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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00558636




Registration number
NCT00558636
Ethics application status
Date submitted
9/11/2007
Date registered
15/11/2007
Date last updated
27/12/2013

Titles & IDs
Public title
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)
Scientific title
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)
Secondary ID [1] 0 0
12621
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Non-Small-Cell Lung 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sorafenib + Paclitaxel + Carboplatin
Treatment: Drugs - Placebo + Paclitaxel + Carboplatin

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.

Placebo comparator: 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


Treatment: Drugs: 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.

Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival
Timepoint [1] 0 0
Up to 5 months after randomization of the first patient
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to 5 months after randomization of the first patient
Secondary outcome [2] 0 0
Best Tumor Response (Number of Responses Per Category) According to Response Evaluation Criteria in Solid Tumors (RECIST)
Timepoint [2] 0 0
Best tumor response assessed every 6 weeks by investigator during treatment up to 5 months after randomization of the first patient.
Secondary outcome [3] 0 0
Duration of Response
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
Change From Baseline of Lung Cancer Symptoms (LCS) Score Assessed at Each Treatment Cycle (21 Days Per Cycle) Starting With Cycle 2
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Change From Baseline of Health-Related Quality of Life (HRQoL) Score Assessed at Treatment Cycle 3 and Cycle 5
Timepoint [5] 0 0
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.
Secondary outcome [6] 0 0
Change From Baseline of Health-Related Quality of Life (HRQoL) Score Assessed at Treatment Cycle 7
Timepoint [6] 0 0
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.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2008
Sample size
Target
Accrual to date
Final
91
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
China
State/province [1] 0 0
Guangdong
Country [2] 0 0
China
State/province [2] 0 0
Hong Kong
Country [3] 0 0
China
State/province [3] 0 0
Jiangsu

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00558636
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00558636