Pazopanib As Pre-Surgical Therapy In Treatment-Naive Subjects With Non-Small Cell Lung Cancer

NCT00367679 | Completed Phase 2 Results

• 1 other identifier: VEG105290
• Study Type: interventional
• Target: 35
• Locations: 3 countries
• Sites: 12

Brief Summary

This is a phase 2 open-label, multicenter, non-randomized study to evaluate the safety and efficacy of oral pazopanib as neoadjuvant treatment for patients with stage 1A, 1B, IIA or IIB (to T2) resectable Non-Small Cell Lung Cancer (NSCLC).

Conditions

Non-Small Cell Lung Cancer; Lung Cancer, Non-Small Cell

Keywords

pazopanib; I-ELCAP; non-small cell lung cancer; antiangiogenesis; NSCLC; GW786034

Outcome Measures

Primary Outcomes (1)

• Number of Participants Achieving Tumor Shrinkage Based on Change in Tumor Volume

  Tumor shrinkage was assessed as the change in tumor volume using high-resolution computed tomography scans of the thorax following treatment with pazopanib. Response is defined as the number of participants achieving at least 50% tumor volume reduction following pazopanib treatment. "Responder" is a participant whose tumor volume reduced at least 50% following pazopanib treatment. "Non-responder" is a participant whose tumor volume did not reduce at least 50% following treatment. Tumor assessments were conducted by a central reviewer.

  Baseline to at least two weeks or at most six weeks

Secondary Outcomes (13)

• Number of Participants Achieving a Clinical Response Based on RECIST

  Baseline to at least two weeks or at most six weeks

• Number of Participants Achieving a >=60% Reduction in Tumor Metabolic Activity Determined as Standard Uptake Value (SUV)

  Baseline to at least two weeks or at most six weeks

• Number of Participants With Shifts From Baseline to Grade 2 or Greater in Hematology Values

  Baseline to at least three weeks and at most 8 weeks

• Number of Participants With Shifts From Baseline to Grade 2 or Greater in Chemistry Values

  Baseline to at least three weeks and at most 8 weeks

• Number of Participants With the Indicated Change From Baseline in Systolic and Diastolic Blood Pressure

  Baseline to at least three weeks and at most 8 weeks

Study Arms (1)

Single Arm

EXPERIMENTAL

800 mg pazopanib oral daily

Drug: Pazopanib

Interventions

Pazopanib DRUG

Pazopanib is an oral, potent, multi-target receptor tyrosine kinase inhibitor of VEGFR-1, -2, -3, PDGFR-alpha and -beta and c-kit. Subjects were to receive 800 mg oral pazopanib daily for a minimum of 2 weeks to a maximum of 6 weeks.

Single Arm

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \[Yankelevitz, 2000, Armato, 2004\]. 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (12)

GSK Investigational Site

Duarte, California, 91010, United States

Location

GSK Investigational Site

Rancho Mirage, California, 92270, United States

Location

GSK Investigational Site

Aurora, Colorado, 80045, United States

Location

GSK Investigational Site

Newark, Delaware, 19718, United States

Location

GSK Investigational Site

Miami, Florida, 33136, United States

Location

GSK Investigational Site

Chicago, Illinois, 60612, United States

Location

GSK Investigational Site

Paramus, New Jersey, 07652, United States

Location

GSK Investigational Site

Flushing, New York, 11355, United States

Location

GSK Investigational Site

New York, New York, 10016, United States

Location

GSK Investigational Site

New York, New York, 10065, United States

Location

GSK Investigational Site

Jerusalem, 91120, Israel

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

Related Publications (4)

• Altorki N, Guarino M, Lee P, et al. Preoperative treatment with pazopanib (GW786034), a multikinase angiogenesis inhibitor in early-stage non-small cell lung cancer (NSCLC): A proof-of-concept phase II study. JCO, 2008 Vol 26, No 15S (May 20 Supplement), 2008: 7557

  BACKGROUND

• Altorki N, Lane ME, Bauer T, Lee PC, Guarino MJ, Pass H, Felip E, Peylan-Ramu N, Gurpide A, Grannis FW, Mitchell JD, Tachdjian S, Swann RS, Huff A, Roychowdhury DF, Reeves A, Ottesen LH, Yankelevitz DF. Phase II proof-of-concept study of pazopanib monotherapy in treatment-naive patients with stage I/II resectable non-small-cell lung cancer. J Clin Oncol. 2010 Jul 1;28(19):3131-7. doi: 10.1200/JCO.2009.23.9749. Epub 2010 Jun 1.

  PMID: 20516450 BACKGROUND

• Altorki N, Heymach J, Guarino M, et al. A Phase II Study of Pazopanib (GW786034) given Preoperatively in Phase I-II Non-Small Cell Lung Cancer (NSCLC): A Proof of Concept Study. Ann Oncol. 2008;19:viii89 [suppl 8; abstr 2250]).

  BACKGROUND

• Nikolinakos PG, Altorki N, Yankelevitz D, Tran HT, Yan S, Rajagopalan D, Bordogna W, Ottesen LH, Heymach JV. Plasma cytokine and angiogenic factor profiling identifies markers associated with tumor shrinkage in early-stage non-small cell lung cancer patients treated with pazopanib. Cancer Res. 2010 Mar 15;70(6):2171-9. doi: 10.1158/0008-5472.CAN-09-2533. Epub 2010 Mar 9.

  PMID: 20215520 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2006
• First Posted: August 23, 2006
• Study Start: November 1, 2006
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: June 12, 2012
• Results First Posted: March 17, 2010

Record last verified: 2012-05

Locations

ES (1); US (10); IL (1)