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Non-Small Cell Lung CancerPhase 2NCT00367679

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

A Phase 2 study testing Pazopanib in people with Non-Small Cell Lung Cancer and Lung Cancer, Non-Small Cell, run by GlaxoSmithKline at 12 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 21 years and older
What is being tested?
Pazopanib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
12 sitesin 3 countries
Study dates
Nov 2006to Apr 2008
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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 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

Who cannot join

  • 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
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  • 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
  • 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

Trial locations and contacts

12 sites in 3 countries.

12 sites in 3 countries

United States10 sites

  • GSK Investigational Site

    Aurora, Colorado, 80045

  • GSK Investigational Site

    Chicago, Illinois, 60612

  • GSK Investigational Site

    Duarte, California, 91010

  • GSK Investigational Site

    Flushing, New York, 11355

  • GSK Investigational Site

    Miami, Florida, 33136

  • GSK Investigational Site

    New York, New York, 10016

  • GSK Investigational Site

    New York, New York, 10065

  • GSK Investigational Site

    Newark, Delaware, 19718

  • GSK Investigational Site

    Paramus, New Jersey, 07652

  • GSK Investigational Site

    Rancho Mirage, California, 92270

Other trials in United States

Israel1 site

  • GSK Investigational Site

    Jerusalem, 91120

Other trials in Israel

Spain1 site

  • GSK Investigational Site

    Barcelona, 08035

Other trials in Spain

About this study

Official title: 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)

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).

Being tested
Pazopanib
Keywords
pazopanib, I-ELCAP, non-small cell lung cancer, antiangiogenesis, NSCLC, GW786034
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PazopanibDrug

    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.

Study groups in NCT00367679
Study groupRoleWhat they receive
Single ArmExperimental800 mg pazopanib oral daily
Receives: Drug: Pazopanib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to at least two weeks or at most six weeks

Secondary outcomes (13)

  1. Number of Participants Achieving a Clinical Response Based on RECIST

    Response is the number of participants achieving either complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR, all detectable tumor has disappeared; PR, a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum; Progressive disease (PD), a >=20% increase in target lesions; Stable Disease, small changes not meeting previously given criteria. Confirmation requires at least 2 assessments (conducted by a central reviewer) of CR/PR with at least 4 weeks between the assessments.

    Measured: Baseline to at least two weeks or at most six weeks

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

    Response is the number of participants whose tumor demonstrated a 60% or greater reduction in metabolic activity (SUV) as measured by positron emission tomography (PET) or PET/computed tomography (PET/CT) at the end of treatment visit relative to baseline. This analysis was not conducted because insufficient data were collected: only three participants had PET/CT data.

    Measured: Baseline to at least two weeks or at most six weeks

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

    Shifts in hematology values by grade were summarized based on the National Institutes of Health (NIH) Common Terminology Criteria for Adverse Events (Version 3.0 - definitions provided with each parameter below). Shifts to Grade 2 or greater at any point in the study following baseline are reported here.

    Measured: Baseline to at least three weeks and at most 8 weeks

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

    Shifts in chemistry values by grade were summarized based on the NIH Common Terminology Criteria for Adverse Events (Version 3.0 - definitions provided with each parameter below). Shifts to Grade 2 or greater at any point in the study following baseline are reported here. ULN = upper limit of normal; Gr = grade; mg = milligrams; dL = deciliter; mmol = millimoles.

    Measured: Baseline to at least three weeks and at most 8 weeks

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

    Increases in systolic or diastolic blood pressure values at any point in the study following baseline were summarized. mmHg = millimeters of mercury. Baseline blood pressure values as well as the change from baseline experienced are given in the category titles.

    Measured: Baseline to at least three weeks and at most 8 weeks

  6. Number of Cells Exhibiting Apoptosis in Participant Samples

    Tumor cells from pre-treatment and post-operative biopsies were to have been analyzed to determine the number of cells that were exhibiting apoptosis. Due to the limited quantity of tissue in pre- and post-treatment biopsy samples, these assays were not performed.

    Measured: Baseline to at least three weeks and at most 8 weeks (surgery date)

  7. Ratio of Post- to Pretreatment Expression Levels for Each of the Indicated Pazopanib Target Genes

    Gene expression data analysis was performed with GeneSpring GX 7.3.1 (Agilent Technologies). Data were preprocessed using the RMA algorithm. The Benjamini and Hochberg false discovery rate was used for multiple testing corrections. Data below are log-transformed ratios of the post-treatment to pre-treatment expression intensity, indicating the fold increase/decrease in expression of genes. PDGF, platelet-derived growth factor; VEGFR, vascular endothelial growth factor receptor; c-KIT, a protein tyrosine kinase that is a receptor for stem cell factor or "kit" ligand.

    Measured: Baseline to at least three weeks and at most 8 weeks (surgery date)

  8. Gene Mutations in Pre- or Post-treatment Tumor Biopsies

    Specific genes (KRAS, MYC, TP53, and others) were to have been analyzed for the presence or absence of amplifications or deletions and for the presence, absence, and sequence of point mutations in pre- or post-treatment tumor biopsies. These analyses were not conducted because the potential results were considered to provide overlapping information with those obtained in the transcriptional and proteomic profiling assays that were conducted. The clinical study report indicates that genetic measures were to have been reported separately.

    Measured: Baseline to at least three weeks and at most 8 weeks (surgery date)

  9. Intratumoral Levels of Specific Biomarkers

    A pre-treatment tumor biopsy from each participant was to have been analyzed by Western blotting to semi-quantitate levels of various proteins related to angiogenesis and/or to the mechanism of action of pazopanib. These assays were not carried out due to insufficient quantity of tissue present in the pre-treatment biopsy (fine needle aspirate). The clinical study report indicates that results were to have been reported separately.

    Measured: Baseline tumor biopsy

  10. Plasma Levels of Lactate Dehydrogenase-5 (LDH5)

    LDH5 has been shown to be associated with activation of angiogenesis in lung cancer. Circulating levels of LDH5 were to have been measured at each scheduled visit through the post-treatment visit to determine if a correlation with drug effect existed. Levels of LDH5 were measured, but the team determined that greater value was to be derived from transcriptional and plasma biomarker analyses; thus, no analyses were conducted to examine the correlation of LDH5 levels with effects of pazopanib.

    Measured: Baseline to at least three weeks and at most 8 weeks

  11. Genetic Variations in Germline DNA

    Plasma samples were collected from each consenting participant, generally at baseline, to permit evaluation of the presence or absence of genetic variations in select candidate genes in germline DNA. Analyses that could have been done might have examined the relationship between genetic variants and the safety or tolerability or the efficacy of pazopanib. Analyses have not yet been conducted, but a need to do so may yet be identified. The clinical study report indicated that results, if any, would be reported separately.

    Measured: Baseline

  12. Semiquantitative Levels of Staining in Pre-treatment Tumor Biopsies (e.g. VEGF, VEGFR-1,VEGFR-2).

    Analysis not performed as part of study. Appropriate material was not available for analysis.

    Measured: Entire study interval

  13. Ratio of Post- to Pretreatment Expression Levels for Each of the Indicated Pazopanib Target Proteins

    Baseline and post-therapy plasma samples were obtained from participants. Immunohistochemistry analyses were carried out using a BioPlex 200 machine (Bio-Rad) or by enzyme-linked immunoassays to evaluate levels of angiogenesis-related proteins and other relevant proteins. Post- and pre-treatment changes in cytokines and angiogenic factors in response to pazopanib were analyzed. A negative value indicates that the post-treatment level of the particular target protein was less than the pre-treatment level.

    Measured: Baseline to at least two weeks and at most 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Aug 2006 (estimated)
  2. Study startNov 2006
  3. Primary completionApr 2008
  4. Study completionApr 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00367679
Sponsor's protocol ID
VEG105290
Status last verified
May 2012
First submitted
22 Aug 2006
Last updated
12 Jun 2012
Data monitoring committee
No

Publications

  • 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

  • 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.

    PubMed 20516450

  • 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]).

  • 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.

    PubMed 20215520

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pazopanib in people with Non-Small Cell Lung Cancer and Lung Cancer, Non-Small Cell, run by GlaxoSmithKline at 12 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States, Israel, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Mar 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Achieving Tumor Shrinkage Based on Change in Tumor Volume (time frame: Baseline to at least two weeks or at most six weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00367679, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2012.

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