A Phase II Open-Label Multicenter Study to Evaluate the Safety and Efficacy of Pazopanib (GW786034) as Neoadjuvant Therapy in Treatment-Naïve Subjects With Stage IA, IB, IIA or IIB (to T2) Resectable Non-Small Cell Lung Cancer (NSCLC)
- Signed, written informed consent provided prior to performing any study-specific
procedures or assessments. Subject must be willing to comply with treatment and
- Subjects ≥21 years of age with a life expectancy of ≥12 weeks
- The time between initial diagnosis and the scheduled surgery date allows for the
subject to receive a minimum of 2 weeks or a maximum of 6 weeks treatment with
pazopanib. Note: At least 4 weeks must be available between the diagnostic biopsy
and surgery to allow for 1) one-week delay following the diagnostic biopsy prior to
first dose of study drug, 2) minimum of 2 weeks on study drug, and 3) minimum of 1
week wash out prior to surgery.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
- Histologically- or cytologically-confirmed Stage IA, IB, IIA, or IIB (to T2) NSCLC
according to the International Staging System [Mountain, 1997] and must be scheduled
for surgical resection.
- Disease must consist of only a single lesion and must be measurable according to
high-resolution CT scan-assisted volumetric measurement [Yankelevitz, 2000, Armato,
2004]. In addition to the measurable single lesion, other small indeterminate
nodules may also be present
- No approved or investigational anti-cancer therapy concurrently or in the 6 months
prior to start of study drug, including surgery, tumor embolization, chemotherapy,
radiation therapy, immunotherapy, hormone therapy, biologic therapy, or
anti‑angiogegneic therapy (e.g., inhibitors of VEGF or VEGFR).
- Fresh tumor biopsy for apoptosis and relevant biomarker analyses must be obtained
within 30 to 8 days of first dose of study drug and must be available for all
subjects prior to start of pazopanib treatment.
- System (Laboratory Values)
- Hematologic:Absolute neutrophil count (ANC)(≥ 1.5 X 109/L), Hemoglobin (≥9 g/dL),
Platelets(≥100 X 109/L)
- Hepatic:Albumin (≥ 2.5 g/dL), Serum bilirubin(≤1.5 X upper limit of normal (ULN)
unless due to Gilbert's syndrome), aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) (≤2.0 X ULN) Renal:Serum creatinine(≤1.5 mg/dL) OR Calculated
creatinine clearance (≥30 mL/min), Urine Protein (Trace or +1 by dipstick urinalysis
or <1.0 gram determined by 24-hour urine protein analysis.)
- Ability to swallow and retain oral medication
- A female is eligible to enter and participate in this study if she is of:
- Non-childbearing potential (i.e., physiologically incapable of becoming pregnant),
including any female who has had:
- A hysterectomy
- A bilateral oophorectomy (ovariectomy)
- A bilateral tubal ligation
- Is post-menopausal:
- Subjects not using hormone replacement therapy (HRT) must have experienced total
cessation of menses for ≥1 year and be greater than 45 years in age, OR, in
questionable cases, have a follicle stimulating hormone (FSH) value >40mIU/mL and an
estradiol value <40pg/mL (<140pmol/L).
- Subjects must discontinue HRT prior to study enrollment due to the potential for
inhibition of cytochrome P450 enzymes that metabolize estrogens and progestins. For
most forms of HRT, at least 2‑4 weeks must elapse between the cessation of HRT and
determination of menopausal status; length of this interval depends on the type and
dosage of HRT. If a female subject is determined not to be post-menopausal, they
must use adequate contraception, as defined immediately below.
- Childbearing potential, including any female who has had a negative serum pregnancy
test within 2 weeks prior to the first dose of study treatment, preferably as close
to the first dose as possible, and agrees to use adequate contraception.
GlaxoSmithKline (GSK)-acceptable contraceptive methods, when used consistently and in
accordance with both the product label and the instructions of the physician, are as
- An intrauterine device with a documented failure rate of less than 1% per year
- Vasectomized partner who is sterile prior to the female subject's entry and is the
sole sexual partner for that female
- Complete abstinence from sexual intercourse for 14 days before exposure to
investigational product, through the dosing period, and for at least 21 days after
the last dose of investigational product
- Double-barrier contraception (condom with spermicidal jelly, foam suppository, or
film; diaphragm with spermicide; or male condom and diaphragm with spermicide) Note:
Oral contraceptives are not reliable due to potential drug‑drug interactions.
- Female subjects who are lactating should discontinue nursing prior to the first dose
of study drug and should refrain from nursing throughout the treatment period and for
15 days following the last dose of study drug.
- A male with a female partner of childbearing potential is eligible to enter and
participate in the study if he uses a barrier method of contraception or abstinence
during the study.
- Subjects must complete all screening assessments as outlined in the protocol
- Active malignancy or any malignancy in the 6 months prior to first dose of study
- Concurrent disease or condition that would make the subject inappropriate for study
participation including (1) any unresolved or unstable, serious toxicity from prior
administration of another investigational drug, (2) any serious medical disorder that
would interfere with the subject's safety, obtaining informed consent, or compliance
with all study related procedures.
- Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks
prior to beginning therapy, or anticipation of the need for a major surgical
procedure during the course of the study; minor surgical procedures such as fine
needle aspiration or core biopsy within 1 week prior to beginning therapy are also
- History or clinical evidence of central nervous system (CNS) metastases or
leptomeningeal carcinomatosis. Routine screening with CNS imaging studies (computed
tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically
- History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
- History of hemoptysis
- Malabsorption Syndrome, disease significantly affecting gastrointestinal function, or
resection of the stomach or small bowel. Subjects with ulcerative colitis are also
- Active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal
condition increasing the risk of perforation; history of abdominal fistula,
gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to
- Active or uncontrolled infection
- Concurrent treatment with an investigational agent or participation in another
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to pazopanib
- Has taken/received prohibited medications within specified timeframes.
- Corrected QT interval (QTc) prolongation defined as QTc interval >480 msecs
- History of any one of the following cardiac conditions within the past 6 months:
cardia angioplasty or stenting, myocardial infarction,or unstable angina
- History of cerebrovascular accident within the past 6 months
- Has Class II, III or IV heart failure as defined by the New York Heart Association
(NYHA) functional classification system.
- Poorly controlled hypertension (mean systolic blood pressure (SBP) of ≥140mmHg, or
mean diastolic blood pressure (DBP) of ≥ 90mmHg. Note: Initiation or adjustment of
anti-hypertensive medication(s) is permitted prior to study entry. The blood pressure
(BP) must be re-assessed on two occasions that are separated by a minimum of 5
minutes. The mean SBP/DBP values from both BP assessments must be < 140/90mmHg in
order for a subject to be eligible for the study.
- History of untreated deep venous thrombosis (DVT) within the past 6 months (e.g. calf
- Presence of any non-healing wound, fracture, or ulcer, or the presence of symptomatic
peripheral vascular disease.
- Receiving therapeutic warfarin or heparin as a concurrent medication. Note:
prophylactic low-dose warfarin (less than or equal to 2 mg daily) is permitted.
- Evidence of bleeding diathesis or coagulopathy
- Pregnant or lactating female