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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
MolMed S.p.A.
ClinicalTrials.gov Identifier:
NCT00994097
First received: October 13, 2009
Last updated: January 28, 2013
Last verified: January 2013
  Purpose

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 Intervention Phase
Non-small Cell Lung Cancer
Drug: NGR-hTNF
Drug: Cisplatin
Drug: Gemcitabine
Drug: Pemetrexed
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by MolMed S.p.A.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 102
Study Start Date: July 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
NGR-hTNF in combination or with cisplatin/gemcitabine regimen in patients with squamous histology (including also generic diagnosis of NSCLC without further subtype classification) or with cisplatin/pemetrexed regimen in patients with nonsquamous histology (including adenocarcinoma and large-cell carcinoma).
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
The control arm is represented by standard chemotherapy regimen alone: cisplatin/gemcitabine regimen is administered in patients with squamous histology (including also generic diagnosis of NSCLC without further subtype classification) and cisplatin/pemetrexed regimen is administered in patients with nonsquamous histology (including adenocarcinoma and large-cell carcinoma).
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00994097

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

No publications provided

Responsible Party: MolMed S.p.A.
ClinicalTrials.gov Identifier: NCT00994097     History of Changes
Other Study ID Numbers: NGR014, 2008-002703-20
Study First Received: October 13, 2009
Last Updated: January 28, 2013
Health Authority: Italy: Ethics Committee

Keywords provided by MolMed S.p.A.:
NGR-hTNF
Randomized controlled trial
Gemcitabine
Cisplatin
Pemetrexed
Carcinoma, non-small cell lung

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gemcitabine
Pemetrexed
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on July 28, 2014