Non Squamous Cell Lung CancerPhase 2NCT00801801
Study of Low Dose Chemotherapy Plus Sorafenib as Initial Therapy for Patients With Advanced Non-Squamous Cell NSCLC
A Phase 2 study testing Docetaxel + Sorafenib in people with Non Squamous Cell Lung Cancer and Non Small Cell Lung Cancer, run by Francisco Robert,MD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Non Squamous Cell Lung Cancer, Non Small Cell Lung Cancer
- What is being tested?
- Docetaxel + Sorafenib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2008to Mar 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294 - 0104
About this study
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
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.
Read the 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.
- Being tested
- Docetaxel + Sorafenib
- Keywords
- Docetaxel, Sorafenib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Docetaxel + SorafenibDrug
Also called Taxotere (Docetaxel), Nexavar (Sorafenib)
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.
| Study group | Role | What they receive |
|---|---|---|
| Metronomic Docetaxel + Sorafenib | Experimental | 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. Receives: Drug: Docetaxel + Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 2 months
Secondary outcomes (1)
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).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2008 (estimated)
- Study startJan 2008
- Primary completionOct 2009
- Study completionMar 2011
Why it stopped: Sponsors withdrew funding; preliminary efficacy data was not encouraging.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non Squamous Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Francisco Robert,MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Francisco Robert,MD, University of Alabama at Birmingham
- Investigators
- Francisco Robert, M.D., Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00801801
- Sponsor's protocol ID
- F080703006
- Other IDs
- UAB 0750
- Status last verified
- Apr 2017
- First submitted
- 2 Dec 2008
- Last updated
- 17 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00801801
- Acronym / sponsor ID
- F080703006
- Keywords
- Docetaxel, Sorafenib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsors withdrew funding; preliminary efficacy data was not encouraging.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Francisco Robert,MDUniversity, hospital or other
- Collaborators
- Sanofi, Bayer
- Study start
- Jan 2008
- Primary completion
- Oct 2009 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 4 Dec 2008 (estimated)
- Results
- Posted 19 Jun 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metronomic Docetaxel + Sorafenib | Experimental | Drug: Docetaxel + SorafenibSubjects 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. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Docetaxel + SorafenibAlso: Taxotere (Docetaxel), Nexavar (Sorafenib)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. | Drug | Metronomic Docetaxel + Sorafenib |
Primary outcome
2-month Progression-free Survival Rate
Time frame: Baseline to 2 months
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.
1 secondary outcome
Response Rate in Poor Performance Status Subjects
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francisco Robert, M.D. principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Docetaxel + Sorafenib in people with Non Squamous Cell Lung Cancer and Non Small Cell Lung Cancer, run by Francisco Robert,MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
2-month Progression-free Survival Rate (time frame: Baseline to 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2017.