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)

NCT00558636 | Terminated Phase 3 Results DMC

• 1 other identifier: 12621
• Study Type: interventional
• Target: 91
• Locations: 6 countries
• Sites: 22

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  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 Outcomes (6)

• Overall Survival (OS)

  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)

  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 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

  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

  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.

Study Arms (2)

Sorafenib + Paclitaxel + Carboplatin

EXPERIMENTAL

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

Placebo + Paclitaxel + Carboplatin

PLACEBO COMPARATOR

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

Interventions

Sorafenib + Paclitaxel + Carboplatin DRUG

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.

Sorafenib + Paclitaxel + Carboplatin

Placebo + Paclitaxel + Carboplatin DRUG

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

Placebo + Paclitaxel + Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (22)

Unknown Facility

Guangzhou, Guangdong, 510060, China

Location

Unknown Facility

Guangzhou, Guangdong, 510515, China

Location

Unknown Facility

Shatin, Hong Kong, China

Location

Unknown Facility

Nanjing, Jiangsu, 210003, China

Location

Unknown Facility

Hangzhou, Zhejiang, (310022),, China

Location

Unknown Facility

Hangzhou, Zhejiang, 310016, China

Location

Unknown Facility

Beijing, 100021, China

Location

Unknown Facility

Beijing, 100142, China

Location

Unknown Facility

Beijing, 100730, China

Location

Unknown Facility

Chongqing, 400038, China

Location

Unknown Facility

Shanghai, 200032, China

Location

Unknown Facility

Shanghai, 200433, China

Location

Unknown Facility

Mumbai, Maharashtra, 400012, India

Location

Unknown Facility

New Delhi, 110008, India

Location

Unknown Facility

Singapore, 119228, Singapore

Location

Unknown Facility

Singapore, 169610, Singapore

Location

Unknown Facility

Gyeonggi-do, 410-769, South Korea

Location

Unknown Facility

Seoul, 136-705, South Korea

Location

Unknown Facility

Taipei, Taiwan, 100, Taiwan

Location

Unknown Facility

Changhua, 500, Taiwan

Location

Unknown Facility

Bangkok, Bangkok, 10330, Thailand

Location

Unknown Facility

Bangkok, Bangkok, Thailand

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Sorafenib; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Coordination Complexes

Limitations and Caveats

Due to early termination of the study, no comparison of treatments was possible. This study also provided limited opportunity to distinguish between Adverse Events associated with sorafenib and events associated with the underlying lung disease.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2007
• First Posted: November 15, 2007
• Study Start: September 1, 2007
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: December 27, 2013
• Results First Posted: October 20, 2010

Record last verified: 2013-12

Locations

IN (2); TH (2); CN (12); SG (2); KR (2); TW (2)