Clinical trial NCT00994097: NGR-hTNF in Combination With Standard Chemotherapy to Treat Patients With Advanced Non-small Cell Lung Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: NGR-hTNF
Randomized controlled trial
Gemcitabine
Cisplatin
Pemetrexed
Carcinoma, non-small cell lung
Lead sponsor: AGC Biologics S.p.A.
Sponsor class: INDUSTRY
First posted: 2009-10-14
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Every 6 weeks during study treatment and every 6 weeks during the follow-up before PD
Secondary outcomes:
measure: Safety according to NCI-CTCAE criteria (version 3)
timeFrame: from the date of randomization until 28 days after last treatment
measure: Objective response rate
timeFrame: Every 6 weeks during study treatment and every 6 weeks during the follow-up before PD
measure: Duration of response (DR)
timeFrame: from the time of first recorded evidence of complete response or partial response until the progressive disease objectively documented
measure: Overall survival (OS)
timeFrame: from the randomization until to the date of patient death or discontinuation from the study
Other outcomes:
Locations:
city: Genoa
country: Italy
facility: Istituto Nazionale per la ricerca sul cancro
city: Milan
country: Italy
facility: Fondazione San Raffaele del Monte Tabor
city: Milan
country: Italy
facility: Istituto Nazionale dei Tumori
city: Milan
country: Italy
facility: Istituto Europeo Oncologico
Study officials:
affiliation: AGC Biologics S.p.A.
name: Antonio Lambiase, MD
role: STUDY_DIRECTOR
References: