Brief Title
S0536: Cetuximab, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer
Official Title
A Phase II Trial of Combination Carboplatin, Paclitaxel, Cetuximab and Bevacizumab (NSC-704865) Followed By Cetuximab and Bevacizumab in Patients With Advanced Non-Small Cell Lung Cancer
Brief 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
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
The Percentage of Patients With Grade 4 (i.e. Life-threatening) Hemorrhage Toxicities Related to Protocol Treatment.
Secondary Outcome
Progression-Free Survival
Condition
Adenocarcinoma of the Lung
Intervention
cetuximab
Study Arms / Comparison Groups
Treatment (cetuximab, paclitaxel, bevacizumab)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
110
Start Date
August 2006
Completion Date
October 2010
Primary Completion Date
October 2010
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Edward Kim, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00368992
Organization ID
NCI-2012-02903
Secondary IDs
S0536
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Edward Kim, Principal Investigator, Southwest Oncology Group
Verification Date
February 2013