NCT00946712|TerminatedPhase 3ResultsDMC

Study Stopped

terminated at pre-planned futility analysis

S0819: 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)

SWOG Cancer Research Network ClinicalTrials.gov

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5 other identifiers

S0819NCI-2009-01664CDR0000649817U10CA180888U10CA032102

Study Type

interventional

Target

1,333

Locations

2 countries

Sites

798

Timeline

RegisteredJul 2009

StartedJul 2009

CompletionFeb 2022

Brief Summary

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.

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

1,333

participants targeted

Target at P75+ for phase_3

Timeline

Completed

Started Jul 2009

Longer than P75 for phase_3

Geographic Reach

2 countries

798 active sites

Status

terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

12.6 years study duration

Study Start

First participant enrolled

July 15, 2009

Completed

9 days until next milestone

First Submitted

Initial submission to the registry

July 24, 2009

Completed

3 days until next milestone

First Posted

Study publicly available on registry

July 27, 2009

Completed

8.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2017

Completed

1.5 years until next milestone

Results Posted

Study results publicly available

March 7, 2019

Completed

2.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 8, 2022

Completed

Last Updated

May 23, 2023

Status Verified

May 1, 2023

Enrollment Period

8.1 years

First QC Date

July 24, 2009

Results QC Date

December 6, 2018

Last Update Submit

May 19, 2023

Conditions

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

Outcome Measures

Primary Outcomes (2)

Overall Survival (OS) in the Entire Study Population
From date of randomization to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Patients will be followed every 3 weeks while on protocol treatment. Once off all protocol treatment, patients will be followed every 6 months until death or up to 3 years
Progression-free Survival (PFS) of EGFR FISH-positive Patients by Institutional Review
From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, whichever comes first by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as assessed by the treating investigator.Patients last known to be alive and progression-free are censored at date of last contact. Progression is defined using RECIST 1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Disease assessment will be repeated every 6 weeks for the first 9 months and every 3 months thereafter, until disease progression.

Secondary Outcomes (7)

Overall Survival (OS) of EGFR FISH-positive Patients
Patients will be followed every 3 weeks while on protocol treatment. Once off all protocol treatment, patients will be followed every 6 months until death or up to 3 years
Progression-Free Survival (PFS) of EGFR FISH-positive Patients by Centralized Review
Disease assessment will be repeated every 6 weeks until disease progression while on treatment. After off treatment, the frequency of disease assessment may be reduced to every 3 months until disease progression.
Progression-Free Survival (PFS) of the Entire Study Population by Institutional Review
Disease assessment will be repeated every 6 weeks until disease progression while on treatment. After off treatment, the frequency of disease assessment may be reduced to every 3 months until disease progression.
Progression-Free Survival (PFS) of the Entire Study Population by Centralized Review
Disease assessment will be repeated every 6 weeks until disease progression while on treatment. After off treatment, the frequency of disease assessment may be reduced to every 3 months until disease progression.
Response Rate (Confirmed Plus Unconfirmed, Complete and Partial Responses) in the Subset of Patients With Measurable Disease in EGFR FISH-positive Patients
Disease assessment will be repeated every 6 weeks for the first 9 months and every 3 months thereafter, until disease progression.
+2 more secondary outcomes

Study Arms (2)

Arm I (chemo +/- bevacizumab)

EXPERIMENTAL

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.

Biological: BevacizumabDrug: CarboplatinOther: Laboratory Biomarker AnalysisDrug: Paclitaxel

Arm II (chemo, cetuximab, +/- bevacizumab)

EXPERIMENTAL

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.

Biological: BevacizumabDrug: CarboplatinBiological: CetuximabOther: Laboratory Biomarker AnalysisDrug: Paclitaxel

Interventions

BevacizumabBIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, 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

Arm I (chemo +/- bevacizumab)Arm II (chemo, cetuximab, +/- bevacizumab)

CarboplatinDRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplat, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm I (chemo +/- bevacizumab)Arm II (chemo, cetuximab, +/- bevacizumab)

CetuximabBIOLOGICAL

Given IV

Also known as: Chimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux, IMC-C225

Arm II (chemo, cetuximab, +/- bevacizumab)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Arm I (chemo +/- bevacizumab)Arm II (chemo, cetuximab, +/- bevacizumab)

PaclitaxelDRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm I (chemo +/- bevacizumab)Arm II (chemo, cetuximab, +/- bevacizumab)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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)
+15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

SWOG Cancer Research Networklead
National Cancer Institute (NCI)collaborator

Study Sites (798)

Northeast Alabama Regional Medical Center

Anniston, Alabama, 36202, United States

Location

Gulf Coast MBCCOP

Mobile, Alabama, 36604, United States

Location

Providence Hospital

Mobile, Alabama, 36608, United States

Location

Alaska Breast Care and Surgery LLC