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Phase II Trial of Bevacizumab and Ixabepilone for Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Progressive After First-line Therapy


Phase 2
18 Years
N/A
Not Enrolling
Both
Non-squamous Non-small Cell Lung Cancer

Thank you

Trial Information

Phase II Trial of Bevacizumab and Ixabepilone for Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Progressive After First-line Therapy


The first six patients will be enrolled in a lead-in phase of the study utilizing a reduced
dose of ixabepilone. Patients will be monitored for safety and toxicity. If the
combination is found to be tolerable and feasible, accrual will continue with the full-dose
regimen. Toxicity will be monitored in real-time by the study investigators. Should
unexpected or increased toxicity be detected, trial accrual will be halted for full
analysis.

Bevacizumab will be administered intravenously, 10 mg/kg, every two weeks. Ixabepilone will
be administered intravenously, 16 mg/m2, once weekly for 3 of 4 weeks on a 28-day schedule,
to the first six patients enrolled. Ixabepilone will be administered intravenously,
20mg/m2, once weekly for 3 of 4 weeks on a 28-day schedule, to the remaining 40 patients
enrolled.


Inclusion Criteria:



- Histologic or cytologic diagnosis of advanced or metastatic non-small cell lung
cancer (NSCLC), excluding squamous cell-predominant subtype. NSCLC NOS (not
otherwise specified) are eligible.

- Patients must have had at least one but no more than two prior systemic
chemotherapeutic regimens for metastatic disease. Prior neoadjuvant or adjuvant
chemotherapy will not be included in the assessment as a prior chemotherapeutic
regimen. Prior therapy with taxanes is allowed. Prior therapy with bevacizumab is
allowed.

- Prior chemotherapy or therapy with investigational agents must have been completed at
least 3 weeks prior to study enrollment.

- Zubrod performance status of 0 or 1.

- Patients must have measurable or evaluable disease as defined by RECIST.

- Treated brain metastases will be allowed, provided they are asymptomatic. Radiation
treatment for brain metastasis must have been completed at least 2 weeks prior to
enrollment. Patients must demonstrate stable symptoms and seizure control on a
consistent dose of anticonvulsants for at least 2 weeks prior to enrollment. Patients
must be off corticosteroids for at least 2 weeks. Treatment for brain metastases may
include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, KINAC, or
equivalent) or a combination as deemed appropriate by the treating physician.
Patients with CNS metastases treated by neurosurgical resection or brain biopsy
performed within 3 months prior to Day 1 will be excluded.

- Radiation for symptomatic lesions outside the CNS must have been completed at least 2
weeks prior to study enrollment. If measurable disease is within the radiation
field, there must be evidence of clear progression (using RECIST criteria) at the
time of study enrollment.

- Major surgical procedures must have been performed >28 days prior to study treatment.
Portacath placement must have been performed >14 days prior to study treatment.
Minor surgical procedures (fine needle aspiration, core biopsy, or mediastinoscopy)
must have been performed >7 days prior to study treatment.

- Patients must have normal organ and marrow function as defined below:

- leukocytes > 3,000/uL

- absolute neutrophil count > 1,500/uL

- platelets > 100,000/uL

- total bilirubin within normal institutional limits

- AST (SGOT)/ALT (SGPT) < 2.5 X institutional upper limit of normal

- creatinine < 1.5 mg/dL, OR

- calculated creatinine clearance > 40 mL/min

- Estimated life expectancy of greater than 12 weeks.

- Patients must be able to sign informed consent.

- Patients must be >18 years of age. Both men and women and members of all races and
ethnic groups will be included.

- Patients must either not be of child bearing potential or, if female, have a negative
serum pregnancy test within 72 hours prior to Day 1. Patients are considered not of
child bearing potential if they are surgically sterile (they have undergone a
vasectomy, hysterectomy, bilateral tubal ligation, bilateral oophorectomy) or they
are postmenopausal with no menses for at least 12 months. Patients of childbearing
potential must be willing to use adequate barrier contraception for the duration of
study participation and at least 30 days after study completion.

Exclusion Criteria:

- NSCLC with predominant squamous cell histology (mixed tumors will be categorized by
the predominant cell type unless small cell elements are present, in which case the
patient is ineligible; sputum cytology alone is not acceptable).

- History of hemoptysis (bright red blood of 1/2 teaspoon or more per episode) within 1
month prior to Day 1.

- Known CNS disease, except for treated brain metastasis. Treated brain metastases are
defined as having no evidence of progression or hemorrhage after treatment and no
ongoing requirement for dexamethasone (within the last two weeks prior to Day 1), as
ascertained by clinical examination and brain imaging (MRI or CT) during the
screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain
metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma
Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating
physician. Patients with CNS metastases treated by neurosurgical resection or brain
biopsy performed within 3 months prior to Day 1 will be excluded.

- Inability to comply with study and/or follow-up procedures.

- An investigational agent within 3 weeks of Day 1.

- Patients with greater than grade 1 neuropathy.

- Pregnant (positive pregnancy test) or lactating.

- Serious concomitant medical disorder, including active infection.

- Active second primary malignancy at the time of study enrollment.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ixabepilone or Cremophor EL (polyoxyethylated castor oil).

- History of co-existing psychiatric illness that could impair compliance with study
protocol.

- Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or
diastolic blood pressure > 100 mmHg on antihypertensive medications).

- Any prior history of hypertensive crisis or hypertensive encephalopathy.

- New York Heart Association (NYHA) Grade II or greater congestive heart failure.

- History of myocardial infarction or unstable angina within 6 months prior to Day 1.

- History of stroke or transient ischemic attack within 6 months prior to Day 1 of
treatment.

- Significant vascular disease (e.g., aortic aneurysm, aortic dissection).

- Symptomatic peripheral vascular disease.

- Evidence of bleeding diathesis or significant coagulopathy (in the absence of
therapeutic anticoagulation).

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 1 or anticipation of need for major surgical procedure during the course
of the study.

- Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device, within 7 days prior to Day 1.

- Portacath placement within 14 days prior to Day 1.

- History of abdominal fistula or gastrointestinal perforation within 6 months prior to
Day 1.

- Serious, non-healing wound, active ulcer, or untreated bone fracture.

- Proteinuria at screening as demonstrated by either:

- Urine protein: creatinine (UPC) ratio ≥ 1.0 at screening OR

- Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria
on dipstick urinalysis at screening should undergo a 24 hour urine collection
and must demonstrate ≤ 500 mg of protein in 24 hours to be eligible).

- Known hypersensitivity to any component of bevacizumab.

- Prior discontinuation of bevacizumab due to treatment-related toxicity.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

progression-free survival

Outcome Time Frame:

at week 8, week 16, and every 8 weeks until disease progression or removal from study

Safety Issue:

No

Principal Investigator

Rachel Sanborn, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Providence Health & Services

Authority:

United States: Institutional Review Board

Study ID:

09-97B

NCT ID:

NCT01057212

Start Date:

February 2010

Completion Date:

December 2013

Related Keywords:

  • Non-squamous Non-small Cell Lung Cancer
  • advanced or metastatic non-squamous non-small cell lung cancer (NSCLC)
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

Providence Portland Medical CenterPortland, Oregon  97213-3635