Topotecan With or Without Aflibercept in Treating Patients With Extensive-Stage Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00828139
First received: January 22, 2009
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Extensive Stage Small Cell Lung Cancer
Recurrent Small Cell Lung Cancer
Biological: ziv-aflibercept
Drug: topotecan hydrochloride
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: From the date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Estimated to within at least 15% (95% confidence interval).

  • Individual toxicity proportions as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Estimated to within at least 15% (95% confidence interval).

  • Response rate (confirmed and unconfirmed, complete and partial responses) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Estimated to within at least 17% (95% confidence interval.


Enrollment: 137
Study Start Date: May 2009
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: ziv-aflibercept
Given IV
Other Names:
  • aflibercept
  • vascular endothelial growth factor trap
  • VEGF Trap
  • Zaltrap
Drug: topotecan hydrochloride
Given IV
Other Names:
  • hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • TOPO
Active Comparator: 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.
Drug: topotecan hydrochloride
Given IV
Other Names:
  • hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • TOPO

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • Hemoglobin ≥ 10 g/dL
  • Serum creatinine ≤ 1.5 times upper limit of normal OR creatinine clearance ≥ 60 mL/min
  • Urine protein: creatinine ratio < 1 OR urine protein < 500 mg by 24-hour urine collection
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Willing to provide smoking history
  • No evidence of active infection
  • No active bleeding
  • No significant history of bleeding diathesis, including hemoptysis (½ teaspoon of hemoptysis within the past 3 months), or underlying coagulopathy
  • No history of recent arterial embolic events, including any of the following:

    • Myocardial infarction
    • Cerebrovascular accident
    • Transient ischemic attack
    • Worsening of pre-existing angina within the past 6 months
  • No uncontrolled hypertension (systolic BP > 150 mm Hg or diastolic BP > 100 mm Hg)

    • History of hypertension allowed provided it is controlled on anti-hypertensive medications
  • No history of congestive heart failure
  • No history of encephalitis or encephalopathy of any cause
  • No diverticulitis, gastrointestinal bleeding, or peptic ulcer within the past 3 months
  • No known AIDS or HIV-1 associated complex
  • No known history of immune or immunodeficiency disorders
  • No unstable or pre-existing major medical conditions except for cancer-related abnormalities
  • No other prior malignancy except for any of the following:

    • Adequately treated basal cell or squamous cell skin cancer
    • In situ cervical cancer
    • Adequately treated stage I or II cancer currently in complete remission
    • Any other cancer from which the patient been disease-free for 5 years
  • Concurrent chronic therapeutic doses of low molecular weight heparin allowed
  • At least 21 days since prior and no concurrent radiotherapy and recovered
  • At least 28 days since prior and no concurrent surgery (e.g., thoracic or other major surgeries) and recovered
  • No prior bevacizumab or other anti-angiogenic therapies including, but not limited to, small molecule tyrosine kinase inhibitors
  • No concurrent enzyme-inducing anticonvulsant drugs

    • Non-enzyme-inducing anticonvulsant drugs (e.g., Keppra) allowed
  • Concurrent chronic oral anticoagulation therapy allowed provided INR is maintained in the therapeutic range (INR 2-3)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00828139

  Show 257 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Jeffrey Allen Southwest Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00828139     History of Changes
Other Study ID Numbers: NCI-2009-01182, NCI-2009-01182, SWOG-S0802, CDR0000632614, S0802, S0802
Study First Received: January 22, 2009
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Endothelial Growth Factors
Topotecan
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014