A Trial Comparing Safety and Efficacy of Carboplatin and Paclitaxel Plus or Minus Sorafenib (BAY43-9006) in Chemonaive Patients With Stage IIIB-IV Non-Small Cell Lung Cancer (NSCLC)
2. Dezember 2013 aktualisiert von: Bayer
A Randomized Controlled Trial Comparing Safety and Efficacy of Carboplatin and Paclitaxel Plus or Minus Sorafenib (BAY43-9006) in Chemonaive Patients With Stage IIIB-IV Non-Small Cell Lung Cancer (NSCLC)
The purpose of this study conducted in Asia-Pacific was to evaluate the efficacy and safety of Sorafenib in combination with paclitaxel and carboplatin versus placebo in combination with paclitaxel and carboplatin for chemonaive patients with unresectable stage IIIB (with effusion) or stage IV NSCLC.
However, as indicated below, the study was terminated prematurely when the results from Study 11961 (NCT00300885), an earlier Phase 3 study of similar design in subjects with advanced NSCLC, showed an overall lack of efficacy and increased mortality in subjects with squamous subtype.
The data available is presented as descriptive analyses, due to the limitations of implementing the statistical analysis plan.
Studienübersicht
Status
Beendet
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
The study was terminated early when the results from Study 11961 (NCT00300885), an earlier Phase 3 study evaluating the effects of Sorafenib in combination with paclitaxel and carboplatin in subjects with advanced NSCLC, showed an overall lack of efficacy of Sorafenib in combination with paclitaxel and carboplatin in NSCLC and increased mortality in subjects with squamous subtype.
Studientyp
Interventionell
Einschreibung (Tatsächlich)
91
Phase
- Phase 3
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
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Beijing, China, 100730
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Beijing, China, 100021
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Beijing, China, 100142
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Chongqing, China, 400038
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Shanghai, China, 200032
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Shanghai, China, 200433
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Guangdong
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Guangzhou, Guangdong, China, 510060
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Guangzhou, Guangdong, China, 510515
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Hong Kong
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Shatin, Hong Kong, China
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Jiangsu
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Nanjing, Jiangsu, China, 210003
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Zhejiang
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Hangzhou, Zhejiang, China, 310016
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Hangzhou, Zhejiang, China, (310022),
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New- Delhi, Indien, 110008
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Maharashtra
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Mumbai, Maharashtra, Indien, 400012
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Gyeonggi-do, Korea, Republik von, 410-769
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Seoul, Korea, Republik von, 136-705
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Singapore, Singapur, 119228
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Singapore, Singapur, 169610
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Changhua, Taiwan, 500
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Taipei, Taiwan, 100
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Bangkok, Thailand
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Bangkok, Thailand, 10330
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Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre und älter (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Beschreibung
Inclusion Criteria:
- Stage IIIB (with cytologically confirmed malignant pleural or pericardial effusion) or Stage IV histological or cytological confirmation of NSCLC (thoracentesis or pericardiocentesis is not necessary if a biopsy of the original tumor is available to confirm diagnosis of NSCLC)
- Patients must have measurable disease according to response evaluation criteria in solid tumors (RECIST) criteria
- Prior local radiotherapy is allowed if it is completed at least 3 weeks prior to the first dose of study drug, but the lesion which undergo RECIST assessment should not be in the field of the prior radiation
- Prior surgery is allowed if it is performed at least 4 weeks prior to the first dose of study drug
- 18 years and above
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Life expectancy of at least 12 weeks
- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of first dose:
- Hemoglobin 9.0 g/dl
- Absolute neutrophil count (ANC) 1,500/mm3
- Platelet count 100,000/mm3
- Total bilirubin < 1.5 times the upper limit of normal
- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement)
- international normalized ratio (INR) < 1.5 and activated or adjusted partial thromboplastin time (APTT) within normal limits (1.2 times the lower limit of normal (LLN) to 1.2 times the upper limit of normal (ULN))
- Creatinine </= 1.5 times the upper limit of normal
- Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures
Exclusion Criteria:
- Any prior systemic anticancer therapy including cytotoxic therapy, targeted agents, experimental therapy, adjuvant, or neo-adjuvant therapy for any current or prior diagnosis of NSCLC
- Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new-onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
- Known brain metastasis. Patients with neurological symptoms should undergo at Computed Tomography (CT) scan/Magnetic Resonance Imaging (MRI) of the brain to exclude brain metastasis
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic pressure > 90 mm Hg, despite optimal medical management
- Known human immunodeficiency virus (HIV) infection
- Active clinically serious infections > Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
- Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months
- Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug
- Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug
- Serious, non-healing wound, ulcer, or bone fracture
- Evidence or history of bleeding diathesis or coagulopathy
- Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug
- Therapeutic anticoagulation with vitamin K antagonists such as warfarin, or with heparins or heparinoids. Low dose warfarin (1 mg daily, oral) is permitted if the INR remains < 1.5. Low-dose aspirin is permitted
- Known or suspected allergy to sorafenib or any agent given in the course of this trial
- Cancer other than NSCLC within 5 years prior to start of study treatment, EXCEPT cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumors
- Concurrent cancer that is distinct in primary site or histology from NSCLC
- Substance abuse, medical, psychological or social conditions that may interfere with the patients participation in the study or evaluation of the study results
- Any condition that impairs patients ability to swallow whole pills
- Any malabsorption condition
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
- Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation, including the 30 days period after last study drug dosing. The investigator should advise the patient how to achieve an adequate contraception
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Verdreifachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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Experimental: Sorafenib + Paclitaxel + Carboplatin
Chemotherapy plus Multi Kinase Inhibitor: Sorafenib Group - Sorafenib (Nexavar, BAY43-9006), [400 mg, (2 tablets x 200 mg each) orally, twice daily] on Study Days 2-19 and paclitaxel (175 mg/m^2, intravenous (IV), over 2.5 to 4 hours) and carboplatin (area under the curve (AUC) =5, IV for 15 to 60 minutes) on Study Day 1.
The cycle duration will be 21 days.
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Chemotherapy plus Multi Kinase Inhibitor: Sorafenib Group - Sorafenib (Nexavar, BAY43-9006), [400 mg, (2 tablets x 200 mg each) orally, twice daily] on Study Days 2-19 and paclitaxel (175 mg/m^2, intravenous (IV), over 2.5 to 4 hours) and carboplatin (area under the curve (AUC) =5, IV for 15 to 60 minutes) on Study Day 1.
The cycle duration will be 21 days.
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Placebo-Komparator: Placebo + Paclitaxel + Carboplatin
Chemotherapy + Placebo: Placebo Group - Placebo (2 tablets twice daily, orally) on Study Days 2-19 and paclitaxel (175 mg/m^2 IV, over 2.5 to 4 hours) and carboplatin (AUC=5 IV, for 15 to 60 minutes) on Study Day 1.
The cycle duration will be 21 days
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Chemotherapy + Placebo: Placebo Group - Placebo (2 tablets twice daily, orally) on Study Days 2-19 and paclitaxel (175 mg/m^2 IV, over 2.5 to 4 hours) and carboplatin (AUC=5 IV, for 15 to 60 minutes) on Study Day 1.
The cycle duration will be 21 days
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Progression Free Survival
Zeitfenster: Up to 5 months after randomization of the first patient
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Progression free survival (PFS) is the time (days) from date of randomization to date of first observed disease progression (radiological or clinical, whichever was earlier) or death due to any cause, if death occurred before progression was documented.
Since the study was terminated early and 89% of subjects' data were censored, only the number of PFS events (Failed [progressed or died before progression]) is reported, not the usual measure "number of days".
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Up to 5 months after randomization of the first patient
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Overall Survival (OS)
Zeitfenster: Up to 5 months after randomization of the first patient
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Overall survival is the number of days from the date of randomization to the date of death due to any cause.
Subjects alive at the time of analysis were censored at their last date of follow-up.
Since the study was terminated early and 89% of subjects' data were censored, only the number of subjects who Failed (died) or were Censored is reported, not the usual measure "number of days".
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Up to 5 months after randomization of the first patient
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Best Tumor Response (Number of Responses Per Category) According to Response Evaluation Criteria in Solid Tumors (RECIST)
Zeitfenster: Best tumor response assessed every 6 weeks by investigator during treatment up to 5 months after randomization of the first patient.
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Complete response (CR): Disappearance of all target lesions (TL).
Partial response (PR): At least 30% decrease in sum of the largest diameter (LD) of TLs, taking baseline sum as reference.
Stable disease (SD): No change in tumor size.
Progressive disease (PD): At least a 20% increase in the sum of the LD of TLs, taking as reference the smallest sum LD recorded since treatment started, or the appearance of 1 or more new lesions.
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Best tumor response assessed every 6 weeks by investigator during treatment up to 5 months after randomization of the first patient.
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Duration of Response
Zeitfenster: Time from first documented objective response (complete response or partial response) to disease progression or death, or to last tumor assessment if censored, up to 5 months after randomization of the first patient.
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Duration of response (PR or better) was defined as the time from the first documented objective PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented).
Since only 4 subjects had a response, the duration of response was not calculated.
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Time from first documented objective response (complete response or partial response) to disease progression or death, or to last tumor assessment if censored, up to 5 months after randomization of the first patient.
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Change From Baseline of Lung Cancer Symptoms (LCS) Score Assessed at Each Treatment Cycle (21 Days Per Cycle) Starting With Cycle 2
Zeitfenster: Change from baseline of LCS score assessed at each treatment cycle starting with Cycle 2 (Cycles 2, 3, 4, 5, 6, 7; 21 days per cycle) up to 5 months after randomization of the first patient.
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The LCS is a validated instrument for determining treatment impact on lung symptoms.
The LCS consists of 7 questions with 5 responses ranging from "not at all" to "very much".
The LCS total score ranges from 0 to 28.
Lower scores reflect greater lung cancer symptoms.
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Change from baseline of LCS score assessed at each treatment cycle starting with Cycle 2 (Cycles 2, 3, 4, 5, 6, 7; 21 days per cycle) up to 5 months after randomization of the first patient.
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Change From Baseline of Health-Related Quality of Life (HRQoL) Score Assessed at Treatment Cycle 3 and Cycle 5
Zeitfenster: Change from baseline of HRQoL score assessed (at treatment Cycle 3 and Cycles 5 [21 days per cycle]) up to 5 months after randomization of the first patient.
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HRQoL was assessed with the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire, a validated instrument for determining lung cancer HRQoL.
The 36-item questionnaire includes 4 domains: Physical, functional, emotional, and social/family well-being, and a lung cancer-specific subscale.
The FACT-L total score ranges from 1 to 136.
Lower scores demonstrate impaired HRQoL.
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Change from baseline of HRQoL score assessed (at treatment Cycle 3 and Cycles 5 [21 days per cycle]) up to 5 months after randomization of the first patient.
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Change From Baseline of Health-Related Quality of Life (HRQoL) Score Assessed at Treatment Cycle 7
Zeitfenster: Change from baseline of HRQoL score assessed (at treatment Cycle 7 [21 days per cycle]) up to 5 months after randomization of the first patient.
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HRQoL was assessed with the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire, a validated instrument for determining lung cancer HRQoL.
The 36-item questionnaire includes 4 domains: Physical, functional, emotional, and social/family well-being, and a lung cancer-specific subscale.
The FACT-L total score ranges from 1 to 136.
Lower scores demonstrate impaired HRQoL.
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Change from baseline of HRQoL score assessed (at treatment Cycle 7 [21 days per cycle]) up to 5 months after randomization of the first patient.
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Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn
1. September 2007
Primärer Abschluss (Tatsächlich)
1. Mai 2008
Studienabschluss (Tatsächlich)
1. Mai 2008
Studienanmeldedaten
Zuerst eingereicht
9. November 2007
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
14. November 2007
Zuerst gepostet (Schätzen)
15. November 2007
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
27. Dezember 2013
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
2. Dezember 2013
Zuletzt verifiziert
1. Dezember 2013
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen der Atemwege
- Neubildungen
- Lungenkrankheit
- Neubildungen nach Standort
- Neubildungen der Atemwege
- Thoraxneoplasmen
- Karzinom, bronchogen
- Bronchiale Neubildungen
- Lungentumoren
- Karzinom, nicht-kleinzellige Lunge
- Molekulare Mechanismen der pharmakologischen Wirkung
- Enzym-Inhibitoren
- Antineoplastische Mittel
- Tubulin-Modulatoren
- Antimitotische Mittel
- Mitose-Modulatoren
- Antineoplastische Mittel, Phytogen
- Proteinkinase-Inhibitoren
- Carboplatin
- Paclitaxel
- Sorafenib
- Albumingebundenes Paclitaxel
Andere Studien-ID-Nummern
- 12621
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