S0819: Carboplatin/Paclitaxel With or Without Bevacizumab and/or Cetuximab in Stage IV or Recurrent Non-Small Cell Lung Cancer

This study has suspended participant recruitment.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00946712
First received: July 24, 2009
Last updated: October 7, 2014
Last verified: October 2014

July 24, 2009
October 7, 2014
July 2009
December 2017   (final data collection date for primary outcome measure)
  • Overall survival (OS) [ Time Frame: From date of registration to 3 years or death, whichever comes first ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) of EGFR FISH-positive patients by institutional review [ Time Frame: From date of registration to 3 years or death, whichever comes first ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Designated as safety issue: No ]
  • Progression-free survival (PFS) of EGFR FISH-positive patients by institutional review [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00946712 on ClinicalTrials.gov Archive Site
  • OS and PFS of EGFR FISH-positive patients by centralized review [ Time Frame: From date of registration to 3 years or death, whichever comes first ] [ Designated as safety issue: No ]
  • PFS of the entire study population by centralized review and by institutional review [ Time Frame: From date of registration to 3 years or death, whichever comes first ] [ Designated as safety issue: No ]
  • Response [ Time Frame: From date of registration to 3 years or death, whichever comes first ] [ Designated as safety issue: No ]
  • Toxicity as assessed by NCI CTCAE version 4.0 [ Time Frame: From date of registration to 3 years or death, whichever comes first ] [ Designated as safety issue: Yes ]
  • Comparison of other purported EGFR-related biomarkers with EGFR IHC, EGFR FISH, and patient outcomes [ Time Frame: From date of registration to 3 years or death, whichever comes first ] [ Designated as safety issue: No ]
  • Correlation of KRAS mutations with response and outcome [ Time Frame: From date of registration to 3 years or death, whichever comes first ] [ Designated as safety issue: No ]
  • OS and PFS of EGFR FISH-positive patients by centralized review [ Designated as safety issue: No ]
  • PFS of the entire study population by centralized review and by institutional review [ Designated as safety issue: No ]
  • Response [ Designated as safety issue: No ]
  • Toxicity as assessed by NCI CTCAE version 3.0 [ Designated as safety issue: Yes ]
  • Comparison of other purported EGFR-related biomarkers with EGFR IHC, EGFR FISH, and patient outcomes [ Designated as safety issue: No ]
  • Correlation of KRAS mutations with response and outcome [ Designated as safety issue: No ]
Not Provided
Not Provided
 
S0819: Carboplatin/Paclitaxel With or Without Bevacizumab and/or Cetuximab in Stage IV or Recurrent Non-Small Cell Lung Cancer
A Randomized, Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizumab With or Without Concurrent Cetuximab in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab and cetuximab, 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 carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether giving carboplatin and paclitaxel are more effective with or without bevacizumab and/or cetuximab in treating patients with non-small cell lung cancer (NSCLC).

PURPOSE: This randomized phase III trial is studying carboplatin and paclitaxel to compare how well they work with or without bevacizumab and/or cetuximab in treating patients with stage IV or recurrent non-small cell lung cancer.

OBJECTIVES:

Primary

  • To compare overall survival (OS) in patients with stage IV or recurrent non-small cell lung cancer (NSCLC) treated with carboplatin, paclitaxel, and bevacizumab (if appropriate) with vs without cetuximab.
  • To compare progression-free survival (PFS) of EGFR FISH-positive patients by institutional review.

Secondary

  • To compare OS and PFS of EGFR FISH-positive patients by centralized review.
  • To compare PFS of the entire study population by centralized image review and by institutional review.
  • To compare the response rate (confirmed plus unconfirmed, complete and partial responses) in a subset of patients with measurable disease treated with these regimens.
  • To assess the toxicities of these regimens.
  • To prospectively test EGFR FISH as a predictive marker for the selection of patients for treatment with cetuximab and chemotherapy.
  • To evaluate the role of KRAS mutations in terms of cetuximab efficacy.
  • To compare the results of EGFR FISH with KRAS mutations, EGFR mutations, EGFR IHC, and other purported EGFR-related biomarkers.

Tertiary

  • To compare PFS in patients with advanced NSCLC with an IHC score > 200 treated with carboplatin, paclitaxel, and bevacizumab (if appropriate) with or without cetuximab.
  • To compare OS in patients with advanced NSCLC with an IHC score > 200 treated with carboplatin, paclitaxel, and bevacizumab (if appropriate) with or without cetuximab.

OUTLINE: This is a multicenter study. Patients are stratified according to bevacizumab-appropriate status (yes vs no), smoking status (current or former [no smoking ≥ 1year] vs never [< 100 cigarettes lifetime]), and stage (M1a vs M1b). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive carboplatin and paclitaxel with or without bevacizumab as in arm I. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients may continue to receive cetuximab with or without bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Plasma and tissue samples are collected periodically for further laboratory analysis.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Lung Cancer
  • Biological: bevacizumab
    Given IV
  • Biological: cetuximab
    Given IV
  • Drug: carboplatin
    Given IV
  • Drug: paclitaxel
    Given IV
  • Active Comparator: Arm I
    Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Biological: bevacizumab
    • Drug: carboplatin
    • Drug: paclitaxel
  • Experimental: Arm II
    Patients receive carboplatin and paclitaxel with or without bevacizumab as in arm I. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients may continue to receive cetuximab with or without bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Biological: bevacizumab
    • Biological: cetuximab
    • Drug: carboplatin
    • Drug: paclitaxel
Redman MW, Crowley JJ, Herbst RS, Hirsch FR, Gandara DR. Design of a phase III clinical trial with prospective biomarker validation: SWOG S0819. Clin Cancer Res. 2012 Aug 1;18(15):4004-12. doi: 10.1158/1078-0432.CCR-12-0167. Epub 2012 May 16.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Suspended
1546
Not Provided
December 2017   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), including any of the following subtypes:

    • Adenocarcinoma
    • Large cell carcinoma
    • Squamous cell carcinoma
    • Unspecified
  • Newly diagnosed stage IV disease OR recurrent disease after prior surgery and/or irradiation

    • Patients with additional lesions in an ipsilateral non-primary lobe without M1a or M1b disease are not considered to have stage IV disease and are not eligible
  • Measurable or non-measurable disease documented by CT scan or MRI

    • Pleural effusions, ascites, and laboratory parameters are not acceptable as the only evidence of disease
    • Measurable disease must be outside a previously irradiated field or must have progressed
  • Patients must not have received prior chemotherapy for any stage NSCLC
  • Brain metastases allowed provided they have been controlled for ≥ 2 weeks after completion of treatment and there is no residual neurological dysfunction while off corticosteroids for at least 1 day

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Serum creatinine normal
  • Creatinine clearance ≥ 50 mL/min
  • Urine protein:creatinine ratio ≤ 0.5 OR 24-hour urine protein < 1,000 mg (for patients who will be receiving bevacizumab)
  • Serum bilirubin ≤ 2 times upper limit of normal (ULN) (≤ 5 times ULN for patients with liver metastases)
  • SGOT OR SGPT ≤ 2 times ULN (≤ 5 times ULN for patients with liver metastases)
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 3-6 months after completion of study treatment
  • Agrees to submission of specimens that is sufficient for EGFR FISH testing and other translational medicine studies
  • Willing to provide prior smoking history
  • No significant traumatic injury within the past 28 days
  • No symptomatic sensory neuropathy ≥ grade 2 as assessed by NCI CTCAE v3.0
  • No documented presence of human anti-mouse antibodies
  • No documented evidence of acute hepatitis
  • No active or uncontrolled infection
  • None of the following within the past 6 months:

    • Cerebrovascular accident, myocardial infarction, or unstable angina
    • Uncontrolled hypertension
    • NYHA class II-IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Clinically significant peripheral vascular disease
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (e.g., trastuzumab [Herceptin®] or epoetin alpha)
  • 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 from which the patient is currently in complete remission
    • Any other cancer from which the patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Prior radiotherapy allowed provided patients have recovered from all associated toxicities at the time of study registration
  • No prior cetuximab, gefitinib, erlotinib, or other investigational agents that target the EGFR pathway
  • Patients must not have received prior platinum-based chemotherapy for any purpose
  • No prior bevacizumab or VEGF-related agents
  • No prior chimerized or murine monoclonal antibody therapy
  • At least 28 days since prior surgery (thoracic or other major surgeries) or open biopsy and recovered (for patients who are bevacizumab-appropriate AND bevacizumab is planned)
  • More than 7 days since prior core biopsy
  • No concurrent major surgical procedures
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00946712
CDR0000649817, S0819, U10CA032102
Yes
Southwest Oncology Group
Southwest Oncology Group
National Cancer Institute (NCI)
Study Chair: Roy S. Herbst, MD, PhD M.D. Anderson Cancer Center
Southwest Oncology Group
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP