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Pazopanib Hydrochloride or a Placebo in Treating Patients With Non-Small Cell Lung Cancer Who Have Received First-Line Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01208064
Recruitment Status : Terminated (based on IDMC decision)
First Posted : September 23, 2010
Last Update Posted : July 12, 2018
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Tracking Information
First Submitted Date  ICMJE September 22, 2010
First Posted Date  ICMJE September 23, 2010
Last Update Posted Date July 12, 2018
Study Start Date  ICMJE July 2011
Actual Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 22, 2010)
Overall survival
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 22, 2010)
  • Progression-free survival (PFS) overall and at 6 and 12 months
  • Toxicity
  • Correlation of C-reactive protein with PFS at weeks 6, 14, and 22
  • Quality of life
  • Comparison of discontinuation rate with treatment compliance
  • Health economics
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pazopanib Hydrochloride or a Placebo in Treating Patients With Non-Small Cell Lung Cancer Who Have Received First-Line Chemotherapy
Official Title  ICMJE Double Blind Randomized Phase III Study of Maintenance Pazopanib Versus Placebo in NSCLC Patients Non Progressive After First Line Chemotherapy. MAPPING, an EORTC Lung Group Study.
Brief Summary

RATIONALE: Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether pazopanib hydrochloride is more effective than a placebo in treating patients with non-small cell lung cancer that has not progressed after first-line chemotherapy.

PURPOSE: This randomized phase II/III trial is studying how well giving pazopanib hydrochloride works and compares it with giving a placebo in treating patients with non-small cell lung cancer who have received first-line chemotherapy.

Detailed Description

OBJECTIVES:

Primary

  • To compare the therapeutic benefit, in terms of overall survival, of maintenance pazopanib hydrochloride in patients with non-small cell lung cancer who have not progressed after first-line chemotherapy.

Secondary

  • To compare progression-free survival (PFS) overall and at specific time points (6 and 12 months).
  • To document the toxicity profile of pazopanib hydrochloride according to the CTCAE v 4.
  • To assess the use of C-reactive protein (CRP) in the detection of progression of disease in the maintenance phase of therapy.
  • To compare quality-of-life of patients on maintenance therapy.
  • To compare discontinuation rate/treatment compliance of patients treated with these regimens.
  • To collect health economics data on resource utilization as documented by the EQ-5D generic QoL instrument.

Tertiary (correlative)

  • To evaluate the effect of germline genetic variations on drug response (pharmacogenetics) using PAX gene.
  • To find relevant biomarkers of VEGFR pathways from plasma samples.
  • To obtain the pharmacokinetics of pazopanib hydrochloride at 600 and 800 mg.
  • To evaluate biomarkers in tumor tissue.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to center, histology (squamous vs nonsquamous), performance status (0-1 vs 2 up to 15% of patients), and response to initial chemotherapy (complete response/partial response vs stable disease). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive an oral placebo daily on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive oral pazopanib hydrochloride daily on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients complete quality-of life-questionnaires (QLQ-C30 and QLQ-LC13) at baseline, 6 weeks, 14 weeks, and 22 weeks.

Health economics data on resource utilization are collected and documented using the EQ-5D questionnaire.

Blood samples may be collected periodically for pharmacokinetics and pharmacogenetic studies. Samples are analyzed for germline genetic variations on drug response, relevant biomarkers of VEGFR pathways, and concentration of pazopanib hydrochloride. Previously collected tumor tissue is analyzed for biomarkers.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Lung Cancer
Intervention  ICMJE
  • Drug: pazopanib hydrochloride
  • Other: laboratory biomarker analysis
  • Other: pharmacogenomic studies
  • Other: pharmacological study
  • Procedure: quality-of-life assessment
Study Arms  ICMJE
  • Experimental: Pazopanib
    2 weeks at 600mg and then maintenance at 800mg
    Interventions:
    • Drug: pazopanib hydrochloride
    • Other: laboratory biomarker analysis
    • Other: pharmacogenomic studies
    • Other: pharmacological study
    • Procedure: quality-of-life assessment
  • Placebo Comparator: Placebo
    placebo match 2 weeks at 600mg and then maintenance at 800mg
    Interventions:
    • Other: laboratory biomarker analysis
    • Other: pharmacogenomic studies
    • Other: pharmacological study
    • Procedure: quality-of-life assessment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 3, 2014)
102
Original Estimated Enrollment  ICMJE
 (submitted: September 22, 2010)
600
Actual Study Completion Date  ICMJE June 2015
Actual Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) meeting the following criteria:

    • Any histology
    • Stage IIIB-IV disease
  • Newly diagnosed or recurrent disease (after surgery or radical radiotherapy) proven on cytology or histology before induction chemotherapy

    • In case of adjuvant chemotherapy after previous surgery, time interval from start of previous treatment to induction chemotherapy for metastatic disease is 12 months
  • May or may not have measurable disease as defined by RECIST criteria
  • Must not have progressed during the 4 courses of initial chemotherapy

    • For patient presenting with measurable disease, there must be documented radiographic evidence of response (complete response, partial response, or stable disease) according to RECIST 1.1 criteria
    • For patients without measurable disease, there must be no symptomatic/clinical progression
  • EGFR wild-type or unknown (known EGFR mutations are not eligible)
  • Brain metastases allowed provided they are controlled and the patient must present with a performance status (PS) of 0-1 after the 4 courses of chemotherapy and at least 1 week off steroids
  • No known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage, including any of the following:

    • Large protruding endobronchial lesions in the main or lobar bronchi

      • Endobronchial lesions in the segmented bronchi are allowed
    • Lesions extensively infiltrating the main or lobar bronchi

      • Minor infiltrations in the wall of the bronchi are allowed
    • Lesions infiltrating major pulmonary vessels (contiguous tumor and vessels)

      • Tumors touching but not infiltrating (abutting) the vessels are acceptable

PATIENT CHARACTERISTICS:

  • WHO performance status (PS) 0-2

    • PS 2 capped at 15% of the study population
    • Elderly population (i.e., > 70 years old) capped at 15% and must be PS 0-1
  • Life expectancy ≥ 12 weeks
  • ANC ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Hemoglobin ≥ 9 g/dL
  • PT or INR ≤ 1.2 times upper limit of normal (ULN)
  • PTT ≤ 1.2 times ULN
  • Bilirubin ≤ 1.5 times ULN
  • AST/ALT ≤ 2.5 times ULN
  • Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min
  • Urine protein:creatinine ratio ≤ 1 OR ≤ 1.0 g of protein by 24-hour urine collection
  • May only be randomized in this trial once
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception 2 weeks prior to, during, and for at least 1 month after completion of study therapy
  • Corrected QT interval (QTc) ≤ 480 msec on normal 12-lead ECG

    • If QTc interval is > 480 msec, then 2 additional ECGs should be obtained over a brief period of time (e.g., within 15-20 minutes) to confirm the abnormality and the average QTc interval will be determined from the 3 ECG tracings by manual evaluation and will be used to determine if the patient will be excluded from the study
  • No history of any of the following cardiovascular conditions within the past 6 months:

    • Cardiac angioplasty or stenting myocardial infarction
    • Unstable angina
    • Coronary artery bypass graft surgery
    • Symptomatic peripheral vascular disease
  • No NYHA class III-IV congestive heart failure (no class II, III, or IV for elderly patients)
  • LVEF normal
  • No other malignancy within the past 2 years except for non-small cell lung cancer
  • No poorly controlled hypertension, defined as blood pressure (BP) > 140/90 mm Hg

    • Initiation or adjustment of antihypertensive medications is permitted prior to study entry provided blood pressure is reassessed on two occasions that are separated by a minimum of 1 hour and the mean systolic BP/diastolic BP values must be ≤ 140/90 mm Hg
  • No cerebrovascular accident (at any time in the past), transient ischemic attack, deep venous thrombosis (DVT), or pulmonary embolism within the past 6 months

    • Patients with recent DVT who have been treated with therapeutic anticoagulating agents and remained stable for at least 6 weeks are eligible
  • No hemoptysis within the past 6 weeks (patients with a history of hemoptysis associated with metastatic disease must undergo a bronchoscopy to rule out endobronchial lesions and patients with an endobronchial lesion will be excluded from the study)
  • No history of clinically significant gastrointestinal disorders, including any of the following:

    • Malabsorption syndrome
    • Major resection of the stomach or small bowel that could affect the absorption of the study drug
    • Active peptic ulcer disease
    • Known intraluminal metastatic lesions with risk of bleeding
    • Inflammatory bowel disease
    • Ulcerative colitis
    • Other gastrointestinal conditions with increased risk of perforation
  • No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No evidence of active bleeding or bleeding diathesis
  • No trauma within the past 28 days
  • No nonhealing wound, fracture, or ulcer
  • No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib hydrochloride
  • No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No ongoing toxicity from prior anticancer therapy that is > grade 1 (except alopecia) and/or that is progressing in severity
  • At least 6 months since prior amiodarone
  • At least 14 days since prior CYP3A4 substrates
  • At least 2 weeks since prior palliative radiotherapy
  • No major surgery within the past 28 days
  • No prior multi-target tyrosine kinase inhibitor (TKI), bevacizumab, or cetuximab (as part of induction therapy)
  • Prior radical radiotherapy allowed provided it was at least 12 months from start of induction chemotherapy for metastatic disease
  • Concurrent anticoagulant therapy allowed provided the patient's PT, INR, or PTT is stable and within the recommended range for the desired level of anticoagulation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Egypt,   France,   Germany,   Greece,   Netherlands,   Slovenia,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01208064
Other Study ID Numbers  ICMJE EORTC-08092
2010-018566-23 ( EudraCT Number )
EU-21072
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party European Organisation for Research and Treatment of Cancer - EORTC
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE European Organisation for Research and Treatment of Cancer - EORTC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mary O'Brien, MD Royal Marsden NHS Foundation Trust
PRS Account European Organisation for Research and Treatment of Cancer - EORTC
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP