Trial record 1 of 1 for:    SWOG 0819
Previous Study | Return to List | Next Study

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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00946712
First received: July 24, 2009
Last updated: September 1, 2015
Last verified: September 2015

July 24, 2009
September 1, 2015
July 2009
February 2017   (final data collection date for primary outcome measure)
  • Overall survival (OS) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) of EGFR FISH-positive patients by institutional review [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    A stratified log-rank test will be used.
  • 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
  • Incidence of toxicity as assessed by NCI CTCAE version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • OS of EGFR FISH-positive patients by centralized review [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    A stratified log-rank test will be used.
  • PFS of EGFR FISH-positive patients by centralized review [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • PFS of the entire study population by centralized review and by institutional review [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Response [ Time Frame: Up to 3 years ] [ 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
 
Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With 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)

This randomized phase III trial studies carboplatin and paclitaxel to compare how well they work with or without bevacizumab and/or cetuximab in treating patients with stage IV or non-small cell lung cancer that has returned after a period of improvement (recurrent). 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, by stopping them from dividing, or by stopping them from spreading. Bevacizumab may prevent the growth of new blood vessels that tumor needs to grow. Cetuximab may also stop cancer cells from growing by binding and interfering with a protein on the surface of the tumor cell that is needed for tumor growth. 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.

PRIMARY OBJECTIVES:

I. To compare overall survival (OS) in the entire study population. II. To compare progression-free survival (PFS) by institutional review of epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH)-positive patients.

SECONDARY OBJECTIVES:

I. To compare OS and PFS by centralized review in EGFR FISH-positive patients. II. To compare PFS by centralized image review and by institutional review in the entire study population.

III. To compare the response rate (confirmed plus unconfirmed, complete and partial responses) in a subset of patients with measurable disease in EGFR FISH-positive patient and the entire study population.

IV. To assess the toxicities of these treatment regimens. V. To prospectively test EGFR FISH as a predictive marker for the selection of patients for cetuximab plus chemotherapy.

III. To evaluate the role of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in terms of cetuximab efficacy.

IV. To compare the results of EGFR FISH with KRAS mutations, EGFR mutations, EGFR immunohistochemistry (IHC), and other purported EGFR-related biomarkers.

TERTIARY OBJECTIVES:

I. To compare PFS in patients with advanced non-small cell lung cancer (NSCLC) with an IHC score > 200 treated with carboplatin, paclitaxel, and bevacizumab (if appropriate) with or without cetuximab.

II. 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: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes 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 paclitaxel and carboplatin 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.

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
  • Recurrent Large Cell Lung Carcinoma
  • Recurrent Lung Adenocarcinoma
  • Recurrent Squamous Cell Lung Carcinoma
  • Stage IV Large Cell Lung Carcinoma
  • Stage IV Lung Adenocarcinoma
  • Stage IV Squamous Cell Lung Carcinoma
  • Biological: Bevacizumab
    Given IV
    Other Names:
    • Anti-VEGF
    • Anti-VEGF Humanized Monoclonal Antibody
    • Anti-VEGF rhuMAb
    • Avastin
    • BEVACIZUMAB
    • Bevacizumab Biosimilar BEVZ92
    • Bevacizumab Biosimilar BI 695502
    • Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
    • Recombinant Humanized Anti-VEGF Monoclonal Antibody
    • rhuMab-VEGF
  • Drug: Carboplatin
    Given IV
    Other Names:
    • Blastocarb
    • Carboplat
    • CARBOPLATIN
    • Carboplatin Hexal
    • Carboplatino
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplat
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Biological: Cetuximab
    Given IV
    Other Names:
    • CETUXIMAB
    • Chimeric Anti-EGFR Monoclonal Antibody
    • Chimeric MoAb C225
    • Chimeric Monoclonal Antibody C225
    • Erbitux
    • IMC-C225
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Paclitaxel
    Given IV
    Other Names:
    • Anzatax
    • Asotax
    • Bristaxol
    • PACLITAXEL
    • Praxel
    • Taxol
    • Taxol Konzentrat
  • Experimental: Arm I (chemo +/- bevacizumab)
    Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes 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
    • Other: Laboratory Biomarker Analysis
    • Drug: Paclitaxel
  • Experimental: Arm II (chemo, cetuximab, +/- bevacizumab)
    Patients receive paclitaxel and carboplatin 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
    • Drug: Carboplatin
    • Biological: Cetuximab
    • Other: Laboratory Biomarker Analysis
    • Drug: Paclitaxel
Not Provided

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

Inclusion Criteria:

  • Patients must have histologically or cytologically proven primary non-small cell lung cancer (adenocarcinoma, large cell carcinoma, squamous or unspecified); disease must be stage IV; disease may be either newly diagnosed or recurrent after previous surgery and/or irradiation; patients with additional lesions in an ipsilateral non-primary lobe without M1a or M1b disease will not be considered to have stage IV disease and are not eligible
  • Patients must have a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to registration; patient must not have brain metastases unless: (1) metastases have been treated and have remained controlled for at least two weeks following treatment, AND (2) patient has no residual neurological dysfunction off corticosteroids for at least 1 day
  • Patients may have measurable or non-measurable disease documented by CT or MRI; the CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality; measurable disease must be assessed within 28 days prior to registration; pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease; non-measurable disease must be assessed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form
  • Patients must have tumor tissue available for submission that is sufficient for EGFR FISH testing and must agree to submission of these specimens; patients must also agree to submission of specimens for other translational medicine studies; patient must be offered participation in banking for future research
  • Patients must not have received prior chemotherapy for any stage non-small cell lung cancer; patients must not have received prior platinum-based chemotherapy for any purpose; patient must not have received any cetuximab, gefitinib, erlotinib, or other investigational agents that target the EGFR pathway; patients must not have received for any purpose prior bevacizumab or other vascular endothelial growth factor (VEGF)-related agents; patients must not have received for any purpose prior chimerized or murine monoclonal antibody therapy or have documented presence of human anti-mouse antibodies (HAMA)
  • Prior radiation is permitted; however, patients must have recovered from all associated toxicities at time of registration; in order to qualify as measurable, measurable disease must be outside the previous radiation field or must have progressed
  • Time from surgical or biopsy procedures is dependent on whether it is planned for the patient to receive bevacizumab

    • For patients who are bevacizumab-appropriate AND bevacizumab is planned: at least 28 days must have elapsed since major surgery (i.e. thoracotomy or video-assisted thoracoscopic surgery [VATS] resection of lung cancer, open pleural biopsy or another major surgical procedure such as abdominal surgery) or significant traumatic injury; patients must have recovered from all associated toxicities at the time of registration; there must be no anticipation of need for major surgical procedures during protocol treatment; patients must not have had a core biopsy, mediastinoscopy, pleurodesis, VATS pleural biopsy or VATS pericardial window within 14 days prior to registration; patients must not have had a percutaneous fine needle aspiration (FNA), thoracentesis or central venous access device implanted within 7 days prior to registration; for other surgical procedures not listed here, please contact the study coordinators
    • For patients who are bevacizumab-inappropriate or bevacizumab is not planned: at least 28 days must have elapsed since major surgery (i.e. thoracotomy or VATS resection of lung cancer, open pleural biopsy or another major surgical procedure such as abdominal surgery) or significant traumatic injury; patients must have recovered from all associated toxicities at the time of registration; there must be no anticipation of need for major surgical procedures during protocol treatment; patients must not have had a core biopsy, mediastinoscopy, pleurodesis, VATS pleural biopsy or VATS pericardial window within 7 days prior to registration; patients must not have had a percutaneous fine needle aspiration (FNA), or thoracentesis within 1 day prior to registration; patients may have had a central venous access device placed at any time prior to registration; for other surgical procedures not listed here, please contact the study coordinators
  • Absolute neutrophil count (ANC) >= 1,500/mcl
  • Platelet count >= 100,000/mcl
  • Hemoglobin >= 9 g/dL
  • Serum creatinine =< institutional upper limit of normal (IULN) AND calculated or measured creatinine clearance >= 50 cc/min using the following Cockroft-Gault formula
  • For patients who will be receiving bevacizumab, urine protein must be screened by urine analysis for urine protein creatinine (UPC) ratio; for UPC ratio > 0.5, 24-hour urine protein must be obtained and the level must be < 1,000 mg for patient enrollment; the urine protein used to calculate the UPC ratio must be obtained within 14 days prior to registration; UPC or 24-hour protein is not required for patients who will not receive bevacizumab Note: UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
  • Serum bilirubin =< 2 times IULN (for patients with liver metastases, bilirubin must be =< 5 X IULN)
  • Serum glutamic oxaloacetic transaminase (SGOT) OR serum glutamate pyruvate transaminase (SGPT) =< 2 times IULN (for patients with liver metastases, either SGOT or SGPT must be =< 5 X IULN)
  • Zubrod performance status 0-1
  • Patients must not have >= grade 2 symptomatic neuropathy-sensory (National Cancer Institute [NCI] Common Terminology Criteria version 3.0)
  • Patients must not have documented evidence of acute hepatitis or have an active or uncontrolled infection
  • Patients must not have the following: history (within past 6 months) of cerebrovascular accident (CVA), myocardial infarction or unstable angina; or at the time of registration, uncontrolled hypertension, New York Heart Association grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or clinically significant peripheral vascular disease
  • Patients must have no known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (examples include trastuzumab [Herceptin] and epoetin alpha)
  • Patients must be willing to provide prior smoking history
  • No other prior malignancy is allowed 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
  • Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
  • Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Mexico
 
NCT00946712
S0819, NCI-2009-01664, CDR0000649817, S0819, S0819, U10CA180888, U10CA032102
Yes
Southwest Oncology Group
Southwest Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Roy Herbst Southwest Oncology Group
Southwest Oncology Group
September 2015

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