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Pazopanib As Pre-Surgical Therapy In Treatment-Naive Subjects With Non Small Cell Lung Cancer
This study has been completed.
Sponsored by: GlaxoSmithKline
Information provided by: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00367679
  Purpose

This is a phase 2 open-label, non-randomized study to evaluate the safety and efficacy of pazopanib as pre-surgical treatment for patients with stage 1A or 1B Non Small Cell Lung Cancer (NSCLC).


Condition Intervention Phase
Non-Small-Cell Lung Cancer
Drug: Pazopanib
Phase II

MedlinePlus related topics: Cancer Lung Cancer
Drug Information available for: Pazopanib
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title: A Phase II, Non-Randomized, Multicenter Study to Evaluate the Safety and Efficacy of Pazopanib (GW786034) as Pre-Surgical Therapy in Treatment-Naive Subjects With Stage IA or IB, Resectable Non Small Cell Lung Cancer (NSCLC)

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Evaluate tumor shrinkage based on change in tumor volume using high-resolution CT scans of the thorax and advanced image processing techniques following treatment with pazopanib(2 to 6 weeks) [ Time Frame: 6 Weeks ]

Secondary Outcome Measures:
  • Evaluate change in metabolic activity using PET/CT Determine the objective response rate (complete and partial responses) according to RECIST criteria [ Time Frame: 6 Weeks ]
  • Metabolic response defined as a minimum of 60% decrease in metabolic activity.
  • Safety and tolerability endpoints will consist of the evaluation of AE and changes from screening/baseline in vital signs and clinical laboratory parameters.
  • Response rate defined by the percentage of evaluable subjects who achieved either complete response (CR) or partial response (PR) according to RECIST criteria following treatment with pazopanib.
  • Other Translational Research Endpoints Proportion of cells exhibiting apoptosis in pre-treatment biopsies and post-operative tumor samples.
  • Determine transcriptional profiles from screening/baseline tumor samples. Semiquantitative levels of staining in pre-treatment tumor biopsies (e.g. VEGF, VEGFR-1,VEGFR-2).
  • Presence or absence of amplifications and deletions, and presence, absence, and sequence of mutations in specific genes (such as KRAS, MYC, and TP53) in pre- or post-treatment tumor biopsies.
  • Levels of relevant circulating biomarkers (e.g. sVEGFR-1, sVEGFR-2 or novel candidates determined by proteomic profiling) in the plasma.
  • LDH5 has been shown to be associated with activation of angiogenesis in lung cancer.
  • Circulating levels of LDH5 will be measured at each scheduled visit through Visit 9 to determine if a correlation with drug effect exists. [Koukourakis, 2003; Koukourakis, 2005] Pharmacogenetics (PGx) Research Endpoint
  • Evaluate the presence/absence of genetic variations in select candidate genes in germline DNA.

Estimated Enrollment: 33
Study Start Date: November 2006
Study Completion Date: April 2008
  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Signed, written informed consent provided prior to performing any study-specific procedures or assessments. Subject must be willing to comply with treatment and follow-up.
  • 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, as specified in Section 14.5, Appendix 5 [Yankelevitz, 2000, Armato, 2004]. In addition to the measurable single lesion, other small indeterminate nodules may also be present
  • Disease must consist of only a single lesion and must be measurable according to high-resolution CT scan-assisted volumetric measurement, as specified in Section 14.5, Appendix 5 [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) AST and ALT(≤2.0 X ULN) Renal:Serum creatinine(≤1.5 mg/dL)OR Calculated creatinine clearance(≥30 mL/min)Urine Protein1 (Tace 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 CYP enzymes that metabolize estrogens and progestins (see Section 8.1). 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 (Section 5.2.1).
  • 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 follow:
  • 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

Exclusion criteria:

  • Active malignancy or any malignancy in the 6 months prior to first dose of study drug.
  • 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 excluded.
  • 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 indicated.
  • 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 excluded
  • 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 beginning therapy
  • Active or uncontrolled infection
  • Concurrent treatment with an investigational agent or participation in another clinical trial.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib
  • Has taken/received prohibited medications within the timeframes listed in Section 8.2, Prohibited Medications 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 vein thrombosis).
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00367679

Locations
United States, California
GSK Investigational Site
Duarte, California, United States, 91010
GSK Investigational Site
Rancho Mirage, California, United States, 92270
United States, Colorado
GSK Investigational Site
Aurora, Colorado, United States, 80045
United States, Delaware
GSK Investigational Site
Newark, Delaware, United States, 19718
United States, Florida
GSK Investigational Site
Miami, Florida, United States, 33136
United States, Illinois
GSK Investigational Site
Chicago, Illinois, United States, 60612
United States, New Jersey
GSK Investigational Site
Paramus, New Jersey, United States, 07652
United States, New York
GSK Investigational Site
Flushing, New York, United States, 11355
GSK Investigational Site
New York, New York, United States, 10016
GSK Investigational Site
New York, New York, United States, 10021
Israel
GSK Investigational Site
Jerusalem, Israel, 91120
Spain
GSK Investigational Site
Pamplona, Spain, 31008
GSK Investigational Site
Barcelona, Spain, 08035
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, MD GlaxoSmithKline
  More Information

Responsible Party: GSK ( Study Director )
Study ID Numbers: VEG105290
Study First Received: August 22, 2006
Last Updated: October 27, 2008
ClinicalTrials.gov Identifier: NCT00367679  
Health Authority: United States: Food and Drug Administration;   United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
I-ELCAP
non-small cell lung cancer
NSCLC
pazopanib
GW786034
antiangiogenesis

Study placed in the following topic categories:
Thoracic Neoplasms
Non-small cell lung cancer
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:
Respiratory Tract Neoplasms
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on January 16, 2009