This randomized phase II trial is studying topotecan to see how well it works when given with or without aflibercept in treating patients with extensive-stage small cell lung cancer. Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Combinations of biological substances in aflibercept may be able to carry tumor-killing substances directly to small cell lung cancer cells. Aflibercept may also stop the growth of small cell lung cancer by blocking blood flow to the tumor. It is not yet known whether topotecan is more effective with or without aflibercept in treating patients with small cell lung cancer.
PRIMARY OBJECTIVES: I. Evaluate the efficacy of topotecan hydrochloride with vs without aflibercept (ziv-aflibercept), in terms of progression-free survival at 3 months, in patients with extensive stage small cell lung cancer previously treated with platinum-based therapy. SECONDARY OBEJCTIVES: I. Assess the response rate (confirmed and unconfirmed, complete and partial responses) in a subset of patients with measurable disease. II. Assess the overall survival of these patients. III. Evaluate the frequency and severity of toxicities of these regimens in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to response to prior platinum-based therapy (platinum-sensitive disease vs platinum-refractory disease). Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive ziv-aflibercept IV over 1 hour on day 1 and topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive or stable disease after 4 courses may then receive ziv-aflibercept IV on day 1 and topotecan hydrochloride IV on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive or stable disease after 4 courses may then receive topotecan hydrochloride IV on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
189
Given IV
Given IV
Northeast Alabama Regional Medical Center
Anniston, Alabama, United States
Providence Hospital
Mobile, Alabama, United States
Arizona Cancer Center at UMC Orange Grove
Tucson, Arizona, United States
Arizona Cancer Center at University Medical Center North
Tucson, Arizona, United States
University of Arizona Health Sciences Center
Tucson, Arizona, United States
Progression-free Survival (PFS)
From the date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Progression is defined as 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration.
Time frame: Disease assessments were performed every 6 weeks, up to 2 years.
Overall Survival
Estimated to within at least 15% (95% confidence interval).
Time frame: Weekly, up to 2 years.
Response Rate (Confirmed and Unconfirmed, Complete and Partial Responses)
The number of confirmed and unconfirmed complete and partial responses in the subset of patients with measurable disease per RECIST 1.0. Estimated to within at least 17% (95% confidence interval). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Disease assessment for response were performed every 6 weeks, up to 2 years.
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drugs
Adverse Events (AEs) are reported by CTCAE Version 3.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. The events listed here are not necessary to be included in Serious Adverse Event. A serious event could be death, life-threatening, hospitalization, disability or permanent damage, congenital anomaly...Grade 3 through 5 adverse event may not meet the criterion of serious adverse event.
Time frame: Toxicity assessment was evaluated after each cycle (21 days), up to 2 years.
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