A Phase III Randomized, Double-blind, Placebo Controlled Trial Comparing the Efficacy of Gemcitabine, Cisplatin and Sorafenib to Gemcitabine, Cisplatin and Placebo in First-Line Treatment of Patients With Stage IIIb With Effusion and Stage IV Non-Small Cell Lung Cancer (NSCLC)

Browse trials for

• Carcinoma, Non-Small-Cell Lung 6,645
• Neoplasms 9,616

Keywords

• Non-Small Cell Lung Cancer (NSCLC)
• Cancer

Carcinoma, Non-Small-Cell Lung

6,645 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,665 are open to participants now.

This study's enrollment of 904 is above the median of 62 across 5,327 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.

Lead sponsor

Bayer is the lead sponsor of 1,674 studies on the registry; 53 are open to participants now.

Of its 214 completed or terminated interventional studies of FDA-regulated products, 130 (61%) have results posted.

Study arms

• Experimental
  Sorafenib (Nexavar, BAY43-9006) + GC

  Up to 6 cycles (21 days per cycle) of gemcitabine (G) and cisplatin (C) with sorafenib. Day 1: gemcitabine 1250 mg/ m\^2 infusion (IV), followed by cisplatin 75 mg/ m\^2 IV; Day 8: gemcitabine 1250 mg/ m\^2 IV; Days 1-21: sorafenib 2 tablets (200 mg) taken orally (po) twice daily (bid). If the patient had radiological evidence of stable disease (SD) or better after completing up to 6 cycles in the Chemotherapy Phase, the patient could continue to Maintenance Phase, during which sorafenib was administered 400 mg bid until criteria for withdrawal were met.

  Drug: Sorafenib (Nexavar, BAY43-9006) · Drug: Gemcitabine · Drug: Cisplatin

• Placebo comparator
  Placebo + GC

  Up to 6 cycles (21 days per cycle) of gemcitabine (G) and cisplatin (C) with placebo. Day 1: gemcitabine 1250 mg/ m\^2 infusion (IV), followed by cisplatin 75 mg/ m\^2 IV; Day 8: gemcitabine 1250 mg/ m\^2 IV; Days 1-21: placebo 2 tablets po bid. If the patient had radiological evidence of SD or better after completing up to 6 cycles in the Chemotherapy Phase, the patient could continue to Maintenance Phase, during which 2 placebo tablets were administered bid until criteria for withdrawal were met.

  Drug: Placebo · Drug: Gemcitabine · Drug: Cisplatin

Interventions

• DrugSorafenib (Nexavar, BAY43-9006)

  Multikinase inhibitor, Sorafenib 400 mg po bid; applied in combination with chemotherapy components: Gemcitabine 1250 mg/m\^2 IV, Cisplatin 75 mg/m\^2 IV

• DrugPlacebo

  Placebo 2 tablets po bid; applied in combination with chemotherapy components: Gemcitabine 1250 mg/m\^2 IV, Cisplatin 75 mg/m\^2 IV

• DrugGemcitabine

  Chemotherapy component; Gemcitabine 1250 mg/m\^2 IV

• DrugCisplatin

  Chemotherapy component; Cisplatin 75 mg/m\^2 IV

Primary outcomes

1. Overall Survival (OS) in the ITT (Non-squamous) Population

   Overall survival (OS) was defined as the time from date of randomization to death due to any cause. Patients still alive at the time of analysis were censored at their last date of last contact.

   Time frame: from randomization of the first patient until 38 months or date of death of any cause whichever came first

Secondary outcomes

1. OS in the ITT (Both Squamous and Non-squamous) Population

   OS was defined as the time from date of randomization to death due to any cause. Patients still alive at the time of analysis were censored at their last date of last contact.

   Time frame: from randomization of the first patient until 38 months or date of death of any cause whichever came first

2. OS in the ITT (Squamous) Population

   OS was defined as the time from date of randomization to death due to any cause. Patients still alive at the time of analysis were censored at their last date of last contact.

   Time frame: from randomization of the first patient until 38 months or date of death of any cause whichever came first

3. Progression-free Survival (PFS) in the ITT (Non-squamous) Population

   PFS was defined as the time from date of randomization to disease progression (radiological or clinical, whichever was earlier, based on Investigator-assessment using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0) or death due to any cause, whichever occured first. Patients without progression or death at the time of analysis were censored at their last date of tumor evaluation. Disease progression: increase in the sum of tumor lesion sizes or new lesions.

   Time frame: from randomization of the first patient until 38 months or date of death or progression whichever came first, assessed until discontinuation every 6 weeks up to 9 months and then every 12 weeks

4. Time to Progression (TTP) in the ITT (Non-squamous) Population

   TTP was defined as the time from date of randomization to disease progression (radiological or clinical, whichever was earlier, based on Investigator-assessment using RECIST version 1.0). Patients without progression at the time of analysis or death before progression were censored at their last date of tumor evaluation. Disease progression: increase in the sum of tumor lesion sizes or new lesions.

   Time frame: from randomization of the first patient until 38 months or date of death or progression whichever came first, assessed until discontinuation every 6 weeks up to 9 months and then every 12 weeks

5. Percentage of Participants With Different Tumor Response in the ITT (Non-squamous) Population

   Tumor response (= Best Overall Response) of a patient was defined as the best tumor response (confirmed Complete Response (CR: disappearance of tumor lesions), confirmed Partial Response (PR: a decrease of at least 30% in the sum of tumor lesion sizes), Stable Disease (SD: steady state of disease), or Progressive Disease (PD: an increase in the sum of tumor lesions sizes or new lesions)) observed during trial period assessed according to the RECIST criteria (version 1.0) based on Investigator-assessment.

   Time frame: from randomization of the first patient until 38 months or date of death or progression whichever came first, assessed until discontinuation every 6 weeks up to 9 months and then every 12 weeks

6. Disease Control (DC) in the ITT (Non-squamous) Population

   DC was defined as the total number of patients whose best response was not PD according to RECIST (version 1.0) by Investigator-assessment (= total number of CR + total number of PR + total number of SD; CR or PR had to be maintained for at least 28 days from the first demonstration of that rating, SD had to be documented at least once more than 6 weeks from baseline). PD: an increase in the sum of tumor lesions sizes or new lesions.

   Time frame: from randomization of the first patient until 38 months or date of death or progression whichever came first, assessed until discontinuation every 6 weeks up to 9 months and then every 12 weeks

7. Duration of Response in the ITT (Non-squamous) Population

   Duration of response was defined as the time from date of first documented objective response of PR or CR, whichever was noted earlier, to date of disease progression or death (if death occurred before progression was documented). Patients without disease progression at the time of analysis or death before progression were censored at the last date of tumor evaluation. Disease progression: increase in the sum of tumor lesion sizes or new lesions.

   Time frame: from randomization of the first patient until 38 months or date of death or progression whichever came first, assessed until discontinuation every 6 weeks up to 9 months and then every 12 weeks

8. Duration of Stable Disease (SD) in the ITT (Non-squamous) Population

   Duration of SD was defined as the time from date of randomization to date that disease progression (radiological or clinical, whichever was earlier) was first documented. Patients without disease progression at the time of analysis or death before progression were censored at the date of their last tumor assessment.(Disease progression: increase in the sum of tumor lesion sizes or new lesions.) Duration of stable disease was only evaluated in patients failing to achieve a best response of CR or PR.

   Time frame: from randomization of the first patient until 38 months or date of death or progression whichever came first, assessed until discontinuation every 6 weeks up to 9 months and then every 12 weeks

9. Time to Response (TTR) in the ITT (Non-squamous) Population

   TTR for patients who achieved a best response (CR or PR) was defined as the time from date of randomization to the earliest date that response was first documented.

   Time frame: from randomization of the first patient until 38 months or date of death of any cause whichever came first

10. Functional Assessment of Cancer Treatment-Lung (FACT-L) Scores in the ITT (Non-squamous) Population

    The FACT-L measures health related quality of life (HRQOL) and composes of five domains: the four domains (physical well being, emotional well being, social well being, functional well being) from the Functional Assessment of Cancer Treatment-General scale (FACT-G) and the lung cancer subscale (LCS). The FACT-L total score ranges from 0 to 136, higher scores represent better HRQOL.

    Time frame: from randomization of the first patient until 38 months

11. Lung Cancer Subscale (LCS) Scores in the ITT (Non-squamous) Population

    LCS is a subscale of FACT-L measuring lung cancer specific symptoms. The LCS scores range from 0 to 28, higher scores represent fewer lung cancer symptoms.

    Time frame: from randomization of the first patient to 38 months later or death whatever occurs first.

12. Time to Symptomatic Deterioration (TSD) in the ITT (Non-squamous) Population

    TSD is defined as the time from randomization to the date of symptomatic deterioration (≥3 point decline in the LCS score that is maintained for at least 2 consecutive cycles) or death if death occurs before these 2 consecutive cycles are completed.

    Time frame: from randomization of the first patient to 38 months later or death whatever occurs first

13. Euro Quality of Life - 5D (EQ-5D) Index Scores in the ITT (Non-squamous) Population

    The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. These five health dimensions are summarized into a single score, the EQ-5D index score which ranges from -0.594 to 1 when the United Kingdom (UK) weights are applied (0=death, 1=perfect health). Higher index scores represent better health states.

    Time frame: from randomization of the first patient until 38 months later or death whatever occurs first

14. EQ-5D Visual Analog Scale (VAS) Scores in the ITT (Non-squamous) Population

    The EQ-5D also contains a visual analog scale (EQ-VAS), which records the respondent's self-rated health status on a vertical graduated visual analog scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).

    Time frame: from randomization of the first patient until 38 months later or death whatever occurs first

Baseline characteristics

Publications

• Paz-Ares LG, Biesma B, Heigener D, von Pawel J, Eisen T, Bennouna J, Zhang L, Liao M, Sun Y, Gans S, Syrigos K, Le Marie E, Gottfried M, Vansteenkiste J, Alberola V, Strauss UP, Montegriffo E, Ong TJ, Santoro A; NSCLC [non-small-cell lung cancer] Research Experience Utilizing Sorafenib (NExUS) Investigators Study Group. Phase III, randomized, double-blind, placebo-controlled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer. J Clin Oncol. 2012 Sep 1;30(25):3084-92. doi: 10.1200/JCO.2011.39.7646. Epub 2012 Jul 30. PubMed 22851564 ↗

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