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CompletedNCT00368992Updated Sep 14, 2015Results posted

S0536: Cetuximab, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer

A Phase 2 interventional study of cetuximab and paclitaxel in Adenocarcinoma of the Lung, Adenosquamous Cell Lung Cancer and Bronchoalveolar Cell Lung Cancer, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-09-14.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
110
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

Monoclonal antibodies, such as cetuximab and 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 carry tumor-killing substances to them. Cetuximab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab may stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cetuximab together with paclitaxel, carboplatin, and bevacizumab may kill more tumor cells. This phase II trial is studying how well giving cetuximab together with paclitaxel, carboplatin, and bevacizumab works in treating patients with advanced non-small cell lung cancer

Read the detailed description

PRIMARY OBJECTIVES:

I. To evaluate the frequency and severity of hemorrhage toxicities in patients with advanced non-small cell lung cancer treated with the combination of carboplatin, paclitaxel, cetuximab and bevacizumab followed by therapy with cetuximab and bevacizumab.

SECONDARY OBJECTIVES:

I. To evaluate progression-free and overall survival, response rate (confirmed plus unconfirmed, complete plus partial), and frequency and severity of non-hemorrhage toxicities in this group of patients treated with this regimen.

II. To perform molecular correlative studies on patient tissue to investigate in an exploratory manner potential predictors of efficacy.

OUTLINE: This is a multicenter study.

INDUCTION THERAPY: Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive cetuximab IV over 1 hour on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

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

02

Conditions studied

  • Adenocarcinoma of the Lung
  • Adenosquamous Cell Lung Cancer
  • Bronchoalveolar Cell Lung Cancer
  • Large Cell Lung Cancer
  • Recurrent Non-small Cell Lung Cancer
  • Squamous Cell Lung Cancer
  • Stage IIIB Non-small Cell Lung Cancer
  • Stage IV Non-small Cell Lung Cancer
03

In context

Lung Neoplasms

7,243 studies on the registry are indexed under Lung Neoplasms; 1,558 are open to participants now.

This study's enrollment of 110 is above the median of 60 across 5,296 interventional studies indexed under Lung Neoplasms.

Browse Lung Neoplasms studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically proven newly diagnosed selected stage IIIB (T4 lesion due to malignant pleural effusion) or stage IV, advanced primary non-small cell lung cancer (adenocarcinoma, large cell carcinoma, or unspecified) or recurrent disease after previous surgery and/or irradiation; patients with tumors having squamous cell components > 50% are not eligible
  • Patients with known brain metastases are not eligible; all patients must have a pretreatment CT or MRI scan of the brain to evaluate for CNS disease within 42 days prior to registration
  • Patients may have measurable or non-measurable disease documented by CT, MRI, X-ray or physical exam; 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 (Form #848)
  • Patients must not have received any prior systemic chemotherapy or biologic therapy for non-small cell lung cancer; patients must not have received any adjuvant therapy for non-small cell lung cancer
  • Prior radiation is permitted; however, at least three weeks must have elapsed since the completion of prior radiation therapy and patients must have recovered from all associated toxicities at time of registration; measurable or non-measurable disease must be outside the previous radiation field or a new lesion must be present
  • At least four weeks must have elapsed since surgery (thoracic or other major surgeries) and patients must have recovered from all associated toxicities at the time of registration; measurable disease must be present outside the area of surgical resection; there must be no anticipation of need for major surgical procedures during protocol treatment
  • Patients must not have received prior cetuximab, ZD1839, erlotinib or other investigational agents that target the EGFR pathway; patients must not have received prior VEGF-related agents; patients must not have received prior chimerized or murine monoclonal antibody therapy or have documented presence of human anti-mouse antibodies (HAMA)
  • ANC >= 1,500/mcl
  • Platelet count >= 100,000/mcl
  • Hemoglobin >= 9 mg/dl
  • Patients must have a serum creatinine =\< institutional upper limit of normal (IULN) AND calculated or measured creatinine clearance >= 50 cc/min using the Cockroft-Gault Formula
  • 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
  • Serum bilirubin =\< 2 x IULN
  • Either SGOT or SGPT =\< 2 x IULN (if both SGOT and SGPT are done, both must be =\< 2 x IULN)
  • International Normalized Ratio (INR) =\< 1.5; patients must not be taking full-dose anticoagulation therapy; patients may be enrolled initially if they are on low-dose warfarin (i.e., 1 mg daily)
  • All patients must have a Zubrod performance status of 0 - 1
  • Correlative science studies: institutions must have received IRB approval of S9925 (the Lung Cancer Specimen Repository); patients must be offered participation in S9925; with the patient's consent, blood, plasma and tissue will be submitted for testing via S9925; patients must be registered separately to S9925 in order for institutions to receive credit for specimen submissions
  • Patients must not have had hemoptysis >= 1/2 teaspoon within 3 months prior to registration
  • 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 CVA, myocardial infarction or unstable angina; 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 not have had an open biopsy or significant traumatic injury within 28 days prior to registration; patients must not have had a core biopsy within 7 days prior to registration
  • Patients must not have serious or non-healing wound, ulcer or bone fracture
  • Patients must not have history of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 28 days prior to registration
  • Patients must have no known hypersensitivity of Chinese hamster ovary cell products or other recombinant human antibodies
  • Patients must not have evidence of bleeding diathesis or coagulopathy
  • Patients must be willing to provide prior smoking history as required on the S0536 Prestudy Form (Form #54655)
  • No other prior malignancy is allowed except for 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, or any other cancer from which the patient has been disease-free for 5 years
  • Pregnant or nursing women are not eligible for this trial; women/men of reproductive potential must not participate unless they have agreed to use an effective contraceptive method during protocol treatment and for at least 6 months following completion of bevacizumab treatment
  • Patients 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
  • At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
110 participants (actual)

Study arms

  • Experimental
    Treatment (cetuximab, paclitaxel, bevacizumab)

    INDUCTION THERAPY: Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive cetuximab IV over 1 hour on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

    Biological: cetuximab · Drug: paclitaxel · Biological: bevacizumab

Interventions

  • Biologicalcetuximab

    Given IV

    Also known as: C225, C225 monoclonal antibody, IMC-C225, MOAB C225, monoclonal antibody C225

  • Drugpaclitaxel

    Given IV

    Also known as: Anzatax, Asotax, TAX, Taxol

  • Biologicalbevacizumab

    Given IV

    Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

06

What researchers measure

Primary outcomes

  1. The Percentage of Patients With Grade 4 (i.e. Life-threatening) Hemorrhage Toxicities Related to Protocol Treatment.

    All patients who received protocol treatment were assessed for adverse events per the NCI Common Terminology Criteria for Adverse Events, Version 3.0. We counted the number of patients who reported at least one Grade 4 (i.e. life-threatening) hemorrhage adverse event that was possibly, probably, or definitely related to the study treatment.

    Time frame: Every week until removed from protocol therapy, up to 3 years.

Secondary outcomes

  1. Progression-Free Survival

    From data of registration to date of disease progression (as defined by RECIST, i.e. a 20% increase in the sum of the longest diameters of target lesions, or unequivocal progression ina non-target lesion in the opinion of the treating investigator, or the appearance of new lesions), symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free were censored at the date of last contact.

    Time frame: Every 6 weeks until disease progression. After 9 months, every 12 weeks until disease progression, up to 3 years.

  2. Overall Survival

    From date of enrollment to date of death due to any cause. Patients last known to be alive were censored at date of last contact.

    Time frame: Once a week, up to 3 years.

  3. Response Rate

    Confirmed and unconfirmed complete and partial responses per RECIST in the subset of patients with at least one target lesion assessed by CT or MRI. A complete response (CR) was defined as disappearance of all disease, including non-target lesions. A partial response (PR) was defined as a \>= 30% decrease in the sum of the longest diameters of all target lesions. A CR or PR was confirmed if documented a second time at least 4 weeks after the first documentation.

    Time frame: Every 6 weeks while on protocol treatment, up to 3 years.

07

Results

Posted Sep 14, 2015

Participant flow

Participant flow — Overall Study
MilestoneCarboplatin, Paclitaxel, Cetuximab, and Bevacizumab
Started110
Completed0
Not completed110
Withdrew: Ineligible5
Withdrew: Refused treatment3
Withdrew: Lack of efficacy63
Withdrew: Adverse event26
Withdrew: Death4
Withdrew: Other9

Outcome measures

PrimaryThe Percentage of Patients With Grade 4 (i.e. Life-threatening) Hemorrhage Toxicities Related to Protocol Treatment.

All patients who received protocol treatment were assessed for adverse events per the NCI Common Terminology Criteria for Adverse Events, Version 3.0. We counted the number of patients who reported at least one Grade 4 (i.e. life-threatening) hemorrhage adverse event that was possibly, probably, or definitely related to the study treatment.

Time frame:
Every week until removed from protocol therapy, up to 3 years.
Reported as:
Number · percentage of participants
The Percentage of Patients With Grade 4 (i.e. Life-threatening) Hemorrhage Toxicities Related to Protocol Treatment.
percentage of participantsCarboplatin, Paclitaxel, Cetuximab, and Bevacizumab
The Percentage of Patients With Grade 4 (i.e. Life-threatening) Hemorrhage Toxicities Related to Protocol Treatment.2 (0 to 7)
SecondaryProgression-Free Survival

From data of registration to date of disease progression (as defined by RECIST, i.e. a 20% increase in the sum of the longest diameters of target lesions, or unequivocal progression ina non-target lesion in the opinion of the treating investigator, or the appearance of new lesions), symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free were censored at the date of last contact.

Time frame:
Every 6 weeks until disease progression. After 9 months, every 12 weeks until disease progression, up to 3 years.
Reported as:
Median · Months
Progression-Free Survival
MonthsCarboplatin, Paclitaxel, Cetuximab, and Bevacizumab
Progression-Free Survival7 (6 to 8)
SecondaryOverall Survival

From date of enrollment to date of death due to any cause. Patients last known to be alive were censored at date of last contact.

Time frame:
Once a week, up to 3 years.
Reported as:
Median · months
Overall Survival
monthsCarboplatin, Paclitaxel, Cetuximab, and Bevacizumab
Overall Survival15 (11 to 21)
SecondaryResponse Rate

Confirmed and unconfirmed complete and partial responses per RECIST in the subset of patients with at least one target lesion assessed by CT or MRI. A complete response (CR) was defined as disappearance of all disease, including non-target lesions. A partial response (PR) was defined as a \>= 30% decrease in the sum of the longest diameters of all target lesions. A CR or PR was confirmed if documented a second time at least 4 weeks after the first documentation.

Time frame:
Every 6 weeks while on protocol treatment, up to 3 years.
Reported as:
Number · percentage of participants
Response Rate
percentage of participantsCarboplatin, Paclitaxel, Cetuximab, and Bevacizumab
Response Rate56 (44 to 65)

Adverse events

Collected over Weekly while on protocol treatment.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Carboplatin, Paclitaxel, Cetuximab, and Bevacizumab—51/102 (50%)101/102 (99%)
Most frequent serious events
Showing 10 of 66
Most frequent serious events
EventCarboplatin, Paclitaxel, Cetuximab, and Bevacizumab
Neutrophils/granulocytes (ANC/AGC)Investigations16/102
Dyspnea (shortness of breath)Respiratory, thoracic and mediastinal disorders9/102
DehydrationMetabolism and nutrition disorders7/102
Thrombosis/thrombus/embolismVascular disorders7/102
Fatigue (asthenia, lethargy, malaise)General disorders6/102
Febrile neutropeniaBlood and lymphatic system disorders5/102
NauseaGastrointestinal disorders5/102
Inf (clin/microbio) w/Gr 3-4 neuts - LungInfections and infestations4/102
Pneumonitis/pulmonary infiltratesRespiratory, thoracic and mediastinal disorders4/102
Inf w/normal ANC or Gr 1-2 neutrophils - LungInfections and infestations3/102
Most frequent other events
Showing 10 of 75
Most frequent other events
EventCarboplatin, Paclitaxel, Cetuximab, and Bevacizumab
Fatigue (asthenia, lethargy, malaise)General disorders88/102
Rash: acne/acneiformSkin and subcutaneous tissue disorders78/102
Neuropathy: sensoryNervous system disorders76/102
Neutrophils/granulocytes (ANC/AGC)Investigations62/102
HemoglobinBlood and lymphatic system disorders58/102
ConstipationGastrointestinal disorders57/102
Glucose, serum-high (hyperglycemia)Metabolism and nutrition disorders56/102
NauseaGastrointestinal disorders53/102
Leukocytes (total WBC)Investigations52/102
Magnesium, serum-low (hypomagnesemia)Metabolism and nutrition disorders50/102

Baseline characteristics

Age, Continuous
Age, Continuous(years)Carboplatin, Paclitaxel, Cetuximab, and Bevacizumab
Median64 (42 to 78)
Sex: Female, Male
Sex: Female, Male(Participants)Carboplatin, Paclitaxel, Cetuximab, and Bevacizumab
Female50
Male52
08

Study locations

1 site
  • Southwest Oncology Group
    San Antonio, Texas 78245, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 14, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00368992
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Aug 29, 2006
Start date
Aug 2006
Primary completion
Oct 2010
Completion
Oct 2010
Results posted
Sep 14, 2015
Last update
Sep 14, 2015

Study contacts

Edward Kim
principal investigator · SWOG Cancer Research Network
View the source record on ClinicalTrials.gov ↗

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