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)

December 2, 2013 updated by: 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
91

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China, 100730
      • Beijing, China, 100021
      • Beijing, China, 100142
      • Chongqing, China, 400038
      • Shanghai, China, 200032
      • Shanghai, China, 200433
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
      • Guangzhou, Guangdong, China, 510515
    • Hong Kong
      • Shatin, Hong Kong, China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210003
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310016
      • Hangzhou, Zhejiang, China, (310022),
  • India
      • New- Delhi, India, 110008
    • Maharashtra
      • Mumbai, Maharashtra, India, 400012
  • Korea, Republic of
      • Gyeonggi-do, Korea, Republic of, 410-769
      • Seoul, Korea, Republic of, 136-705
  • Singapore
      • Singapore, Singapore, 119228
      • Singapore, Singapore, 169610
  • Taiwan
      • Changhua, Taiwan, 500
      • Taipei, Taiwan, 100
  • Thailand
      • Bangkok, Thailand
      • Bangkok, Thailand, 10330

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Drug: 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
Drug: 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: Up to 5 months after randomization of the first patient
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".
Up to 5 months after randomization of the first patient

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to 5 months after randomization of the first patient
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".
Up to 5 months after randomization of the first patient
Best Tumor Response (Number of Responses Per Category) According to Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: Best tumor response assessed every 6 weeks by investigator during treatment up to 5 months after randomization of the first patient.
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.
Best tumor response assessed every 6 weeks by investigator during treatment up to 5 months after randomization of the first patient.
Duration of Response
Time Frame: 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.
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.
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.
Change From Baseline of Lung Cancer Symptoms (LCS) Score Assessed at Each Treatment Cycle (21 Days Per Cycle) Starting With Cycle 2
Time Frame: 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.
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.
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.
Change From Baseline of Health-Related Quality of Life (HRQoL) Score Assessed at Treatment Cycle 3 and Cycle 5
Time Frame: 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.
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.
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.
Change From Baseline of Health-Related Quality of Life (HRQoL) Score Assessed at Treatment Cycle 7
Time Frame: 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.
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bayer

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2008

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2008

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 9, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 14, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 15, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 27, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 2, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 12621

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