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

NCT01208064 | Terminated Phase 2

• 3 other identifiers: EORTC-080922010-018566-23EU-21072
• Study Type: interventional
• Target: 102
• Locations: 8 countries
• Sites: 22

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.

Conditions

Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall survival

Secondary Outcomes (6)

• 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

Study Arms (2)

Pazopanib

EXPERIMENTAL

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

PLACEBO COMPARATOR

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

Interventions

pazopanib hydrochloride DRUG

Pazopanib

laboratory biomarker analysis OTHER

Pazopanib; Placebo

pharmacogenomic studies OTHER

Pazopanib; Placebo

pharmacological study OTHER

Pazopanib; Placebo

quality-of-life assessment PROCEDURE

Pazopanib; Placebo

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (22)

Universitair Ziekenhuis Gent

Ghent, Belgium

Location

Centre Hospitalier Regional De La Citadelle

Liège, Belgium

Location

Clinique et Maternité Sainte Elisabeth

Namur, Belgium

Location

National Cancer Institute

Cairo, Egypt

Location

Centre Georges-Francois-Leclerc

Dijon, France

Location

Assistance Publique - Hôpitaux de Marseille - Assistance Publique - Hôpitaux de Marseille - Hopital Nord

Marseille, France

Location

Klinik Loewenstein

Löwenstein, Germany

Location

UniversitaetsMedizin Mannheim

Mannheim, Germany

Location

University General Hospital Heraklion

Heraklion, Greece

Location

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis

Amsterdam, Netherlands

Location

Amphia Ziekenhuis

Breda, Netherlands

Location

Isala Klinieken

Zwolle, Netherlands

Location

University Clinic Golnik

Golnik, Slovenia

Location

Royal Marsden - Surrey

Sutton, England, SM2 5PT, United Kingdom

Location

Western General Hospital

Edinburgh, United Kingdom

Location

Guy's and St Thomas' NHS

London, United Kingdom

Location

Royal Marsden Hospital

London, United Kingdom

Location

Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

Location

Weston Park Hospital

Sheffield, United Kingdom

Location

Royal Marsden Hospital

Sutton, United Kingdom

Location

King's Mill Hospital

Sutton in Ashfield, United Kingdom

Location

MeSH Terms

Conditions

Lung Neoplasms; Adenocarcinoma of Lung; Adenocarcinoma, Bronchiolo-Alveolar; Carcinoma, Non-Small-Cell Lung

Interventions

Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Mary O'Brien, MD

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2010
• First Posted: September 23, 2010
• Study Start: July 1, 2011
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: July 12, 2018

Record last verified: 2018-07

Locations

BE (3); EG (1); SL (1); NL (3); GR (1); FR (2); GB (9); DE (2)