcitabine, Cisplatin, Pemetrexed, Carcinoma, non-small cell lung