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

Study Description

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Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: NGR-hTNF; Drug: Cisplatin; Drug: Gemcitabine; Drug: Pemetrexed	Phase 2

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	102 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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)
Study Start Date :	July 2009
Estimated Primary Completion Date :	June 2016
Estimated Study Completion Date :	June 2016

Arms and Interventions

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

Outcome Measures

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Primary Outcome Measures :

1. Progression-free survival (PFS) defined as time from the randomization until to objective disease progression or death due any cause. [ Time Frame: from the randomization until to objective disease progression or death ]

Secondary Outcome Measures :

1. Safety profile of NGR-hTNF in combination with standard chemotherapy as compared to standard chemotherapy alone. [ Time Frame: after initiation of trial treatment until to 28 days after the last treatment administration ]
2. Response rate defined as the percentage of subjects achieving at a specific % tumor volume reduction in according to RECIST criteria. [ Time Frame: Every 6 weeks during study treatment and every 6 weeks during the follow-up before PD ]
3. 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. [ Time Frame: from the time of first recorded evidence of complete response or partial response until the progressive disease objectively documented ]
4. Overall survival (OS) defined as the time from the randomization until to the date of patient death from any case or discontinuation from the study. [ Time Frame: from the randomization until to the date of patient death or discontinuation from the study ]

Eligibility Criteria

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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:

1. 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.
2. Age ≥18 years
3. Life expectancy more than 3 months
4. ECOG performance status 0-1
5. At least one unidimensional measurable lesion (as per RECIST criteria)

6. 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

7. 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
8. Patients must give written informed consent to participate in the study

Exclusion criteria:

1. Prior chemotherapy or treatment with another systemic anti-cancer agent (for example monoclonal antibody, tyrosine kinase inhibitor).
2. Patients must not receive any other investigational agents while on study
3. 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
4. Uncontrolled hypertension
5. Prolonged QTc interval (congenital or acquired)
6. Patient with significant peripheral vascular disease
7. 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).
8. Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol
9. Known hypersensitivity/allergic reaction or contraindications to human albumin preparations or to any of the excipients
10. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol
11. 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.

Contacts and Locations

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Locations

Italy
Istituto Nazionale per la ricerca sul cancro
Genoa, Italy, 16132
Fondazione San Raffaele del Monte Tabor
Milan, Italy, 20132
Istituto Nazionale dei Tumori
Milan, Italy, 20133
Istituto Europeo Oncologico
Milan, Italy

Sponsors and Collaborators

MolMed S.p.A.

Investigators

Study Director:	Antonio Lambiase, MD	MolMed S.p.A.

More Information

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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	MolMed S.p.A.
ClinicalTrials.gov Identifier:	NCT00994097 History of Changes
Other Study ID Numbers:	NGR014; 2008-002703-20 ( EudraCT Number )
First Posted:	October 14, 2009
Last Update Posted:	October 9, 2015
Last Verified:	October 2015

Keywords provided by MolMed S.p.A.:

NGR-hTNF; Randomized controlled trial; Gemcitabine	Cisplatin; Pemetrexed; Carcinoma, non-small cell lung

Additional relevant MeSH terms:

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; Gemcitabine; Cisplatin; Pemetrexed	Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors