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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00079040
First received: March 8, 2004
Last updated: February 26, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Biological: bevacizumab
Drug: cisplatin
Drug: etoposide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Cisplatin Plus Etoposide (PE) Plus Bevacizumab (NSC #704865) for Previously Untreated Extensive Stage Small Cell Lung Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Percentage of Participants Alive and Progression-free (PF) at 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 1 year ] [ Designated as safety issue: No ]
    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 [ Time Frame: Assessed every 6 weeks ] [ Designated as safety issue: No ]
    Number of patients with complete or partial response by RECIST criteria.


Enrollment: 65
Study Start Date: June 2004
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cisplatin, Etoposide & Bevacizumab Biological: bevacizumab
15 mg/kg IV infusion over 90 minutes day 1 of a 21-day cycle
Other Name: Avastin
Drug: cisplatin
60 mg/m2 IV over 30-60 minutes day 1 of a 21-day cycle
Drug: etoposide
120 mg/m2 IV over 60 minutes days 1, 2, and 3 of a 21-day cycle

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the 6-month progression-free survival of patients with previously untreated extensive stage small cell lung cancer treated with cisplatin, etoposide, and bevacizumab.

II. Determine the 6-month survival and response rate in patients treated with this regimen.

III. Determine the toxicity of this regimen in these patients.

SECONDARY OBJECTIVES:

I. Correlate pretreatment plasma levels of vascular endothelial growth factor (VEGF) with response and progression-free and overall survival of patients treated with this regimen.

II. Correlate elevated plasma levels of endothelial cell-specific proteins (VCAM, E-selectin) with response in patients treated with this regimen.

III. Correlate pre- and post-treatment plasma levels of basic fibroblast growth factor with response and progression-free and overall survival of patients treated with this regimen.

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.

  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 small cell lung cancer, staged as extensive disease
  • Measurable disease per RECIST criteria
  • Previously irradiated lesions must not be the sole site of measurable disease
  • Age 18 and over
  • ECOG Performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • No history of hemorrhagic disorders
  • Bilirubin ≤ 1.5 mg/dL
  • PTT ≤ upper limit of normal
  • INR ≤ 1.5
  • Creatinine ≤ 1.5 mg/dL
  • Proteinuria < 1+. For proteinuria ≥ 1+, urine protein must be ≤ 1 g/24 hours
  • Hypertension must be well-controlled (≤ 150/85) on a stable regimen of antihypertensive therapy
  • Not pregnant or nursing - patient must have negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study treatment

Exclusion Criteria

  • Prior radiotherapy to the site of evaluable disease
  • CNS metastases by CT scan or MRI within the past 4 weeks
  • Symptomatic congestive heart failure
  • Cardiac arrhythmia
  • History of thrombotic disorders
  • Clinically significant peripheral artery disease
  • Arterial thromboembolic event within the past 6 months, including transient ischemic attack, cerebrovascular accident, unstable angina, or myocardial infarction
  • History of gross hemoptysis (i.e., ≥ 1 teaspoon of bright red blood)
  • Other malignancy within the past 5 years except cured basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • Ongoing or active infection
  • Psychiatric illness or social situation that would preclude study compliance
  • Serious nonhealing wound, ulcer, or bone fracture
  • Prior immunotherapy for lung cancer
  • Prior biologic therapy for lung cancer
  • Prior chemotherapy for lung cancer
  • Concurrent local radiotherapy for pain control or life-threatening situations
  • Prior major surgery within 28 days
  • Prior minor surgery or needle biopsies within 7 days
  • Concurrent chronic daily aspirin (> 325 mg/day)
  • Concurrent nonsteroidal anti-inflammatory agents known to inhibit platelet function
  • Concurrent therapeutic anticoagulation, but prophylactic anticoagulation of venous access devices is allowed
  • Concurrent treatment with Dipyridamole, Ticlopidine, Clopidogrel, Cilostazol
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00079040

  Show 60 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Alan B. Sandler, MD Vanderbilt-Ingram Cancer Center
  More Information

Additional Information:
Publications:
Sandler A, Szwarc S, Dowlati A, et al.: A phase II study of cisplatin (P) plus etoposide (E) plus bevacizumab (B) for previously untreated extensive stage small cell lung cancer (SCLC) (E3501): a trial of the Eastern Cooperative Oncology Group. [Abstract] J Clin Oncol 25 (Suppl 18): A-7564, 400s, 2007.

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00079040     History of Changes
Other Study ID Numbers: NCI-2012-02944, ECOG-E3501, CDR0000353484
Study First Received: March 8, 2004
Results First Received: November 19, 2009
Last Updated: February 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
extensive stage 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
Etoposide phosphate
Bevacizumab
Cisplatin
Etoposide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014