A Phase 2, Multicenter, Randomized Study of AP26113
This trial is active, not recruiting.
|Conditions||non-small cell lung cancer, lung cancer, advanced malignancies, carcinoma|
|Targets||ALK, EGFR, ROS1|
|Start date||March 2014|
|End date||November 2016|
|Trial size||218 participants|
|Trial identifier||NCT02094573, AP26113-13-201|
The purpose of this study is to evaluate the efficacy and safety of two different dosing regimens of AP26113 in patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on therapy with crizotinib.
|United States||No locations recruiting|
|Other countries||No locations recruiting|
|Scottsdale, AZ||Mayo Clinic Arizona (Site 229)||no longer recruiting|
|Duarte, CA||City of Hope Comprehensive Cancer Center||no longer recruiting|
|La Jolla, CA||Moores Cancer Center University of California, San Diego (Site 099)||no longer recruiting|
|Orange, CA||UC Irvine Health / Chao Family Comprehensive Cancer Center||no longer recruiting|
|San Diego, CA||University of California San Diego||no longer recruiting|
|San Diego, CA||Kaiser Permanente (Site 208)||no longer recruiting|
|Aurora, CO||University of Colorado Cancer Center - Anschutz Cancer Pavilion||no longer recruiting|
|New Haven, CT||Yale Cancer Center (Site 033)||no longer recruiting|
|New Haven, CT||Yale University||no longer recruiting|
|Lake Worth, FL||Cancer Center of South Florida (Site 204)||no longer recruiting|
|Tampa, FL||Moffitt Cancer Center||no longer recruiting|
|Atlanta, GA||Emory University / Winship Cancer Institute||no longer recruiting|
|Chicago, IL||University of Chicago Comprehensive Cancer Center||no longer recruiting|
|Rochester, MN||Mayo Clinic||no longer recruiting|
|Chapel Hill, NC||UNC Health Care; N.C. Cancer Hospital Infusion/Inpatient Pharmacy (CHIP) (Site 032)||no longer recruiting|
|Charlotte, NC||Novant Health Presbyterian Medical Center||no longer recruiting|
|Chapel Hill, NC||UNC Lineberger Comprehensive Cancer Center||completed|
|Philadelphia, PA||Hospital of the University of Pennsylvania, Perelman Center for Advanced Medicine (Site 013)||no longer recruiting|
|Houston, TX||M D Anderson Cancer Center||no longer recruiting|
|Seattle, WA||Swedish Cancer Institute (Site 211)||no longer recruiting|
|Camperdown, Australia||Chris O'Brien Lifehouse||no longer recruiting|
|Gosford, Australia||Central Coast Cancer Centre, Gosford Hospital (Site 402)||no longer recruiting|
|Kogarah, Australia||The St George Hospital, Cancer Care Center (Site 403)||no longer recruiting|
|St. Leonards, Australia||Royal North Shore Hospital||no longer recruiting|
|Woolloongabba, Australia||Priness Alexandra Hospital, Cancer Services (Site 942)||no longer recruiting|
|Fitzroy, Australia||St Vincent's Hospital Melbourne (Site997)||no longer recruiting|
|Frankston, Australia||Peninsula & South Eastern Haematology Group (Site 994)||no longer recruiting|
|Heidelberg, Australia||Austin Health, Austin Hospital ((Site 999)||no longer recruiting|
|Salzburg, Austria||St.-Johanns-Spital, Universitatsklinik fur Pneumologie/Lungenheilkunde (Site 627)||no longer recruiting|
|Wien, Austria||SMZ Baumgartner Hohe Otto Wagner Spital, Onkologische Ambulanz+Tagesklinik (Site 612)||no longer recruiting|
|Gent, Belgium||University Hospital Gent||no longer recruiting|
|Roeselare, Belgium||H.-Hartziekenhuis Roeselare-Menen vzw (Site 617)||no longer recruiting|
|Ottawa, Canada||The Ottawa Hospital Cancer Centre (Site 131)||no longer recruiting|
|Toronto, Canada||Princess Margaret Cancer Center||no longer recruiting|
|DK 2730 Herlev, Denmark||Herlev Hospital (Site 614)||no longer recruiting|
|Odense C, Denmark||Odense University Hospital (Site 615)||no longer recruiting|
|Caen Cedex, France||Chu de Caen, Service de pneumologie (Site 611)||no longer recruiting|
|Caen Cedex 05, France||Centre Francois Baclesse, Service de Pneumologie (Site 568)||no longer recruiting|
|Grenoble cedex 9, France||CHU de Grenoble - hospital Michallon (Site 569)||no longer recruiting|
|Lyon cedex 08, France||Centre Leon Berard, Departement d'oncologie Medicale (Site 746)||no longer recruiting|
|Nice Cedex 2, France||Centre Antoine Lacassagne (Site 570)||no longer recruiting|
|Paris Cedex 14, France||Hopital Cochin, Service d'oncolgie Medicale du Pr Goldwasser (Site 616)||no longer recruiting|
|Poitiers Cedex, France||CHU de Poitiers (Site 605)||no longer recruiting|
|Rouen, France||CHU de Rouen, Hospital Charles Nicolle, Service de Pneumologie (Site 585)||no longer recruiting|
|Strasbourg Cedex, France||Nouvel Hopital Civil (Site 610)||no longer recruiting|
|Berlin, Germany||Evangelische Lungenklinik Berlin (Site 588)||no longer recruiting|
|Halle, Germany||Krankenhaus Martha Marie Halle (Site 572)||no longer recruiting|
|Heidelberg, Germany||Thoraxklinik-Heidelberg gGmbH, Innere Medizin - Onkologie (Site 586)||no longer recruiting|
|Hemer, Germany||Lungenklinik Hemer, Zentrum fur Pneumologie und Thoraxchirurgie (Site 620)||no longer recruiting|
|Kassel, Germany||Klinikum Kassel GmbH, Klinik fur Onkologie und Hamatologie (Site 573)||no longer recruiting|
|Koln, Germany||Kliniken der Stadt Koln gGmbH, Lungenkrebszentrum Koln-Merheim (Site 626)||no longer recruiting|
|Munchen, Germany||LMU - Klinikum der Universitat Munchen, Campus Innenstadt, Medizinische Klinik V, Pneumologie (Site 609)||no longer recruiting|
|Hong Kong, Hong Kong||Queen Mary Hospital, Division of Respiratory and Critical Care Medicine (Site 973)||no longer recruiting|
|Kowloon, Hong Kong||Queen Elizabeth Hospital, Department of Clinical Oncology (Site 987)||no longer recruiting|
|Kowloon, Hong Kong||Queen Elizabeth Hospital (Site 987)||no longer recruiting|
|Brindisi, Italy||U.O.C. Oncologia Medica, Ospedale A. Perrino, Presidio Ospedaliero Di Summa - Perrino, Azienda Sanitaria Locale di Brindisi (Site 629)||no longer recruiting|
|Livorno, Italy||U.O. Oncologia Medica Azienda USL 6 Livorno, Presidio Ospedaliero di Livorno (Site 576)||no longer recruiting|
|Meldola (FC), Italy||U.O. Oncologia Medica, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)_IRCCS (Site 575)||no longer recruiting|
|Milano, Italy||Dipartimento di Oncologia Medica Ospedale San Raffaele, Istituto di Ricovero e Cura a Carattere Scientifico (Site 578)||no longer recruiting|
|Milano, Italy||Divisione Oncologia Toracica, Istituto Europeo di Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico (Site608)||no longer recruiting|
|Novara, Italy||SC Oncologia Medica, Azienda Ospedaliero-Universitaria Maggiore della Carita di Novara (Site 574)||no longer recruiting|
|Parma, Italy||Struttura Complessa Oncologia Medica Azienda Ospedaliero-Universitaria di Parma (Site 607)||no longer recruiting|
|Rome, Italy||Oncologia Medica A, IRCCS, Istituti Fisioterapici Ospitalieri (Site 632)||no longer recruiting|
|Rome, Italy||U.O.C. di Oncologia, Azienda Ospedaliera Sant'Andrea (Site 631)||no longer recruiting|
|Aviano, Italy||S.O.C. Oncologia Medica A, Centro di Riferimento Oncologico, I.R.C.C.S., Istituto Nazionale Tumori (Site 624)||no longer recruiting|
|Goyang-si, Korea, Republic of||National Cancer Center (Site 916)||no longer recruiting|
|Seoul, Korea, Republic of||Seoul National University Hospital (Site 915)||no longer recruiting|
|Seoul, Korea, Republic of||Severance Hospital, Yonsei University Health System (Site 913)||no longer recruiting|
|Seoul, Korea, Republic of||The Catholic University of Korea Seoul St. Mary's Hospital (Site 938)||no longer recruiting|
|Seoul, Korea, Republic of||Asan Medical Center (Site 917)||no longer recruiting|
|Amsterdam, Netherlands||The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (Site 579)||no longer recruiting|
|Groningen, Netherlands||University Medical Center Groningen (Site 581)||no longer recruiting|
|Masstricht, Netherlands||Maastricht UMC+ (Site 580)||no longer recruiting|
|Amsterdam, Netherlands||VU Medical Center (Site 948)||no longer recruiting|
|Oslo, Norway||Oslo Universitetssykehus HF, Radiumhospitalet (Site 630)||no longer recruiting|
|Singapore, Singapore||National Cancer Centre Singapore, Depart of Medical Oncology (Site 989)||no longer recruiting|
|Singapore, Singapore||OncoCare Cancer Centre (Site 988)||no longer recruiting|
|Alicante, Spain||Hospital General Universitario de Alicante (Site 591)||no longer recruiting|
|Barcelona, Spain||Hospital Universitario Quiron Dexeus, Servicio de Oncologia Medica (Site 590)||no longer recruiting|
|Barcelona, Spain||Hospital Universitari de la Vall d'Hebron Servicio de Oncologia Medica (Site 503)||no longer recruiting|
|Madrid, Spain||Hospital Universitario 12 de Octubre Oncologia Medica (Site 537)||no longer recruiting|
|Madrid, Spain||Hospital Universitario La Paz (Site 582)||no longer recruiting|
|Palma de Mallorca, Spain||Hospital Son Llatzer (Site 625)||no longer recruiting|
|Sevilla, Spain||Hospital Universitario Virgen del Rocio (Site 592)||no longer recruiting|
|Valencia, Spain||Hospital Clinico Universitario de Valencia (Site 589)||no longer recruiting|
|A Coruna, Spain||Hospital Teresa Herrera (Site 554)||no longer recruiting|
|Majadahonda, Spain||Hospital Universitario Puerta de Hierro-Majahahonda (Site 634)||no longer recruiting|
|Goteborg, Sweden||Sahlgrenska Universitetssjukhuset (Site 758)||no longer recruiting|
|Stockholm, Sweden||Karolinska Universitetssjukhuset||no longer recruiting|
|Bern, Switzerland||Inselspital - Universitatsspital Bern||no longer recruiting|
|Winterthur, Switzerland||Kantonsspital Winterthur||no longer recruiting|
|Birmingham, United Kingdom||Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust (Site 721)||no longer recruiting|
|London, United Kingdom||University College London Hospital (Site 628)||no longer recruiting|
|Manchester, United Kingdom||The Christie NHS Foundation Trust (Site 725)||no longer recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||parallel assignment|
Objective response rate (ORR)
time frame: Confirmed ≥4 weeks after initial response. Until discontinuation or the end of the study.
Overall survival (OS)
time frame: Until the end of the study or death.
Progression-free survival (PFS)
time frame: Until the end of the study or disease progression or death due to any cause.
Health-related quality of life (HRQoL)
time frame: Until 30 days after the last dose of study treatment.
time frame: Until the end of the treatment.
PK parameters of steady-state plasma concentration.
time frame: At designated time points in dosing Cycles 2, 3, 4 and 5.
Male or female participants at least 18 years old.
- Have histologically or cytologically confirmed locally advanced or metastatic NSCLC that is ALK+.
- Must meet one of the following two criteria:
- Have documented ALK rearrangement by a positive result from the Vysis® ALK Break-Apart fluorescence in situ hybridization (FISH) Probe Kit; or
- Have documented ALK positivity by a different test and tissue available for the Vysis® FISH test. Tissue should be derived preferably from a biopsy taken after progression with crizotinib. If such a sample is not available, testing may be performed with archived tumor tissue.
- Had progressive disease while on crizotinib, as assessed by the investigator or treating physician.
- Have at least 1 measurable lesion per RECIST v1.1. Note: Previously irradiated lesions may not be used for target lesions, unless there is unambiguous radiological progression after radiotherapy. Brain lesions may not be used as target lesions if they were: 1) previously treated with whole brain radiation therapy (WBRT) within 3 months, or 2) previously treated by stereotactic radiosurgery (SRS) or surgical resection.
- Recovered from toxicities related to prior anticancer therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v4.0) grade ≤2.
- Are a male or female patient ≥18 years old.
- Have a life expectancy ≥3 months.
- Have adequate organ and hematologic function, as determined by:
- Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN; ≤5 x ULN is acceptable if liver metastases are present)
- Total serum bilirubin ≤1.5 x ULN (<3.0 x ULN for patients with Gilbert syndrome)
- Serum creatinine ≤1.5 x ULN
- Serum lipase/amylase ≤1.5 x ULN
- Absolute neutrophil count (ANC) ≥1500/µL
- Platelets ≥75000/µL
- Hemoglobin ≥10 g/dL
- Have Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
- Have normal QT interval on screening electrocardiogram (ECG) evaluation, defined as QT interval corrected (Fridericia) (QTcF) of ≤450 ms in males or ≤470 ms in females.
- For female patients of childbearing potential, a negative pregnancy test must be documented prior to enrollment.
- Female and male patients who are fertile must agree to use a highly effective form of contraception with their sexual partners throughout study participation.
- Must provide a signed and dated informed consent indicating that the patient has been informed of all pertinent aspects of the study, including the potential risks, and is willingly participating.
- Have the willingness and ability to comply with scheduled visits and study procedures.
- Received any prior ALK-targeted TKI other than crizotinib.
- Received crizotinib within 3 days of the first dose of AP26113 (Day 1, Cycle 1).
- Received cytotoxic chemotherapy, investigational agents, or radiation within 14 days, except SRS or stereotactic body radiosurgery.
- Received monoclonal antibodies or had major surgery within 30 days of the first dose of AP26113 (Day 1, Cycle 1).
- Have been diagnosed with another primary malignancy within the past 3 years (except for adequately treated non-melanoma skin cancer, cervical cancer in situ, or prostate cancer, which are allowed within 3 years).
- Have symptomatic CNS metastases that are neurologically unstable or require an increasing dose of corticosteroids.
- Have current spinal cord compression.
- Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
- Myocardial infarction (MI) within 6 months prior to the first dose of AP26113
- Unstable angina within 6 months prior to first dose
- Congestive heart failure (CHF) within 6 months prior to first dose
- History of clinically significant (as determined by the treating physician) atrial arrhythmia
- Any history of ventricular arrhythmia
- Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose
- Have a history or the presence of pulmonary interstitial disease or drug-related pneumonitis.
- Have an ongoing or active infection. The requirement for intravenous (IV) antibiotics is considered active infection.
- Have a known history of human immunodeficiency virus (HIV). Testing is not required in the absence of history.
- Have a history of or active significant gastrointestinal (GI) bleeding within 3 months of the first dose of AP26113.
- Have a known or suspected hypersensitivity to AP26113 or its excipients.
- Have malabsorption syndrome or other GI illness that could affect oral absorption of the study drug.
- Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with evaluation of the drug study.
- Be pregnant or breastfeeding.
|Official title||A Randomized Phase 2 Study of AP26113 in Patients With ALK-positive, Non-small Cell Lung Cancer (NSCLC) Previously Treated With Crizotinib|
|Description||This is a randomized, phase 2, open-label, multicenter, international study to evaluate the efficacy and safety of two different dosing regimens of AP26113 in patients with ALK-positive, locally advanced or metastatic NSCLC who have previously been treated with crizotinib. The primary objective of the study is to determine the efficacy of AP26113, as evidenced by confirmed objective response rate (ORR), as assessed by the investigator, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Two dosing regimens will be tested. The secondary objectives of the study (for each dosing regimen) include confirmed ORR, as assessed by a central independent review committee (IRC), per RECIST v1.1; CNS response (ORR and progression free survival [PFS]), per RECIST v1.1, in patients with active brain metastases); time to/duration of response; time on treatment; disease control rate, per RECIST v.1.1; PFS; overall survival (OS); safety and tolerability; population pharmacokinetics (PK); and patient-reported symptoms of lung cancer and health-related quality of life (HRQoL). Exploratory objectives (for each dosing regimen) include correlation of AP26113 exposure with both efficacy and safety and correlation of tumor and plasma biomarkers with AP26113 efficacy and safety. It is estimated that accrual will be completed within 18 months; the total estimated duration of the study is 3 years.|
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