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

Sponsor:	Southwest Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00828139

Purpose

RATIONALE: 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.

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.

Condition	Intervention	Phase
Lung Cancer	Biological: aflibercept Drug: topotecan hydrochloride	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized 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:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Topotecan hydrochloride Topotecan Aflibercept

U.S. FDA Resources

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

Primary Outcome Measures:

Progression-free survival at 3 months [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rate (confirmed and unconfirmed, complete and partial responses) [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Frequency and severity of toxicities [ Designated as safety issue: Yes ]

Estimated Enrollment:	172
Study Start Date:	May 2009
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I Patients receive 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 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: aflibercept Given IV Drug: topotecan hydrochloride Given IV
Active Comparator: 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.	Drug: topotecan hydrochloride Given IV

Arms

Assigned Interventions

Experimental: Arm I

Patients receive 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 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: aflibercept

Given IV

Drug: topotecan hydrochloride

Given IV

Active Comparator: 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.

Drug: topotecan hydrochloride

Given IV

Detailed Description:

OBJECTIVES:

Primary

Evaluate the efficacy of topotecan hydrochloride with vs without 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

Assess the response rate (confirmed and unconfirmed, complete and partial responses) in a subset of patients with measurable disease.
Assess the overall survival of these patients.
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 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 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

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 21 days since prior and no concurrent radiotherapy and recovered
At least 28 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)
Concurrent chronic therapeutic doses of low molecular weight heparin allowed

Contacts and Locations

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

Show 191 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Jeffrey W. Allen, MD	University of Tennessee
Investigator:	Shirish M. Gadgeel, MD	Barbara Ann Karmanos Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Laurence H. Baker, Southwest Oncology Group - Group Chair's Office
ClinicalTrials.gov Identifier:	NCT00828139 History of Changes
Other Study ID Numbers:	CDR0000632614, SWOG-S0802
Study First Received:	January 22, 2009
Last Updated:	April 7, 2011
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

extensive stage small cell lung cancer
recurrent small cell lung cancer

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
Topotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012