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

Primary Purpose

Carcinoma, Non-Small-Cell Lung

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Sorafenib (Nexavar, BAY43-9006)

Placebo

About this trial

This is an interventional treatment trial for Carcinoma focused on measuring Non-Small Cell Lung Cancer (NSCLC), Sorafenib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Sorafenib (Nexavar, BAY43-9006)

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Overall Survival

Overall survival (OS) was defined as the time from date of randomization to date of death due to any cause. Overall survival of subjects alive at the time of analysis will be censored at their last date of follow-up or database cut off date whichever came first.

Secondary Outcome Measures

Progression-free Survival

Progression-free survival (PFS) was defined as the time from date of randomization to date of first observed disease progression (radiological or clinical, whichever is earlier) or death due to any cause, if death occurs before progression is documented. Progressive Disease (PD) is defined as at least a 20% increase in the sum of longest diameter (LD) of measured lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Appearance of new lesions will also constitute progressive disease. In exceptional circumstances unequivocal progression of a non-measured lesion may be accepted as evidence of disease progression.

Disease Control

Disease control (DC) was defined as the proportion of patients whose best response was Complete Response [CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target)] or Partial Response [PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD] or Stable Disease [SD: steady state of disease which was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD)].

Objective Tumor Response

Objective tumor response was defined as the proportion of patients whose best response was Complete Response [CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target)] or Partial Response [PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD] over the whole duration of study.

Time to Progression

Time to progression (TTP) was defined as the time from date of randomization to date of first observed disease progression (radiological or clinical, whichever is earlier).

Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status

The EORTC QLQ-C15-PAL is an abbreviated 15-item version of the EORTC core quality of life questionnaire (EORTC QLQ-C30) developed for use in palliative care. The 'Global Health status' subscale consists of question 15 of the questionnaire. The score of 'Global Health status' ranges from 0 (very poor) to 100 (excellent). The change of score ranges from -100 (maximum degree of worsening) to 100 (maximum degree of improvement).

Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale

A clinically valid 13-item tool for assessing disease- and treatment-specific symptoms in lung cancer patients in clinical trials. The coughing subscale uses question 1 of the questionnaire. The scale ranges from 0 to 100. Higher score means higher level of symptomatology/problems. The change of score ranges from -100 (decrease in level of symptomatology/problems) to 100 (increase in level of symptomatology/problems).

Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea

A clinically valid 13-item tool for assessing disease- and treatment-specific symptoms in lung cancer patients in clinical trials. The dyspnea subscale uses questions 3, 4 and 5 of the questionnaire. The scale ranges from 0 to 100. Higher score means higher level of symptomatology/problems. The change of score ranges from -100 (decrease in level of symptomatology/problems) to 100 (increase in level of symptomatology/problems).

Mean Change From Baseline in EuroQol-5D (EQ-5D) - Index Score

The Euro-Qol 5D (EQ-5D) is a validated assessment tool of Health Related Quality of Life (HRQOL) and utilities consisting of 15 statements. Patients select those statements that best describe their current health state regarding mobility, self-care, usual activities, pain/discomfort, and anxiety/depression which is converted into a utility value. Range of scale is from -0.594 (worst possible health state) to 1 (perfect health) based on UK weights. The change of score ranges from -1.594 (high degree of worsening) to 1.594 (high degree of improvement).

Mean Change From Baseline in EuroQol-5D (EQ-5D) - VAS Score

A visual analogue scale (EQ VAS) used by patients to rate their current health state from 100 (best imaginable health state) to 0 (worst imaginable health state). The change of score ranges from -100 (high degree of worsening) to 100 (high degree of improvement)

Full Information

NCT ID

NCT00863746

First Posted

March 17, 2009

Last Updated

January 7, 2015

Sponsor

Bayer

1. Study Identification

Unique Protocol Identification Number

NCT00863746

Brief Title

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

Acronym

MISSION

Official Title

A Phase III, Multi-center, Placebo-Controlled Trial of Sorafenib (BAY43-9006) in Patients With Relapsed or Refractory Advanced Predominantly Non Squamous Non-Small Cell Lung Cancer (NSCLC) After 2 or 3 Previous Treatment Regimens for Advanced Disease

Study Type

Interventional

2. Study Status

Record Verification Date

January 2015

Overall Recruitment Status

Completed

Study Start Date

April 2009 (undefined)

Primary Completion Date

March 2012 (Actual)

Study Completion Date

April 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayer

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

Detailed 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma, Non-Small-Cell Lung

Keywords

Non-Small Cell Lung Cancer (NSCLC), Sorafenib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

703 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sorafenib (Nexavar, BAY43-9006)

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Sorafenib (Nexavar, BAY43-9006)

Intervention Description

Sorafenib 400 mg twice daily (BID)

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo - 2 tablets twice daily (BID)

Primary Outcome Measure Information:

Title

Overall Survival

Description

Time Frame

From randomization of the first subject until 36 months later

Secondary Outcome Measure Information:

Title

Progression-free Survival

Description

Time Frame

From randomization of the first subject until 36 months later assessed every 6 weeks

Title

Disease Control

Description

Time Frame

From randomization of the first subject until 36 months later assessed every 6 weeks

Title

Objective Tumor Response

Description

Time Frame

From randomization of the first subject until 36 months later assessed every 6 weeks

Title

Time to Progression

Description

Time to progression (TTP) was defined as the time from date of randomization to date of first observed disease progression (radiological or clinical, whichever is earlier).

Time Frame

From randomization of the first subject until 36 months later assessed every 6 weeks

Title

Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status

Description

Time Frame