A 3rd/4th Line Placebo-controlled Trial of Sorafenib in Patients With Predominantly Non Squamous Non-Small Cell Lung Cancer (NSCLC). (MISSION)

Bayer

Status and phase: Completed; Phase 3

Conditions: Non-Small-Cell Lung; Carcinoma

Treatments: Drug: Placebo; Drug: Sorafenib (Nexavar, BAY43-9006)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00863746

2008-006914-62 (EudraCT Number)

13266

Details and patient eligibility

About

The purpose of the study is to see if sorafenib plus best supportive care (i.e. in addition to the non-cancer treatments patients would normally receive) is an effective treatment for lung cancer compared to best supportive care alone. The safety and tolerability of the two treatment groups will also be compared. The goal of the study is to test the ability of sorafenib to improve survival compared to best supportive care alone.

Full description

Acronyms used in Adverse Events section: Disseminated intravascular coagulation (DIC), International normalized ratio (INR), Atrioventricular (AV), Gastrointestinal (GI), Not otherwise specified (NOS), Common Terminology Criteria for Adverse Events (CTCAE), Absolute neutrophil count (ANC), Central nervous system (CNS), Acute respiratory distress syndrome (ARDS), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST).

Enrollment: 703 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Ability to understand and willingness to sign a written Informed Consent

• Advanced relapsed or refractory predominantly non squamous NSCLC. The diagnosis must have been confirmed cyto-/ histologically

• Patients must have measurable or non-measurable disease

• At least two but not more than three prior standard treatment regimens for NSCLC

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

• Male or female subjects >/= 18 years of age (>/=20 for Japan) at the time of Informed Consent

• Life expectancy of at least 12 weeks

• Ability to swallow oral medication

• Both men and women using adequate barrier birth control measures during the course of the trial and 4 weeks after the completion of trial

• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of the study drug:

  • Haemoglobin > 9.0 g/dl
  • Absolute neutrophil count (ANC) >1,500/mm3
  • Platelet count >/= 100,000/µl
  • Total bilirubin </=1.5 x the upper limit of normal
  • Alanine aminotransferase (ALT) < 2.5 x upper limit of normal (</= 5 x upper limit of normal in patients with liver metastases) Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (</= 5 x upper limit of normal in patients with liver metastases)
  • Alkaline phosphatase < 4 x upper limit of normal (</= 5 x upper limit of normal in patients with liver metastases)
  • Prothrombin Time (PT)-International Normalized Ratio (INR) or Partial Thromboplastin Time (PTT) < 1.5 x upper limit of normal
  • Serum creatinine < 1.5 x upper limit of normal
  • Calculated creatinine clearance of >/= 50 mL/min

Exclusion criteria

• NSCLC patients with predominantly squamous cell carcinoma histology

Excluded medical conditions:

• History of cardiac disease: Congestive heart failure, Active coronary artery disease (CAD), Cardiac arrhythmias (>Grade 2 NCI-CTCAE [National Cancer Institute-Common Terminology Criteria for Adverse Events] vers. 3.0)
• Uncontrolled hypertension despite two anti-hypertensive medications
• History of Human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
• History of organ allograft
• Active clinically serious infections (> grade 2 NCI-CTCAE vers. 3.0)
• Patients with seizure disorder requiring medication
• Patients with evidence or history of bleeding diathesis or coagulopathy
• Patients undergoing renal dialysis
• Pulmonary hemorrhage/ bleeding event >/= CTCAE grade 2 within four weeks prior to the first dose of the study drug
• Any other hemorrhage/ bleeding event >/= CTCAE grade 3 within four weeks prior to the first dose of the study drug
• Thrombotic or embolic venous or arterial events such as cerebrovascular accident
• Pregnant or breast-feeding women.
• Any condition which could affect the absorption or pharmacokinetics of the study drug
• Prior treatment with other Vascular Endothelial Growth Factor (VEGF) (R) inhibitors, including compounds that impact vascularity (i.e. sunitinib, thalidomide, vandetanib, vascular disrupting agents [VDA], VEGF-trap and other experimental agents of this class). Only bevacizumab (Avastin) is permitted.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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703 participants in 2 patient groups, including a placebo group

Sorafenib (Nexavar, BAY43-9006)

Experimental group

Description:

Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)

Treatment:

Drug: Sorafenib (Nexavar, BAY43-9006)

Placebo

Placebo Comparator group

Description:

Participants received 2 tablets of placebo orally twice daily (BID)

Treatment:

Drug: Placebo