Know Cancer

forgot password

A Multicenter, Open-Label, Randomized, Phase II Trial of Docetaxel, Carboplatin and Bevacizumab as First-Line Treatment, Followed by Bevacizumab Plus Pemetrexed Versus Pemetrexed Alone as Second-Line Treatment of Stage IIIB or IV Non-Small Cell Lung Cancer

Phase 2
18 Years
Open (Enrolling)
Stage IIIB or IV Non-Small Cell Lung Cancer

Thank you

Trial Information

A Multicenter, Open-Label, Randomized, Phase II Trial of Docetaxel, Carboplatin and Bevacizumab as First-Line Treatment, Followed by Bevacizumab Plus Pemetrexed Versus Pemetrexed Alone as Second-Line Treatment of Stage IIIB or IV Non-Small Cell Lung Cancer

This phase II clinical trial will address the issues of bevacizumab treatment duration and
treatment safety as first-line therapy for patients with non-squamous NSCLC. Following
disease progression or treatment failure, the potential benefit of continued bevacizumab
therapy will be tested by randomizing patients to two treatment arms, including second-line
chemotherapy with or without further bevacizumab. It is hypothesized that continuation of
bevacizumab with pemetrexed as second-line treatment following progression will result in
improved clinical outcomes for patients with NSCLC.

Inclusion Criteria:

- Age ≥ 18 years

- Histologically or cytologically confirmed stage IIIB with malignant pleural
effusion or stage IV NSCLC except squamous-cell carcinoma

- Measurable disease defined by RECIST

- Adequate organ function:

1. Absolute neutrophil count ≥ 1.5 x 10(9)/L

2. Hemoglobin ≥ 9.0 g/dL

3. Platelets ≥ 100 x 10(9)/L

4. Hepatic enzyme levels: AST and ALT and Alkaline Phosphatase must be within
range allowing for eligibility. In determining eligibility, the more abnormal of
the two values (AST or ALT) should be used according to table listed in the

5. Bilirubin ≤ ULN

6. Serum Creatinine ≤ 1.5 mg/dL (or creatinine clearance ≥ 60mL/min)

7. Urine protein/creatinine ratio < 1.0 OR urine dipstick for proteinuria < 2 +
(patients discovered to have ≥ 2 + proteinuria on dipstick urinalysis at
baseline should undergo a 24 hour urine collection and must demonstrate ≤1g of
protein in 24 hours to be eligible)

8. INR ≤ 1.5

9. PTT ≤ ULN

- ECOG Performance Status 0-1

- Estimated survival of ≥ 12 weeks

- Provide written informed consent

Exclusion Criteria:

- Prior chemotherapy for advanced NSCLC

- Neoadjuvant or adjuvant treatment within six (6) months of registration

- Prior radiation therapy within three (3) weeks of registration; all side effects must
have resolved by registration

- Prior treatment with an investigational or marketed agent that acts by
antiangiogenesis mechanisms

- Large ( > 4 cm) centrally located lesions or large lesions in close proximity to
major blood vessels unless treated with palliative radiation

- Brain metastases or leptomeningeal disease, except for patients who have had a
resection and/or completed a course of cranial irradiation, have no worsening CNS
symptoms, and have discontinued all corticosteroids for that indication for at least
one (1) month prior to registration

- History of gross hemoptysis (defined as bright red blood of at least ½ teaspoon or
2.5 mL per episode) within three (3) months of registration unless definitively
treated with surgery, radiation, arteriographic embolization, or endobronchial
interventions at least four (4) weeks prior to registration

- Presence of cavitory lesion

- Presence of squamous 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)

- Peripheral neuropathy > grade 1

- Major surgery, open biopsy or significant traumatic injury within four (4) weeks of
registration or anticipation of need for major surgical procedure during the course
of the study

- Minor surgical procedures, fine needle aspirations or core biopsies within one (1)
week prior to registration

- Current, ongoing therapeutic anticoagulation with full-dose warfarin or its

- Current or recent (within ten [10] days of the first dose of study treatment) use of
aspirin (at least 325 mg/day) or other NSAIDs with anti-platelet activity or
treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix),
or cilostazol (Pletal)

- History of prior malignancy within the past three (3) years except for curatively
treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or
treated localized prostate cancer with a current PSA of < 1.0 mg/dL on two successive
evaluations, at least three (3) months apart, with the most recent evaluation no more
than four (4) weeks prior to registration

- History of serious systemic disease including:

1. Unstable angina, New York Heart Association (NYHA) ≥ Grade II or congestive
heart failure

2. Inadequately controlled hypertension (blood pressure >150/100 mmHg while taking
antihypertensive medications)

3. Unstable symptomatic arrhythmia requiring medication

4. Myocardial infarction within six (6) months prior to registration

5. Stroke within six (6) months prior to registration

6. Transient ischemic attack within six (6) months prior to registration

7. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
within six (6) months prior to registration

8. Clinically significant peripheral vascular disease or evidence of bleeding,
diathesis (prone to bleeding) or coagulopathy

9. Active systemic bacterial, fungal or viral infection, including known HCV and

- Pregnancy or women who are breast-feeding; women of child-bearing potential and
non-vasectomized men must agree to use effective methods of birth control during and
three (3) months following treatment period and women of child-bearing potential must
have a negative pregnancy test

- History of severe hypersensitivity reaction to docetaxel or any other drugs
formulated with polysorbate 80

- Any other medical condition, including mental illness or substance abuse, which in
the judgment of the investigator, is likely to interfere with a patient's ability to
provide informed consent, cooperate, and participate in the study, or to interfere
with the interpretation of the results

- Use of any investigational agent within four (4) weeks prior to registration

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS) of bevacizumab and pemetrexed compared to pemetrexed monotherapy during second-line treatment of Stage IIIB or IV NSCLC

Outcome Time Frame:

Duration of study

Safety Issue:


Principal Investigator

Chandra P Belani, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Penn State Milton S. Hershey Medical Center, Penn State College of Medicine, Penn State Hershey Cancer Institute


United States: Institutional Review Board

Study ID:

PSHCI 08-009



Start Date:

October 2008

Completion Date:

August 2013

Related Keywords:

  • Stage IIIB or IV Non-Small Cell Lung Cancer
  • Non-Small Cell Lung Cancer
  • Advanced Non-Small Cell Lung Cancer
  • Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms