Back to resultsStudy of Low Dose Chemotherapy Plus Sorafenib as Initial Therapy for Patients With Advanced Non-Squamous Cell NSCLC
Primary Purpose
Non Squamous Cell Lung Cancer, Non Small Cell Lung Cancer
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Docetaxel + Sorafenib
Sponsored by
About this trial
This is an interventional treatment trial for Non Squamous Cell Lung Cancer focused on measuring Docetaxel, Sorafenib
Eligibility Criteria
Inclusion Criteria:
- Pathologic-proven non-squamous cell-NSCLC
- Advanced non-squamous-NSCLC: Stage IIIB with pleural effusion or stage IV, or recurrent disease
- Eastern Cooperative Oncology Group (ECOG) Performance Status 2: In bed less than 50% of the time, unable to work, but able to care for self
- Measurable or non-measurable disease as defined by solid tumor response criteria (RECIST)
- No prior systemic chemotherapy or biologic therapy
- Age greater than or equal to 19 years old (Note: State of Alabama requirement)
Adequate bone marrow and renal function as assessed by the following:
- Hemoglobin greater than or equal to 9.0 g/dL
- Absolute neutrophil count (ANC)greater than or equal to 1500/mm3
- Platelet count greater than or equal to 100,000/mm3
- Creatinine less than or equal to 1.5 times upper limit of normal (ULN)
Hepatic function requirements
- Total bilirubin less than or equal to ULN
- AST and ALT and alkaline phosphatase must be within the range allowing for eligibility. In determining eligibility the more abnormal of the two values (AST and ALT) should be used
- Women of childbearing potential must have a negative serum pregnancy test performed within 72 hours prior to the start of treatment.
Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation.
Men should use adequate birth control for at least three months after the last administration of sorafenib.
- 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.
- International normalized ratio (INR) less than or equal to 1.5 or a prothrombin time/partial prothrombin time (PT/PTT) within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
Exclusion Criteria:
- Predominant squamous cell histology will be excluded
- Cardiac disease: Congestive heart failure greater than class II New York Heart Association (NYHA). Patents 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 must undergo a CT scan/MRI of the brain to exclude brain metastasis.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic pressure greater than 90 mmHg, despite optimal medical management.
- Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
- Active clinically serious infection greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 2.
- Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
- History of significant hemoptysis (defined as bright red blood of a ½ teaspoon or more). Patients with blood-tinged or blood-streaked sputum will be permitted on study if the hemoptysis amount to less than 5 mL of blood per episode and less than 10 mL of blood per 24 hour period.
- Any other hemorrhage/bleeding event greater than or equal to 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 study drug.
- Use of St. John's Wort or rifampin (rifampicin).
- Known or suspected allergy to sorafenib or any agent given in the course of this trial.
- Any condition that impairs patient's ability to swallow whole pills.
- Any malabsorption problem.
- History of severe hypersensitivity reaction to any drugs formulated with polysorbate 80.
- Women who are breast-feeding.
Sites / Locations
- University of Alabama at Birmingham
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Metronomic Docetaxel + Sorafenib
Arm Description
Subjects with advanced non-squamous cell non-small cell lung cancer with poor performance status will receive treatment in this non-randomized, open-label Phase II Study of Metronomic Chemotherapy (docetaxel) plus sorafenib as first-line therapy. Subjects will be treated with metronomic chemotherapy with low dose docetaxel weekly for 3 out of 4 weeks, and sorafenib will be administered continuously 400 mg bid on a 28 day cycle. Treatment with metronomic chemotherapy will be expressed as a 4-week cycle.
Outcomes
Primary Outcome Measures
2-month Progression-free Survival Rate
Evaluation of the 2-month progression-free survival in poor performance status patients with non-squamous non-small cell lung cancer with the goal to improve 2-month progression free survival from 50% to 70%. The 2-month progression free survival is determined after 8 weeks on treatment. Those patients that had less than 20% increase in the tumor target lesions are considered as progression free survival. The primary endpoint is the percentage of patients that are progression free in 2 months.
Secondary Outcome Measures
Response Rate in Poor Performance Status Subjects
To assess response rate and tumor control rate (complete remission + partial remission + stable disease) in poor performance status (PS =2) patients with advanced or metastatic (Stage IIIB - pleural effusion/IV) non-squamous cell-NSCLC treated with metronomic chemotherapy plus sorafenib. The objective response was defined as a percentage of those patients that had 30% or more of tumor regression at any time during treatment. Tumor control rate include the percentage of those patients that have less than 20% increase in the target tumor parameters during treatment (stable disease + partial response + complete response).
Full Information
NCT ID
NCT00801801
First Posted
December 2, 2008
Last Updated
April 7, 2017
Sponsor
Francisco Robert,MD
Collaborators
Sanofi, Bayer
1. Study Identification
Unique Protocol Identification Number
NCT00801801
Brief Title
Study of Low Dose Chemotherapy Plus Sorafenib as Initial Therapy for Patients With Advanced Non-Squamous Cell NSCLC
Official Title
Pilot Phase IIa Study of Metronomic Chemotherapy With Taxotere (Docetaxel) Plus Nexavar (Sorafenib) as First-Line Therapy in Performance Status-2 Patients With Advanced Non-Squamous Cell Non-Small Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Terminated
Why Stopped
Sponsors withdrew funding; preliminary efficacy data was not encouraging.
Study Start Date
January 2008 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
March 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Francisco Robert,MD
Collaborators
Sanofi, Bayer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess the 2-month progression-free survival in patients with advanced or metastatic, non-squamous cell lung cancer treated with weekly low dose docetaxel in combination with a biologic dose of sorafenib.
Detailed Description
The median survival of untreated advanced stage NSCLC is 5-6 months (2,3). Patients with poor performance status due to malignancy or co-morbidities have a poorer survival. This group of patients is underrepresented in clinical trials and may not receive chemotherapy due to fear of increased toxicities with systemic chemotherapy. The overall median survival of patients with advanced NSCLC treated with first-line platinum-based doublets is less than 12 months (8 10 months) with a 1-year and 2-year survival rate of 33% and 11%, respectively (4 6). No chemotherapy regimen has a significant advantage over the others in the treatment of advanced NSCLC. Agents targeting epidermal growth factor receptor, matrix metalloproteinase, farnesyl transferase, protein kinase C and retinoic X receptor have so far shown no survival benefit in combination with chemotherapy in advanced NSCLC (7-13). Docetaxel has activity in NSCLC in both first line and second line settings. In poor performance status patients or elderly patients, single agent chemotherapy is recommended. Weekly docetaxel administration is well tolerated and has lesser incidence of hematologic toxicity with no difference in overall survival when compared to patients receiving higher doses (75 mg/m2) q 3 weeks (14-18). There is an increased need for better strategies to improve survival as well as reduce regimen related toxicity for this large group of patients. The use of targeted therapy as well as low dose-protracted chemotherapy (metronomic chemotherapy) needs evaluation as such therapies have a better toxicity profile.
Sorafenib (BAY 49-bursts of toxic maximum tolerated dose (MTD) chemotherapy interspersed with long breaks, there is now a shift in thinking towards the view that more compressed or accelerated schedules of drug administration using much smaller individual doses than the MTD would be more effective; not only in terms of reducing certain toxicities, but perhaps even in improving antitumor effect as well. Moreover, some of these dosing/scheduling strategies are ideally suited to combining chemotherapeutic agents with many of the new targeted biologic drugs. The most recent refinement of this concept is called "metronomic" chemotherapy, which refers to the frequent administration of cytotoxic chemotherapeutic agents at doses significantly below the MTD, with no prolonged drug-free breaks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Squamous Cell Lung Cancer, Non Small Cell Lung Cancer
Keywords
Docetaxel, Sorafenib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Metronomic Docetaxel + Sorafenib
Arm Type
Experimental
Arm Description
Subjects with advanced non-squamous cell non-small cell lung cancer with poor performance status will receive treatment in this non-randomized, open-label Phase II Study of Metronomic Chemotherapy (docetaxel) plus sorafenib as first-line therapy.
Subjects will be treated with metronomic chemotherapy with low dose docetaxel weekly for 3 out of 4 weeks, and sorafenib will be administered continuously 400 mg bid on a 28 day cycle. Treatment with metronomic chemotherapy will be expressed as a 4-week cycle.
Intervention Type
Drug
Intervention Name(s)
Docetaxel + Sorafenib
Other Intervention Name(s)
Taxotere (Docetaxel), Nexavar (Sorafenib)
Intervention Description
Subjects will be treated with metronomic chemotherapy with low dose docetaxel weekly for 3 out of 4 weeks, and sorafenib will be administered continuously 400 mg bid on a 28 day cycle. Treatment with metronomic chemotherapy will be expressed as a 4-week cycle. Tumor response to treatment will be evaluated after every 8 weeks. Treatment with metronomic chemotherapy and sorafenib will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with sorafenib will then continue until disease progression, intolerable toxicity or withdrawal of consent.
Primary Outcome Measure Information:
Title
2-month Progression-free Survival Rate
Description
Evaluation of the 2-month progression-free survival in poor performance status patients with non-squamous non-small cell lung cancer with the goal to improve 2-month progression free survival from 50% to 70%. The 2-month progression free survival is determined after 8 weeks on treatment. Those patients that had less than 20% increase in the tumor target lesions are considered as progression free survival. The primary endpoint is the percentage of patients that are progression free in 2 months.
Time Frame
Baseline to 2 months
Secondary Outcome Measure Information:
Title
Response Rate in Poor Performance Status Subjects
Description
To assess response rate and tumor control rate (complete remission + partial remission + stable disease) in poor performance status (PS =2) patients with advanced or metastatic (Stage IIIB - pleural effusion/IV) non-squamous cell-NSCLC treated with metronomic chemotherapy plus sorafenib. The objective response was defined as a percentage of those patients that had 30% or more of tumor regression at any time during treatment. Tumor control rate include the percentage of those patients that have less than 20% increase in the target tumor parameters during treatment (stable disease + partial response + complete response).
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pathologic-proven non-squamous cell-NSCLC
Advanced non-squamous-NSCLC: Stage IIIB with pleural effusion or stage IV, or recurrent disease
Eastern Cooperative Oncology Group (ECOG) Performance Status 2: In bed less than 50% of the time, unable to work, but able to care for self
Measurable or non-measurable disease as defined by solid tumor response criteria (RECIST)
No prior systemic chemotherapy or biologic therapy
Age greater than or equal to 19 years old (Note: State of Alabama requirement)
Adequate bone marrow and renal function as assessed by the following:
Hemoglobin greater than or equal to 9.0 g/dL
Absolute neutrophil count (ANC)greater than or equal to 1500/mm3
Platelet count greater than or equal to 100,000/mm3
Creatinine less than or equal to 1.5 times upper limit of normal (ULN)
Hepatic function requirements
Total bilirubin less than or equal to ULN
AST and ALT and alkaline phosphatase must be within the range allowing for eligibility. In determining eligibility the more abnormal of the two values (AST and ALT) should be used
Women of childbearing potential must have a negative serum pregnancy test performed within 72 hours prior to the start of treatment.
Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation.
Men should use adequate birth control for at least three months after the last administration of sorafenib.
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.
International normalized ratio (INR) less than or equal to 1.5 or a prothrombin time/partial prothrombin time (PT/PTT) within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
Exclusion Criteria:
Predominant squamous cell histology will be excluded
Cardiac disease: Congestive heart failure greater than class II New York Heart Association (NYHA). Patents 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 must undergo a CT scan/MRI of the brain to exclude brain metastasis.
Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic pressure greater than 90 mmHg, despite optimal medical management.
Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
Active clinically serious infection greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 2.
Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
History of significant hemoptysis (defined as bright red blood of a ½ teaspoon or more). Patients with blood-tinged or blood-streaked sputum will be permitted on study if the hemoptysis amount to less than 5 mL of blood per episode and less than 10 mL of blood per 24 hour period.
Any other hemorrhage/bleeding event greater than or equal to 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 study drug.
Use of St. John's Wort or rifampin (rifampicin).
Known or suspected allergy to sorafenib or any agent given in the course of this trial.
Any condition that impairs patient's ability to swallow whole pills.
Any malabsorption problem.
History of severe hypersensitivity reaction to any drugs formulated with polysorbate 80.
Women who are breast-feeding.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francisco Robert, M.D.
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294 - 0104
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of Low Dose Chemotherapy Plus Sorafenib as Initial Therapy for Patients With Advanced Non-Squamous Cell NSCLC
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