A Randomized Phase II Trial of Weekly Topotecan With and Without AVE0005 (Aflibercept; NSC-724770) in Patients With Platinum Treated Extensive Stage Small Cell Lung Cancer (E-SCLC)
Overview
- Phase
- Phase 2
- Intervention
- ziv-aflibercept
- Conditions
- Extensive Stage Small Cell Lung Cancer
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 189
- Locations
- 257
- Primary Endpoint
- Progression-free Survival (PFS)
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed extensive stage small cell lung cancer
- •Progressive or recurrent disease following one (and only one) standard first-line platinum-containing regimen (cisplatin or carboplatin)
- •Measurable or non-measurable disease per RECIST criteria
- •Disease must be outside a previously irradiated field OR a new lesion must be inside the irradiated field
- •Disease must be outside a previously resected area OR a new lesion must be present
- •No known brain metastasis unless the metastasis has been treated and is stable for ≥ 3 months prior to study entry
- •No leptomeningeal involvement or brain stem metastasis
- •Zubrod performance status 0-1
- •ANC ≥ 1,500/mm\^3
- •Platelet count ≥ 100,000/mm\^3
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I (ziv-aflibercept, topotecan hydrochloride)
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.
Intervention: ziv-aflibercept
Arm I (ziv-aflibercept, topotecan hydrochloride)
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.
Intervention: topotecan hydrochloride
Arm II (topotecan hydrochloride)
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.
Intervention: topotecan hydrochloride
Outcomes
Primary Outcomes
Progression-free Survival (PFS)
Time Frame: Disease assessments were performed every 6 weeks, up to 2 years.
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.
Secondary Outcomes
- Response Rate (Confirmed and Unconfirmed, Complete and Partial Responses)(Disease assessment for response were performed every 6 weeks, up to 2 years.)
- Overall Survival(Weekly, up to 2 years.)
- Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drugs(Toxicity assessment was evaluated after each cycle (21 days), up to 2 years.)