Non-small Cell Lung Cancer
Conditions
Keywords
NGR-hTNF, Randomized controlled trial, Gemcitabine, Cisplatin, Pemetrexed, Carcinoma, non-small cell lung
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.
Interventions
DRUGNGR-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
DRUGCisplatin
Cisplatin: 80 mg/m² intravenous infusion on day 1 every 3 weeks for a maximum of 6 cycles
DRUGGemcitabine
Gemcitabine: 1,250 mg/m² intravenous infusion on days 1 and 8 every 3 weeks for a maximum of 6 cycles
DRUGPemetrexed
Pemetrexed: 500 mg/m² intravenous infusion on day 1 every 3 weeks for a maximum of 6 cycles
Sponsors
AGC Biologics S.p.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Every 6 weeks during study treatment and every 6 weeks during the follow-up before PD | PFS evaluated according to Response evaluation criteria in solid tumors (RECIST) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety according to NCI-CTCAE criteria (version 3) | from the date of randomization until 28 days after last treatment | To evaluate safety profile related to NGR-hTNF in combination with standard chemotherapy |
| Objective response rate | Every 6 weeks during study treatment and every 6 weeks during the follow-up before PD | Antitumor activity defined as response rate evaluated according to Response evaluation criteria in solid tumors (RECIST) |
| Duration of response (DR) | from the time of first recorded evidence of complete response or partial response until the progressive disease objectively documented | 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. |
| Overall survival (OS) | from the randomization until to the date of patient death or discontinuation from the study | 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 |
Countries
Italy
Outcome results
None listed