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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00994097
Recruitment Status : Completed
First Posted : October 14, 2009
Last Update Posted : September 27, 2018
Sponsor:
Information provided by (Responsible Party):
AGC Biologics S.p.A.

Tracking Information
First Submitted Date  ICMJE October 13, 2009
First Posted Date  ICMJE October 14, 2009
Last Update Posted Date September 27, 2018
Actual Study Start Date  ICMJE July 2009
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 25, 2018)
Progression-free survival (PFS) [ Time Frame: 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)
Original Primary Outcome Measures  ICMJE
 (submitted: October 13, 2009)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 25, 2018)
  • Safety according to NCI-CTCAE criteria (version 3) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2009)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE NGR-hTNF in Combination With Standard Chemotherapy to Treat Patients With Advanced Non-small Cell Lung Cancer
Official Title  ICMJE 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)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: NGR-hTNF
    • Drug: Cisplatin
    • Drug: Gemcitabine
    • Drug: Pemetrexed
  • 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
    Interventions:
    • Drug: Cisplatin
    • Drug: Gemcitabine
    • Drug: Pemetrexed
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 25, 2018)
121
Original Estimated Enrollment  ICMJE
 (submitted: October 13, 2009)
102
Actual Study Completion Date  ICMJE March 2017
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00994097
Other Study ID Numbers  ICMJE NGR014
2008-002703-20 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AGC Biologics S.p.A.
Study Sponsor  ICMJE AGC Biologics S.p.A.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Antonio Lambiase, MD AGC Biologics S.p.A.
PRS Account AGC Biologics S.p.A.
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP