Trial Outcomes & Findings for Lower Dose Chemotherapy Given More Frequent With Avastin to Treat Advanced Non-Squamous Non-Small Cell Lung Cancer (NCT NCT00655850)
NCT ID: NCT00655850
Last Updated: 2017-07-17
Results Overview
Progression Free Survival is defined as the number of days from the day the subject started treatment to the day the subject experiences disease progression in accordance with the Response Evaluation Criteria Solid Tumors (RECIST v1.0). The RECIST criteria indicates progression as a 20% increase in the total tumor measurement over nadir value or the appearance of new lesions.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
39 participants
Primary outcome timeframe
Baseline to 24 months
Results posted on
2017-07-17
Participant Flow
Protocol Open to Accrual: March 2008, Primary Completion Date: September 2015 and Study Completion Date: September 2016. Recruitment location: University of Alabama at Birmingham.
This study is being done to determine the overall progression-free survival (PFS) in patients with advanced or metastatic (Stage IIIB - pleural effusion/IV), non-squamous histology Non-Small Cell Lung Cancer (NSCLC) treated with metronomic chemotherapy plus Avastin.
Participant milestones
| Measure |
Paclitaxel and Gemcitabine + Avastin
Patients will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks which constitutes one cycle (4 weeks). Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will continue until disease progression, intolerable toxicity, or withdrawal of consent.
Paclitaxel: -Prior to receiving paclitaxel, all patients will receive the following premedications one hour before the infusion:
* Dexamethasone 20mg, intravenously (IV)
* Diphenhydramine 50 mg IV
* Ranitidine 50 mg IV
* Paclitaxel will be administered after the gemcitabine infusion as a 1 hour (IV) infusion
* The initial dose of paclitaxel is 80 mg/m2/weekly for 3 out of 4 weeks (Day 1, 8, 15)
Paclitaxel Dose Levels:
* Dose Level 1 \_\_\_\_\_\_\_\_80 mg/m2/weekly
* Dose Level -1 \_\_\_\_\_
|
|---|---|
|
Overall Study
STARTED
|
39
|
|
Overall Study
COMPLETED
|
36
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
Paclitaxel and Gemcitabine + Avastin
Patients will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks which constitutes one cycle (4 weeks). Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will continue until disease progression, intolerable toxicity, or withdrawal of consent.
Paclitaxel: -Prior to receiving paclitaxel, all patients will receive the following premedications one hour before the infusion:
* Dexamethasone 20mg, intravenously (IV)
* Diphenhydramine 50 mg IV
* Ranitidine 50 mg IV
* Paclitaxel will be administered after the gemcitabine infusion as a 1 hour (IV) infusion
* The initial dose of paclitaxel is 80 mg/m2/weekly for 3 out of 4 weeks (Day 1, 8, 15)
Paclitaxel Dose Levels:
* Dose Level 1 \_\_\_\_\_\_\_\_80 mg/m2/weekly
* Dose Level -1 \_\_\_\_\_
|
|---|---|
|
Overall Study
Death
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Lower Dose Chemotherapy Given More Frequent With Avastin to Treat Advanced Non-Squamous Non-Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Paclitaxel and Gemcitabine + Avastin
n=39 Participants
Patients will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks which constitutes one cycle (4 weeks). Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will continue until disease progression, intolerable toxicity, or withdrawal of consent.
Paclitaxel: -Prior to receiving paclitaxel, all patients will receive the following premedications one hour before the infusion:
* Dexamethasone 20mg, intravenously (IV)
* Diphenhydramine 50 mg IV
* Ranitidine 50 mg IV
* Paclitaxel will be administered after the gemcitabine infusion as a 1 hour (IV) infusion
* The initial dose of paclitaxel is 80 mg/m2/weekly for 3 out of 4 weeks (Day 1, 8, 15)
Paclitaxel Dose Levels:
* Dose Level 1 \_\_\_\_\_\_\_\_80 mg/m2/weekly
* Dose Level -1 \_\_\_\_\_
|
|---|---|
|
Age, Continuous
|
59.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
31 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
39 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 24 monthsPopulation: Participants with advanced chemotherapy naïve with non-squamous non-small cell lung cancer.
Progression Free Survival is defined as the number of days from the day the subject started treatment to the day the subject experiences disease progression in accordance with the Response Evaluation Criteria Solid Tumors (RECIST v1.0). The RECIST criteria indicates progression as a 20% increase in the total tumor measurement over nadir value or the appearance of new lesions.
Outcome measures
| Measure |
Paclitaxel and Gemcitabine + Avastin
n=36 Participants
Patients will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks which constitutes one cycle (4 weeks). Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will continue until disease progression, intolerable toxicity, or withdrawal of consent.
Paclitaxel: -Prior to receiving paclitaxel, all patients will receive the following premedications one hour before the infusion:
* Dexamethasone 20mg, intravenously (IV)
* Diphenhydramine 50 mg IV
* Ranitidine 50 mg IV
* Paclitaxel will be administered after the gemcitabine infusion as a 1 hour (IV) infusion
* The initial dose of paclitaxel is 80 mg/m2/weekly for 3 out of 4 weeks (Day 1, 8, 15)
Paclitaxel Dose Levels:
* Dose Level 1 \_\_\_\_\_\_\_\_80 mg/m2/weekly
* Dose Level -1 \_\_\_\_\_
|
|---|---|
|
Progression-Free Survival (PFS)
|
8.5 months
Interval 5.0 to 10.0
|
SECONDARY outcome
Timeframe: Baseline through duration of treatment an average of 1 yearPopulation: Participants with advanced chemotherapy naïve with non-squamous non-small cell lung cancer.
All adverse events will be recorded as to the grade and relationship to the study drug in accordance with the Common Terminology Criteria for Adverse Events (CTCAE v 3.0)
Outcome measures
| Measure |
Paclitaxel and Gemcitabine + Avastin
n=36 Participants
Patients will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks which constitutes one cycle (4 weeks). Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will continue until disease progression, intolerable toxicity, or withdrawal of consent.
Paclitaxel: -Prior to receiving paclitaxel, all patients will receive the following premedications one hour before the infusion:
* Dexamethasone 20mg, intravenously (IV)
* Diphenhydramine 50 mg IV
* Ranitidine 50 mg IV
* Paclitaxel will be administered after the gemcitabine infusion as a 1 hour (IV) infusion
* The initial dose of paclitaxel is 80 mg/m2/weekly for 3 out of 4 weeks (Day 1, 8, 15)
Paclitaxel Dose Levels:
* Dose Level 1 \_\_\_\_\_\_\_\_80 mg/m2/weekly
* Dose Level -1 \_\_\_\_\_
|
|---|---|
|
Number of Participants With Adverse Events
|
36 participants
|
SECONDARY outcome
Timeframe: Baseline up to 84 monthsPopulation: Participants with advanced chemotherapy naïve with non-squamous non-small cell lung cancer.
Overall Survival is defined as the number of days from the day the subject started treatment to the day the subject experiences death or lost to follow up.
Outcome measures
| Measure |
Paclitaxel and Gemcitabine + Avastin
n=36 Participants
Patients will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks which constitutes one cycle (4 weeks). Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will continue until disease progression, intolerable toxicity, or withdrawal of consent.
Paclitaxel: -Prior to receiving paclitaxel, all patients will receive the following premedications one hour before the infusion:
* Dexamethasone 20mg, intravenously (IV)
* Diphenhydramine 50 mg IV
* Ranitidine 50 mg IV
* Paclitaxel will be administered after the gemcitabine infusion as a 1 hour (IV) infusion
* The initial dose of paclitaxel is 80 mg/m2/weekly for 3 out of 4 weeks (Day 1, 8, 15)
Paclitaxel Dose Levels:
* Dose Level 1 \_\_\_\_\_\_\_\_80 mg/m2/weekly
* Dose Level -1 \_\_\_\_\_
|
|---|---|
|
Overall Survival (OS)
|
25.5 months
Interval 15.0 to 35.0
|
SECONDARY outcome
Timeframe: Baseline up to 12 monthsPopulation: Participants with advanced chemotherapy naïve with non-squamous non-small cell lung cancer.
The percentage of patients who achieve a complete response and partial response according to RECIST criteria (v1.0).
Outcome measures
| Measure |
Paclitaxel and Gemcitabine + Avastin
n=36 Participants
Patients will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks which constitutes one cycle (4 weeks). Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will continue until disease progression, intolerable toxicity, or withdrawal of consent.
Paclitaxel: -Prior to receiving paclitaxel, all patients will receive the following premedications one hour before the infusion:
* Dexamethasone 20mg, intravenously (IV)
* Diphenhydramine 50 mg IV
* Ranitidine 50 mg IV
* Paclitaxel will be administered after the gemcitabine infusion as a 1 hour (IV) infusion
* The initial dose of paclitaxel is 80 mg/m2/weekly for 3 out of 4 weeks (Day 1, 8, 15)
Paclitaxel Dose Levels:
* Dose Level 1 \_\_\_\_\_\_\_\_80 mg/m2/weekly
* Dose Level -1 \_\_\_\_\_
|
|---|---|
|
Objective Response Rate
|
22 Participants
|
Adverse Events
Paclitaxel and Gemcitabine + Avastin
Serious events: 25 serious events
Other events: 36 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Paclitaxel and Gemcitabine + Avastin
n=36 participants at risk
Patients will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks which constitutes one cycle (4 weeks). Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will continue until disease progression, intolerable toxicity, or withdrawal of consent.
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia: Induction
|
16.7%
6/36 • Number of events 6 • Baseline up to 24 months
|
|
General disorders
Fatigue: Induction
|
2.8%
1/36 • Number of events 1 • Baseline up to 24 months
|
|
Gastrointestinal disorders
Nausea Vomiting: Induction
|
2.8%
1/36 • Number of events 1 • Baseline up to 24 months
|
|
Cardiac disorders
Hypertension Grade: end of Cycle 1
|
2.8%
1/36 • Number of events 1 • Baseline up to 24 months
|
|
Cardiac disorders
Hypertension: end of induction
|
13.9%
5/36 • Number of events 5 • Baseline up to 24 months
|
|
Cardiac disorders
Hypertension grade: maintenance
|
11.1%
4/36 • Number of events 4 • Baseline up to 24 months
|
|
Renal and urinary disorders
Proteinuria: Induction
|
11.1%
4/36 • Number of events 4 • Baseline up to 24 months
|
|
Renal and urinary disorders
Proteinuria: Maintenance
|
11.1%
4/36 • Number of events 4 • Baseline up to 24 months
|
Other adverse events
| Measure |
Paclitaxel and Gemcitabine + Avastin
n=36 participants at risk
Patients will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks which constitutes one cycle (4 weeks). Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will continue until disease progression, intolerable toxicity, or withdrawal of consent.
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia: Induction
|
38.9%
14/36 • Number of events 14 • Baseline up to 24 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia: Induction
|
47.2%
17/36 • Number of events 17 • Baseline up to 24 months
|
|
Blood and lymphatic system disorders
Anemia: Induction
|
75.0%
27/36 • Number of events 27 • Baseline up to 24 months
|
|
Gastrointestinal disorders
Nausea/Vomiting: Induction
|
47.2%
17/36 • Number of events 17 • Baseline up to 24 months
|
|
Gastrointestinal disorders
Diarrhea: Induction
|
55.6%
20/36 • Number of events 20 • Baseline up to 24 months
|
|
General disorders
Fatigue: Induction
|
88.9%
32/36 • Number of events 32 • Baseline up to 24 months
|
|
Nervous system disorders
Neuropathy: Induction
|
52.8%
19/36 • Number of events 19 • Baseline up to 24 months
|
|
Cardiac disorders
Hypertension grade: end of Cycle 1
|
72.2%
26/36 • Number of events 26 • Baseline up to 24 months
|
|
Cardiac disorders
Hypertension grade: end of induction
|
88.9%
32/36 • Number of events 32 • Baseline up to 24 months
|
|
Cardiac disorders
Hypertension grade: maintenance
|
47.2%
17/36 • Number of events 17 • Baseline up to 24 months
|
|
Renal and urinary disorders
Proteinuria: Induction
|
38.9%
14/36 • Number of events 14 • Baseline up to 24 months
|
|
Cardiac disorders
Proteinuria: Maintenance
|
38.9%
14/36 • Number of events 14 • Baseline up to 24 months
|
Additional Information
Francisco Robert, MD
University of Alabama at Birmingham
Phone: 205-934-5077
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place