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NCT00946712

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

Terminated Phase 3 Results posted Last updated 23 May 2023
What this trial tests

Phase 3 trial testing Bevacizumab in Recurrent Large Cell Lung Carcinoma in 1,333 participants. Terminated before completion.

Timeline
15 July 2009
Primary endpoint
31 August 2017
8 February 2022

Quick facts

Lead sponsorSWOG Cancer Research Network
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment1,333
Start date15 July 2009
Primary completion31 August 2017
Estimated completion8 February 2022
Sites798 locations across United States, Mexico

Drugs / interventions tested

Conditions studied

Sponsor

SWOG Cancer Research Network

Who can join

18 and older, any sex, with Recurrent Large Cell Lung Carcinoma or Recurrent Lung Adenocarcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Survival (OS) in the Entire Study Population Primary · 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

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.

GroupValue95% CI
Arm I (Chemo +/- Bevacizumab)9.28.7 – 10.3
Arm II (Chemo, Cetuximab, +/- Bevacizumab)10.99.5 – 12.0
Progression-free Survival (PFS) of EGFR FISH-positive Patients by Institutional Review Primary · Disease assessment will be repeated every 6 weeks for the first 9 months and every 3 months thereafter, until disease progression.

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.

GroupValue95% CI
Arm I (Chemo +/- Bevacizumab)4.83.9 – 5.5
Arm II (Chemo, Cetuximab, +/- Bevacizumab)5.44.5 – 5.7
Overall Survival (OS) of EGFR FISH-positive Patients Secondary · 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

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.

GroupValue95% CI
Arm I (Chemo +/- Bevacizumab)9.88.7 – 12.1
Arm II (Chemo, Cetuximab, +/- Bevacizumab)13.411.5 – 14.8
Progression-Free Survival (PFS) of the Entire Study Population by Institutional Review Secondary · 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.

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.

GroupValue95% CI
Arm I (Chemo +/- Bevacizumab)4.54.2 – 5.1
Arm II (Chemo, Cetuximab, +/- Bevacizumab)4.64.2 – 5.2
Response Rate (Confirmed Plus Unconfirmed, Complete and Partial Responses) in the Subset of Patients With Measurable Disease in EGFR FISH-positive Patients Secondary · Disease assessment will be repeated every 6 weeks for the first 9 months and every 3 months thereafter, until disease progression.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

GroupValue95% CI
Arm I (Chemo +/- Bevacizumab)4336 – 50
Arm II (Chemo, Cetuximab, +/- Bevacizumab)4739 – 54
Response Rate (Confirmed Plus Unconfirmed, Complete and Partial Responses) in the Subset of Patients With Measurable Disease in the Entire Study Population Secondary · Disease assessment will be repeated every 6 weeks for the first 9 months and every 3 months thereafter, until disease progression.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

GroupValue95% CI
Arm I (Chemo +/- Bevacizumab)3633 – 40
Arm II (Chemo, Cetuximab, +/- Bevacizumab)4238 – 46
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Secondary · Toxicity assessment was evaluated every 3 weeks while one protocol treatment. Chemo and cetuximab is treated for 6 cycles (1 cycle =3 weeks) and Bevacizumab is treated until progression or unacceptable toxicity.

Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.

ALT, SGPT (serum glutamic pyruvic transaminase)
GroupValue95% CI
Arm I (Chemo +/- Bevacizumab)5
Arm II (Chemo, Cetuximab, +/- Bevacizumab)8
AST, SGOT
GroupValue95% CI
Arm I (Chemo +/- Bevacizumab)6
Arm II (Chemo, Cetuximab, +/- Bevacizumab)8
Acidosis (metabolic or respiratory)
GroupValue95% CI
Arm I (Chemo +/- Bevacizumab)0
Arm II (Chemo, Cetuximab, +/- Bevacizumab)1
Adrenal insufficiency
GroupValue95% CI
Arm I (Chemo +/- Bevacizumab)0
Arm II (Chemo, Cetuximab, +/- Bevacizumab)1
Albumin, serum-low (hypoalbuminemia)
GroupValue95% CI
Arm I (Chemo +/- Bevacizumab)8
Arm II (Chemo, Cetuximab, +/- Bevacizumab)7
Alkaline phosphatase
GroupValue95% CI
Arm I (Chemo +/- Bevacizumab)2
Arm II (Chemo, Cetuximab, +/- Bevacizumab)1
Allergic reaction/hypersensitivity
GroupValue95% CI
Arm I (Chemo +/- Bevacizumab)9
Arm II (Chemo, Cetuximab, +/- Bevacizumab)41
Allergy/Immunology-Other (Specify)
GroupValue95% CI
Arm I (Chemo +/- Bevacizumab)0
Arm II (Chemo, Cetuximab, +/- Bevacizumab)2

Adverse events — posted to ClinicalTrials.gov

Time frame: Toxicity assessment was evaluated every 3 weeks while on protocol treatment. Chemo and cetuximab is treated for 6 cycles (1 cycle =3 weeks) and Bevacizumab is treated until progression, an average of 6 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm I (Chemo +/- Bevacizumab)
Serious: 66/632 (10%)
Deaths: 593/657
Arm II (Chemo, Cetuximab, +/- Bevacizumab)
Serious: 97/627 (15%)
Deaths: 570/656

Serious adverse events (75 terms)

ReactionSystemArm I (Chemo +/- Bevacizum…Arm II (Chemo, Cetuximab, …
Death - Disease progression NOSNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Death not associated with CTCAE term - Death NOSGeneral disorders
Allergic reaction/hypersensitivityImmune system disorders
Carbon monoxide diffusion capacity (DL(co))Investigations
Carbon monoxide diffusion capacity (DL(co))Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)Respiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
Inf (clin/microbio) w/Gr 3-4 neuts - BloodInfections and infestations
Perforation, GI - ColonGastrointestinal disorders
HypotensionVascular disorders
Thrombosis/thrombus/embolismVascular disorders
Cardiac General-OtherCardiac disorders
Cytokine release syndrome/acute infusion reactionImmune system disorders
PlateletsInvestigations
Sodium, serum-low (hyponatremia)Metabolism and nutrition disorders
CNS cerebrovascular ischemiaNervous system disorders
Pleural effusion (non-malignant)Respiratory, thoracic and mediastinal disorders
HemoglobinBlood and lymphatic system disorders
Cardiac-ischemia/infarctionCardiac disorders
Cardiopulmonary arrest, cause unknown (non-fatal)Cardiac disorders
SVT and nodal arrhythmia - Atrial fibrillationCardiac disorders
Gastrointestinal-OtherGastrointestinal disorders
Death - Multi-organ failureGeneral disorders
Inf w/normal ANC or Gr 1-2 neutrophils - LungInfections and infestations
Infection with unknown ANC - BloodInfections and infestations
Other adverse events (73 terms — click to expand)

ReactionSystemArm I (Chemo +/- Bevacizum…Arm II (Chemo, Cetuximab, …
Fatigue (asthenia, lethargy, malaise)General disorders
HemoglobinBlood and lymphatic system disorders
Rash: acne/acneiformSkin and subcutaneous tissue disorders
Neuropathy: sensoryNervous system disorders
Magnesium, serum-low (hypomagnesemia)Metabolism and nutrition disorders
NauseaGastrointestinal disorders
Hair loss/Alopecia (scalp or body)Skin and subcutaneous tissue disorders
Neutrophils/granulocytes (ANC/AGC)Investigations
ConstipationGastrointestinal disorders
Glucose, serum-high (hyperglycemia)Metabolism and nutrition disorders
Dyspnea (shortness of breath)Respiratory, thoracic and mediastinal disorders
Leukocytes (total WBC)Investigations
PlateletsInvestigations
CoughRespiratory, thoracic and mediastinal disorders
AnorexiaMetabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)Metabolism and nutrition disorders
DiarrheaGastrointestinal disorders
Dry skinSkin and subcutaneous tissue disorders
Sodium, serum-low (hyponatremia)Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)Metabolism and nutrition disorders
Pain - JointMusculoskeletal and connective tissue disorders
Weight lossInvestigations
Calcium, serum-low (hypocalcemia)Metabolism and nutrition disorders
Alkaline phosphataseInvestigations
VomitingGastrointestinal disorders
DizzinessNervous system disorders
LymphopeniaInvestigations
Mucositis/stomatitis (clinical exam) - Oral cavityGastrointestinal disorders
Pain - MuscleMusculoskeletal and connective tissue disorders
Rash/desquamationSkin and subcutaneous tissue disorders
Pain - Extremity-limbMusculoskeletal and connective tissue disorders
ALT, SGPT (serum glutamic pyruvic transaminase)Investigations
Taste alteration (dysgeusia)Nervous system disorders
AST, SGOTInvestigations
InsomniaPsychiatric disorders
Pain - BackMusculoskeletal and connective tissue disorders
HypertensionVascular disorders
Muscle weakness, not d/t neuropathy - body/generalMusculoskeletal and connective tissue disorders
Pruritus/itchingSkin and subcutaneous tissue disorders
DehydrationMetabolism and nutrition disorders

Most-reported serious reactions: Death - Disease progression NOS, Death not associated with CTCAE term - Death NOS, Allergic reaction/hypersensitivity, Carbon monoxide diffusion capacity (DL(co)), Carbon monoxide diffusion capacity (DL(co)), Dyspnea (shortness of breath), Febrile neutropenia, Inf (clin/microbio) w/Gr 3-4 neuts - Blood.

Data from ClinicalTrials.gov NCT00946712 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeted therapy in cancer.
    Tsimberidou AM. · · 2015 · cited 156× · PMID 26391154 · DOI 10.1007/s00280-015-2861-1
  2. Cetuximab and bevacizumab: preclinical data and phase II trial in recurrent or metastatic squamous cell carcinoma of the head and neck.
    Argiris A, Kotsakis AP, Hoang T, Worden FP, et al · · 2013 · cited 106× · PMID 22898037 · DOI 10.1093/annonc/mds245
  3. Targeted therapy for non-small-cell lung cancer: past, present and future.
    Forde PM, Ettinger DS. · · 2013 · cited 84× · PMID 23773106 · DOI 10.1586/era.13.47
  4. Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study.
    Herbst RS, Redman MW, Kim ES, Semrad TJ, et al · · 2018 · cited 66× · PMID 29169877 · DOI 10.1016/s1470-2045(17)30694-0
  5. Targeted therapies in development for non-small cell lung cancer.
    Reungwetwattana T, Dy GK. · · 2013 · cited 59× · PMID 24574860 · DOI 10.4103/1477-3163.123972
  6. Antiangiogenic agents in combination with chemotherapy in patients with advanced non-small cell lung cancer.
    Ulahannan SV, Brahmer JR. · · 2011 · cited 58× · PMID 21469981 · DOI 10.3109/07357907.2011.554476
  7. Design of a phase III clinical trial with prospective biomarker validation: SWOG S0819.
    Redman MW, Crowley JJ, Herbst RS, Hirsch FR, et al · · 2012 · cited 36× · PMID 22592956 · DOI 10.1158/1078-0432.ccr-12-0167
  8. Importance of molecular features of non-small cell lung cancer for choice of treatment.
    Moran C. · · 2011 · cited 34× · PMID 21514411 · DOI 10.1016/j.ajpath.2010.12.057

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00946712.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing