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

Extensive Stage Small Cell Lung Cancer Clinical Trial

Official title:

A Phase II Study of Cisplatin Plus Etoposide (PE) Plus Bevacizumab (NSC #704865) for Previously Untreated Extensive Stage Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00079040
• Other study ID #: NCI-2012-02944
• Secondary ID: NCI-2012-02944EC
• Status: Completed
• Phase: Phase 2
• First received: March 8, 2004
• Last updated: April 28, 2014
• Start date: January 2006
• Est. completion date: January 2009

Study information

• Verified date: December 2012
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Extensive Stage Small Cell Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Drug:
• cisplatin
Given IV
• etoposide
Given IV

Biological:
• bevacizumab
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Eastern Cooperative Oncology Group	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6 months	No
Secondary	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.	Assessed every 3 months for 2 years, then every 6 months for 1 year	No
Secondary	Best Objective Response	Number of patients with complete or partial response by RECIST criteria.	Assessed every 6 weeks	No