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

This study has been terminated.
(based on IDMC decision)
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT01208064
First received: September 22, 2010
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Drug: pazopanib hydrochloride
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Other: pharmacological study
Procedure: quality-of-life assessment
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival (PFS) overall and at 6 and 12 months [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Correlation of C-reactive protein with PFS at weeks 6, 14, and 22 [ Designated as safety issue: No ]
  • Quality of life [ Designated as safety issue: No ]
  • Comparison of discontinuation rate with treatment compliance [ Designated as safety issue: No ]
  • Health economics [ Designated as safety issue: No ]

Enrollment: 102
Study Start Date: July 2011
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pazopanib
2 weeks at 600mg and then maintenance at 800mg
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
Other: laboratory biomarker analysis Other: pharmacogenomic studies Other: pharmacological study Procedure: quality-of-life assessment

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01208064

Locations
Belgium
Universitair Ziekenhuis Gent
Gent, Belgium
Centre Hospitalier Regional De La Citadelle
Liege, Belgium
Clinique et Maternité Sainte Elisabeth
Namur, Belgium
Egypt
National Cancer Institute
Cairo, Egypt
France
Centre Georges-Francois-Leclerc
Dijon, France
Assistance Publique - Hôpitaux de Marseille - Assistance Publique - Hôpitaux de Marseille - Hopital Nord
Marseille, France
Germany
Klinik Loewenstein
Loewenstein, Germany
UniversitaetsMedizin Mannheim
Mannheim, Germany
Greece
University General Hospital Heraklion
Heraklion, Greece
Netherlands
The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
Amsterdam, Netherlands
Amphia Ziekenhuis
Breda, Netherlands
Isala Klinieken
Zwolle, Netherlands
Slovenia
University Clinic Golnik
Golnik, Slovenia
United Kingdom
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT
Western General Hospital
Edinburgh, United Kingdom
Royal Marsden Hospital
London, United Kingdom
Guy's and St Thomas' NHS
London, United Kingdom
Christie NHS Foundation Trust
Manchester, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom
Weston Park Hospital
Sheffield, United Kingdom
Royal Marsden Hospital
Sutton, United Kingdom
King's Mill Hospital
Sutton-in-Ashfield, United Kingdom
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Principal Investigator: Mary O'Brien, MD Royal Marsden NHS Foundation Trust
  More Information

Additional Information:
No publications provided

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT01208064     History of Changes
Other Study ID Numbers: EORTC-08092, 2010-018566-23, EU-21072
Study First Received: September 22, 2010
Last Updated: July 3, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Germany: Federal Institute for Drugs and Medical Devices
Slovenia: Ministry of Health
Greece: National Organization of Medicines
Egypt: Ministry of Health and Population
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
adenocarcinoma of the lung
adenosquamous cell lung cancer
bronchoalveolar cell lung cancer
large cell lung cancer
recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 24, 2014