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Cisplatin, Etoposide, and Bevacizumab in Treating Patients With Previously Untreated Extensive Stage Small Cell Lung Cancer

Primary Purpose

Extensive Stage Small Cell Lung Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cisplatin
etoposide
bevacizumab
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Extensive Stage Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Histologic (or cytologic) proof of small cell lung cancer must be confirmed Patients must be clinically staged as extensive disease Patients must have measurable disease as defined by RECIST criteria; baseline scans/evaluation used to document measurable disease must be done within 4 weeks prior to registration; patients with measurable disease only or with both measurable and non-measurable disease are eligible Patients must have ECOG performance status of 0, 1, or 2 Patients may not have had prior chemotherapy, immunotherapy, or biological therapy for lung cancer; previously irradiated lesions must not be the only site of measurable disease ANC > 1500/mm^3 Platelets >= 100,000/mm^3 Creatinine =< 1.5 mg Total bilirubin =< 1.5 mg Pregnant or breastfeeding women are excluded from the study because the agents used in this study may be teratogenic to a fetus or child and there is no information on the excretion of the agents or their metabolites into breast milk; all females of childbearing potential must have a blood test or urine study within 2 weeks, prior to registration to rule out pregnancy Women of childbearing potential and sexually active males are strongly advised to use an effective method of contraception Patients must be disease-free for > 5 years if they have a history of prior malignancies (except for cured basal or squamous cell skin cancers, or carcinoma in situ of the cervix) Patients must be considered on psychosocial grounds to be willing and able to comply with the requirements of treatment and follow-up Patients must not have CNS metastases; a head CT is required within 4 weeks prior to study entry for evaluation (MRIs are also acceptable) Urine dipstick for proteinuria of less than 1+ is required within 7 days prior to study entry; if urine dipstick is >= 1+ then a 24 hour urine for protein must demonstrate =< 1 gm of protein in 24 hours to allow participation in the study; NOTE: Urinalysis is also acceptable Patients must have INR =< 1.5 and a PTT no greater than the institutional upper limit of normal within 1 week prior to registration Patients must not have ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Patients must not have history of thrombotic or hemorrhagic disorders; patients must not have recently (within 6 months of registration) experienced arterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, or myocardial infarction (MI); patients must also not have clinically significant peripheral artery disease Patients with history of hypertension must be well-controlled (=< 150/85) on a stable regimen of anti-hypertensive therapy Patients must not be receiving chronic daily treatment with aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory agents known to inhibit platelet function; treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal) is also not allowed Patients must not have serious non-healing wound, ulcer, or bone fracture, or major surgical procedure within 28 days prior to starting treatment; patients must not have had minor surgery or needle biopsies within 7 days of treatment Patients must not be on therapeutic anticoagulation Patients with a history of gross hemoptysis (defined as bright red blood of a 1/2 teaspoon or more) will be excluded from this trial Patients must have had no prior radiation therapy to the site of evaluable disease

Sites / Locations

  • Eastern Cooperative Oncology Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (cisplatin, etoposide, bevacizumab)

Arm Description

Chemotherapy: Patients receive cisplatin IV over 30-60 minutes on day 1 and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab therapy: Beginning concurrently with chemotherapy, patients receive bevacizumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 17 courses (1 year) in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Percentage of Participants Alive and Progression-free (PF) at 6 Months
Progression-free survival was defined to be the interval in months from the date of registration to the date of documented disease progression or to death without progression. Patients alive without progression at 6 months were included in the numerator when calculating the progression-free rate.

Secondary Outcome Measures

Overall Survival
Overall survival is defined as the time from registration to death or date last known alive. Patients alive at last follow-up are censored.
Best Objective Response
Number of patients with complete or partial response by RECIST criteria.

Full Information

First Posted
March 8, 2004
Last Updated
April 28, 2014
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00079040
Brief Title
Cisplatin, Etoposide, and Bevacizumab in Treating Patients With Previously Untreated Extensive Stage Small Cell Lung Cancer
Official Title
A Phase II Study of Cisplatin Plus Etoposide (PE) Plus Bevacizumab (NSC #704865) for Previously Untreated Extensive Stage Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
January 2006 (undefined)
Primary Completion Date
January 2009 (Actual)
Study Completion Date
January 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase II trial is studying how well giving cisplatin and etoposide together with bevacizumab works in treating patients with previously untreated extensive-stage small cell lung cancer. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or deliver tumor-killing substances to them. Giving chemotherapy with a monoclonal antibody may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the combination of PE plus concurrent and sequential bevacizumab with respect to six month progression free survival in patients with previously untreated SCLC. II. To evaluate the combination of PE plus concurrent and sequential bevacizumab with respect to survival and response rate. III. To evaluate toxicity in patients with extensive small cell lung cancer, treated with the combination of PE plus concurrent and sequential bevacizumab who have received no prior systemic chemotherapy. SECONDARY OBJECTIVES: I. To determine if pre-treatment levels of plasma VEGF predict response to chemotherapy with Etoposide-Cisplatin plus concurrent + sequential bevacizumab. II. To determine if pre-treatment plasma VEGF is predictive of progression free survival and overall survival in advanced SCLC. III. To determine whether elevated plasma levels of endothelial cell-specific proteins (VCAM, E-selectin), reflective of chemotherapy or bevacizumab induced endothelial damage, are useful markers in assessing response to Etoposide/Cisplatin plus concurrent + sequential bevacizumab. IV. To determine whether pre- and post-treatment plasma levels of basic fibroblast growth factor (bFGF) is predictive of progression free survival and overall survival or predictive of response to therapy. OUTLINE: This is a multicenter study. Chemotherapy: Patients receive cisplatin IV over 30-60 minutes on day 1 and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab therapy: Beginning concurrently with chemotherapy, patients receive bevacizumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 17 courses (1 year) in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 weeks for up to 3 years from study entry.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Extensive Stage Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
65 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (cisplatin, etoposide, bevacizumab)
Arm Type
Experimental
Arm Description
Chemotherapy: Patients receive cisplatin IV over 30-60 minutes on day 1 and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab therapy: Beginning concurrently with chemotherapy, patients receive bevacizumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 17 courses (1 year) in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
cisplatin
Other Intervention Name(s)
CACP, CDDP, CPDD, DDP
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
EPEG, VP-16, VP-16-213
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Other Intervention Name(s)
anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Percentage of Participants Alive and Progression-free (PF) at 6 Months
Description
Progression-free survival was defined to be the interval in months from the date of registration to the date of documented disease progression or to death without progression. Patients alive without progression at 6 months were included in the numerator when calculating the progression-free rate.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Overall survival is defined as the time from registration to death or date last known alive. Patients alive at last follow-up are censored.
Time Frame
Assessed every 3 months for 2 years, then every 6 months for 1 year
Title
Best Objective Response
Description
Number of patients with complete or partial response by RECIST criteria.
Time Frame
Assessed every 6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologic (or cytologic) proof of small cell lung cancer must be confirmed Patients must be clinically staged as extensive disease Patients must have measurable disease as defined by RECIST criteria; baseline scans/evaluation used to document measurable disease must be done within 4 weeks prior to registration; patients with measurable disease only or with both measurable and non-measurable disease are eligible Patients must have ECOG performance status of 0, 1, or 2 Patients may not have had prior chemotherapy, immunotherapy, or biological therapy for lung cancer; previously irradiated lesions must not be the only site of measurable disease ANC > 1500/mm^3 Platelets >= 100,000/mm^3 Creatinine =< 1.5 mg Total bilirubin =< 1.5 mg Pregnant or breastfeeding women are excluded from the study because the agents used in this study may be teratogenic to a fetus or child and there is no information on the excretion of the agents or their metabolites into breast milk; all females of childbearing potential must have a blood test or urine study within 2 weeks, prior to registration to rule out pregnancy Women of childbearing potential and sexually active males are strongly advised to use an effective method of contraception Patients must be disease-free for > 5 years if they have a history of prior malignancies (except for cured basal or squamous cell skin cancers, or carcinoma in situ of the cervix) Patients must be considered on psychosocial grounds to be willing and able to comply with the requirements of treatment and follow-up Patients must not have CNS metastases; a head CT is required within 4 weeks prior to study entry for evaluation (MRIs are also acceptable) Urine dipstick for proteinuria of less than 1+ is required within 7 days prior to study entry; if urine dipstick is >= 1+ then a 24 hour urine for protein must demonstrate =< 1 gm of protein in 24 hours to allow participation in the study; NOTE: Urinalysis is also acceptable Patients must have INR =< 1.5 and a PTT no greater than the institutional upper limit of normal within 1 week prior to registration Patients must not have ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Patients must not have history of thrombotic or hemorrhagic disorders; patients must not have recently (within 6 months of registration) experienced arterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, or myocardial infarction (MI); patients must also not have clinically significant peripheral artery disease Patients with history of hypertension must be well-controlled (=< 150/85) on a stable regimen of anti-hypertensive therapy Patients must not be receiving chronic daily treatment with aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory agents known to inhibit platelet function; treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal) is also not allowed Patients must not have serious non-healing wound, ulcer, or bone fracture, or major surgical procedure within 28 days prior to starting treatment; patients must not have had minor surgery or needle biopsies within 7 days of treatment Patients must not be on therapeutic anticoagulation Patients with a history of gross hemoptysis (defined as bright red blood of a 1/2 teaspoon or more) will be excluded from this trial Patients must have had no prior radiation therapy to the site of evaluable disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alan Sandler
Organizational Affiliation
Eastern Cooperative Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Eastern Cooperative Oncology Group
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Cisplatin, Etoposide, and Bevacizumab in Treating Patients With Previously Untreated Extensive Stage Small Cell Lung Cancer

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