Clinical trial NCT00655850
Conditions: Non-Small Cell Lung Cancer
Keywords: Lung Cancer Non-Small Cell Lung Cancer Metronomic Chemotherapy
Sponsor: University of Alabama at Birmingham
Start date: 2008-03-01; Completion date: 2016-09-01
Enrollment: 39 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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 NSCLC treated with metronomic chemotherapy plus Avastin. Also, currently there are no defined markers that predict for clinical benefit to Avastin. Preliminary studies show that there are several observations that support the concept of metronomic chemotherapy with or without the combination of an anti-angiogenic agent. The metronomic chemotherapy with Avastin was shown to enhance the clinical endpoints of the study (response rate and progressive-free survival). Proof of metronomic scheduling requires the development of appropriate intermediate surrogate markers. Several markers will be assessed.

Detailed description:
This is a non-randomized, open-label, pilot Phase II study of metronomic chemotherapy plus Avastin in chemo naïve subjects with advanced non-squamous, non-small cell carcinoma of the lung. The primary endpoint of this study is to assess the overall progression-free survival.

Subjects will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks, and Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy will be expressed as a 4-week cycle. Tumor response to treatment will be evaluated every 8 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 then continue until disease progression, intolerable toxicity or withdrawal of consent.

Potential biologic parameters to monitor anti-tumor activity of metronomic chemotherapy will be evaluated in 10 subjects. These biomarkers include: sequential determination of blood levels of VEGF, VEGFR2, thrombospondin-1, E-selectin, ICAM-1, and circulating endothelial cells and endothelial precursor cells.

Arms: arm 1: 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.
Interventions: intervention 1: Paclitaxel intervention 2: Gemcitabine intervention 3: Avastin
Intervention descriptions: intervention 1: * 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 \_\_\_\_\_\_\_\_70 mg/m2/weekly intervention 2: Premedication

* Prophylactic antiemetics: 5-HT3-receptor antagonist prior to infusion with gemcitabine.
* Prior to receiving paclitaxel chemotherapy
* Gemcitabine will be given at the initial dose of 200mg/m2/week (Dose Level 1) for 3 out of 4 weeks (Day 1, 8, 15), as a 30 minute (IV) infusion.
* The dose of gemcitabine can be escalated to 300mg/m2/weekly (Dose Level 2) after the first cycle of treatment if no significant toxicity is experienced.

Gemcitabine Dose Levels:

* Dose Level 2 \_\_\_\_\_\_\_\_300 mg/m2/weekly
* Dose Level 1 \_\_\_\_\_\_\_\_200 mg/m2/weekly
* Dose Level -1 \_\_\_\_\_\_\_\_150 mg/m2/weekly intervention 3: * The dose of Avastin is 10 mg/kg IV every 2 weeks
* It will be administered following the administration of chemotherapy
* The first infusion will be administered over 90 minutes; if well tolerated, the second and subsequent doses will be administered as a 60-minute and 30-minute infusion, respectively.
* It should not be administered or mixed with dextrose solutions.

Protocol documents: