A Study of Paclitaxel Plus Bevacizumab in Patients With Chemosensitive Relapsed Small Cell Lung Cancer

Sponsor

Hoosier Cancer Research Network (Other)

Overall Status

Completed

CT.gov ID

NCT00317200

Collaborator

Genentech, Inc. (Industry), Walther Cancer Institute (Other)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Improvements in therapy for relapsed SCLC are much needed. Paclitaxel has been previously tested and found to have significant single agent activity in relapsed SCLC, including in refractory patients. Angiogenesis plays an important role in SCLC, increased VEGF levels are associated with worse outcomes. Bevacizumab, a monoclonal antibody to VEGF, increase response rates and survival when combined with chemotherapy agents compared with the chemotherapy agent alone in NSCLC, breast cancer, and colorectal cancer. Paclitaxel plus bevacizumab, in the dose and schedule proposed in this study, improves response rates and progression free survival compared with paclitaxel alone in women with metastatic breast cancer. Therefore, we will be testing the safety, feasibility, and efficacy of this regimen in patients with chemosensitive relapsed SCLC.

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Cancer	Drug: Paclitaxel Drug: Bevacizumab	Phase 2

Detailed Description

OUTLINE: This is a multi-center study.

Paclitaxel 90 mg/m2 IV infusion over 1 hour days 1, 8 and 15 of 28 day cycle

Plus

Bevacizumab 10 mg/kg on days 1 and 15 of 28 day cycle.

1 cycle = 28 days (4 weeks)
Disease assessments will be performed per RECIST every other cycle
After a minimum of 4 cycles or a maximum of 6 cycles of combination chemotherapy, bevacizumab monotherapy may continue until disease progression or intolerable side effects

ECOG Performance Status 0 or 1

Hematopoietic:

White blood cell count > 3,000 mm3
Absolute neutrophil count (ANC) > 1,500 mm3
Platelet count > 100,000 mm3
International normalized ration (INR) of prothrombin time ≤ 1.2
PTT no more than 5 seconds longer than the ULN

Hepatic:

Bilirubin < 1.5 x ULN
Aspartate aminotransferase (AST, SGOT) < 2.5 x ULN

Renal:

Urine protein:creatinine ratio <1.0

Cardiovascular:

No history of myocardial infarction or angina pectoris/anginal equivalent in the last 6 months. Note: The patient may be on anti-anginal medications if the symptoms have been entirely controlled for greater than 6 months.
No history of uncontrolled congestive heart failure or uncontrolled hypertension

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Paclitaxel Plus Bevacizumab in Patients With Chemosensitive Relapsed Small Cell Lung Cancer (SCLC): A Safety, Feasibility and Efficacy Study

Study Start Date :

Apr 1, 2006

Actual Primary Completion Date :

Nov 1, 2007

Actual Study Completion Date :

Nov 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Paclitaxel + Devacizumab in patients with chemosensitive relapsed small cell lung cancer.	Drug: Paclitaxel Paclitaxel 90 mg/m2 IV infusion over 1 hour, days 1, 8 and 15 of 28 day cycle. Drug: Bevacizumab Bevacizumab 10 mg/kg, days 1 and 15 of 28 day cycle

Arm

Intervention/Treatment

Active Comparator: 1

Paclitaxel + Devacizumab in patients with chemosensitive relapsed small cell lung cancer.

Drug: Paclitaxel

Paclitaxel 90 mg/m2 IV infusion over 1 hour, days 1, 8 and 15 of 28 day cycle.

Drug: Bevacizumab

Bevacizumab 10 mg/kg, days 1 and 15 of 28 day cycle

Outcome Measures

Primary Outcome Measures

To determine progression free survival(PFS) of this regimen in patients with chemosensitive relapsed small cell lung cancer (SCLC). [18 months]

Secondary Outcome Measures

To determine the response rate of the combination of paclitaxel and bevacizumab with chemosensitive SCLC. [18 months]
To determine the toxicity of the combination of paclitaxel and bevacizumab in patients with SCLC. [18 months]
To determine overall survival. [18 months]
To assess VEGF polymorphisms in the study population. [18 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologic or cytologic proof of small cell lung cancer
Chemo-sensitive disease defined as relapsed after 60 days from completion of first line chemotherapy.
Measurable disease according to RECIST and obtained by imaging within 28 days prior to being registered for protocol therapy.
Must have received treatment with at least 1 but not more than 2 prior chemotherapy regimens. (At least one regimen must contain a platinum agent. Previous treatment with irinotecan is allowed.)
Prior radiation therapy must be completed at least 21 days prior to being registered for protocol therapy, and toxicities due to radiation must have recovered to ≤ grade 1 or baseline prior to registration.
Prior cancer treatment must be completed at least 21 days prior to being registered for protocol therapy and the subject must have recovered from the acute toxicity effects of the regimen prior to registration.

Exclusion Criteria:

No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.
No history or radiographic evidence of CNS involvement by head CT or MRI within 42 days prior to registration.
No history of seizures, transient ischemic attack or stroke.
No clinically significant infections as judged by the treating investigator.
No other active cancer except SCLC.
No prior treatment with topoisomerase I inhibitor.
No contraindications to the use of paclitaxel or bevacizumab as per the investigator's clinical judgment.
Must not have grade 3 or greater peripheral neuropathy.
Must not have had major surgical procedure, open biopsy, or significant traumatic injury within 28 days of being registered for protocol therapy.
No anticipation of need for major surgical procedure during the course of the study.
Patients may not have had a minor surgical procedure, placement of an access device or fine needle aspiration within 7 days prior to being registered for protocol therapy.
No evidence of bleeding diathesis or coagulopathy.
No history of deep vein thrombosis or pulmonary embolism.
No full dose/therapeutic anticoagulation with either low molecular weight heparin or unfractionated heparin or coumadin within 10 days prior to registration.
Patients must not have been using aspirin (>325 mg/day) or another nonsteroidal anti-inflammatory medications known to inhibit platelet function on a daily basis within 10 days prior to registration on study.
Patients must not be using any of the following drugs known to inhibit platelet function within 10 days prior to registration: dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and cilostazol (Pletal).
Patients must not have a current non-healing wound or fracture.
Patients must not have a history of or current hemoptysis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Springdale	Arkansas	United States	72764
2	Medical & Surgical Specialists, LLC	Galesburg	Illinois	United States	61401
3	Cancer Care Center of Southern Indiana	Bloomington	Indiana	United States	47403
4	Oncology Hematology Associates of SW Indiana	Evansville	Indiana	United States	47714
5	Fort Wayne Oncology & Hematology, Inc	Fort Wayne	Indiana	United States	46815
6	Center for Cancer Care at Goshen Health System	Goshen	Indiana	United States	46527
7	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202
8	Quality Cancer Center (MCGOP)	Indianapolis	Indiana	United States	46202
9	Community Regional Cancer Center	Indianapolis	Indiana	United States	46256
10	Arnett Cancer Care	Lafayette	Indiana	United States	47904
11	Medical Consultants, P.C.	Muncie	Indiana	United States	47303
12	Center for Cancer Care, Inc., P.C.	New Albany	Indiana	United States	47150
13	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46601
14	Siteman Cancer Center	St. Louis	Missouri	United States	63110
15	Methodist Cancer Center	Omaha	Nebraska	United States	68114
16	Pennsylvania Oncology-Hematology Associates	Philadelphia	Pennsylvania	United States	19106
17	Fox Chase Cancer Center Extramural Research Program	Rockledge	Pennsylvania	United States	19046