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Phase II Clinical Study of Weekly Topotecan in Combination With Avastin™ in Patients With Stage IIIB/IV Non-Small Cell Lung Cancer Who Have Failed Prior Systemic Chemotherapy

Phase 2
18 Years
Not Enrolling
Lung Cancer

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Trial Information

Phase II Clinical Study of Weekly Topotecan in Combination With Avastin™ in Patients With Stage IIIB/IV Non-Small Cell Lung Cancer Who Have Failed Prior Systemic Chemotherapy



- Determine the progression-free survival of patients with stage IIIB or IV non-small
cell lung cancer treated with topotecan hydrochloride and bevacizumab who have failed
prior systemic chemotherapy.


- Determine the objective response rates in patients treated with this regimen.

- Measure time-to-event efficacy variables, including time to objective tumor response
(for responding patients), duration of response (for responding patients), time to
treatment failure, and overall survival.

- Characterize the quantitative and qualitative toxicities of this regimen in these

OUTLINE: Patients receive topotecan hydrochloride intravenously (IV) over 30 minutes on days
1, 8, and 15 and Avastin (bevacizumab) IV over 30-90 minutes on days 1 and 15. Treatment
repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 6 months from

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed non-small cell lung
cancer (NSCLC). Patients with extrathoracic-only squamous cell NSCLC are eligible.
Intrathoracic squamous cell carcinoma will not be eligible. Mixed tumors will be
categorized by the predominant cell type unless small cell elements are present, in
which case the patient is ineligible.

- Disease that has failed one or more prior standard therapy and is no longer likely to
respond to such therapy.

- Prior systemic chemotherapy, immunotherapy, or biological therapy is allowed, except
for prior use of Avastin and topotecan in combination. Patient must be at least 14
days from previous radiation or systemic therapy (at least 30 days for
investigational agents) and have recovered from the acute toxic effects of the
treatment prior to study enrollment.

- Disease status must be measurable or evaluable as defined by Response Evaluation
Criteria In Solid Tumors (RECIST criteria)

- Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1

- Age 18 years or greater

- Adequate organ function within 14 days of study registration including the following:

- Adequate bone marrow reserve:

- absolute neutrophil count (ANC) > or = to 1.5 x 10^9/L,

- platelets >100 x 10^9/L,

- hemoglobin > 9 g/dL

- Hepatic:

- bilirubin <1.5 times the upper limit of normal (x ULN),

- alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine
transaminase (ALT) <3.0 x ULN (ALP, AST, and ALT <5 x ULN is acceptable if
liver has tumor involvement)

- Renal:

- serum creatinine < 2.0

- 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

- Coagulation:

- International Normalized Ratio (INR) < 1.5

- Partial thromboplastin time (PTT) < the upper limits of normal (ULN)

- Women of childbearing potential and sexually active males are required to use an
effective method of contraception (ie, a hormonal contraceptive, intra-uterine
device, diaphragm with spermicide, condom with spermicide, or abstinence) during the
study and for 3 months after the last dose of study drug.

- Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

- Pregnant (positive pregnancy test) or breast-feeding. Topotecan is pregnancy
category D - clear evidence of risk in pregnancy; Avastin is pregnancy category C -
risk in pregnancy cannot be ruled out. Pregnancy testing is not required for
post-menopausal or surgically sterilized women

- Known hypersensitivity to any component of Avastin (bevacizumab)

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

- 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

- Known central nervous system (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, 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

- Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
recent peripheral arterial thrombosis) within 6 months prior to Day 1

- History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 month
prior to Day 1

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

- Active malignancy other than non-small cell lung cancer (NSCLC), treated superficial
basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix
within last five years are allowed.

- 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

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to Day 1

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

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

Type of Study:


Study Design:

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

Outcome Measure:

Median Time to Disease Progression

Outcome Description:

Assessed by Response Evaluation Criteria In Solid Tumor (RECIST criteria). Progression is defined as a measureable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions since baseline.

Outcome Time Frame:

From Day 1 Until First Documented Disease Progression or Date of Death (Whichever Occurred First)

Safety Issue:


Principal Investigator

Arkadiusz Dudek, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota


United States: Food and Drug Administration

Study ID:




Start Date:

September 2006

Completion Date:

September 2011

Related Keywords:

  • Lung Cancer
  • recurrent non-small cell lung cancer
  • stage IIIB non-small cell lung cancer
  • stage IV non-small cell lung cancer
  • adenocarcinoma of the lung
  • bronchoalveolar cell lung cancer
  • large cell lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Park Nicollet Cancer Center St. Louis Park, Minnesota  55416
Masonic Cancer Center at University of Minnesota Minneapolis, Minnesota  55455