Non Squamous Lung Cancer Clinical Trial
— PROFILE 1014Official title:
Phase 3, Randomized, Open-label Study Of The Efficacy And Safety Of Crizotinib Versus Pemetrexed/Cisplatin Or Pemetrexed/Carboplatin In Previously Untreated Patients With Non-squamous Carcinoma Of The Lung Harboring A Translocation Or Inversion Event Involving The Anaplastic Lymphoma Kinase (Alk) Gene Locus.
| Verified date | September 2017 |
| Source | Pfizer |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This study will evaluate the anti-cancer effects of crizotinib when compared with standard chemotherapy in patients with ALK positive lung cancer.
| Status | Completed |
| Enrollment | 343 |
| Est. completion date | November 30, 2016 |
| Est. primary completion date | November 30, 2013 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Proven diagnosis of locally advanced not suitable for local treatment, recurrent and metastatic non-squamous cell carcinoma of the lung - Positive for translocation or inversion events involving the ALK gene locus - No prior systemic treatment for locally advanced or metastatic disease; Patients with brain metastases only if treated and neurologically stable with no ongoing requirement for corticosteroids - Evidence of a personally signed and dated informed consent document and willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures including completion of patient reported outcome [PRO] measures. - 18 years of age or older with the exception of India which has an upper age limit of 65 years old Exclusion Criteria: - Current treatment on another therapeutic clinical trial. - Prior therapy directly targeting ALK. - Any of the following within the 3 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack. - - Appropriate treatment with anticoagulants is permitted. - Ongoing cardiac dysrhythmias of NCI CTCAE Grade >=2, uncontrolled atrial fibrillation of any grade, or QTc interval >470 msec. - Pregnancy or breastfeeding. - Use of drugs or foods that are known potent CYP3A4 inducers/inhibitors Concurrent use of drugs that are CYP3A4 substrates with narrow therapeutic indices. - Known HIV infection - Known interstitial lung disease or interstitial fibrosis - Other severe acute or chronic medical conditions (including severe gastrointestinal conditions such as diarrhea or ulcer) or psychiatric conditions, or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, and which would, therefore, make the patient inappropriate for entry into this study |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Department of Medical Oncology | Adelaide | South Australia |
| Australia | Macarthur Cancer Therapy Centre | Campbelltown | New South Wales |
| Australia | Chris O'Brien Lifehouse | Camperdown | New South Wales |
| Australia | The Prince Charles Hospital | Chermside | Queensland |
| Australia | The Townsville Hospital | Douglas | Queensland |
| Australia | Peter MacCallum Cancer Centre, Department of Haematology and Medical Oncology | East Melbourne | Victoria |
| Australia | Peninsula & South Eastern Haematology and Oncology Group | Frankston | Victoria |
| Australia | The Royal Brisbane & Womens Hospital | Herston | Queensland |
| Australia | Parkhaven Medical Center | Hyde Park | Queensland |
| Australia | Royal North Shore Hospital | St. Leonards | New South Wales |
| Austria | Klinikum Wels-Grieskirchen | Wels | |
| Belgium | Universitair Ziekenhuis Brussel / Medische Oncologie | Brussel | |
| Belgium | Cliniques Universitaires St Luc | Brussels | |
| Belgium | Institut Jules Bordet, Centre des Tumeurs de l'ULB | Bruxelles | |
| Belgium | Grand Hopital de Charleroi -Site Notre Dame | Charleroi | Hainaut |
| Belgium | UZ Antwerpen-Pneumologie | Edegem | Antwerp |
| Belgium | Universitair Ziekenhuis Gent (U.Z. Gent) | Gent | |
| Belgium | Centre Hospitalier Universitaire de Liege | Liege | |
| Belgium | Department of Pulmonary Diseases AZ Delta | Roeselare | |
| Brazil | Fundacao Pio XII Hospital de Cancer de Barretos | Barretos | São Paulo |
| Brazil | Associacao Hospital de Caridade de Ijui | Ijui | RS |
| Brazil | Hospital Sao Lucas da PUCRS | Porto Alegre | RS |
| Brazil | Instituto Nacional de Cancer - INCA | Rio de Janeiro | RJ |
| Brazil | Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira - ICESP | Sao Paulo | SP |
| Canada | Cross Cancer Institute | Edmonton | Alberta |
| Canada | QEII Health Sciences Centre | Halifax | Nova Scotia |
| Canada | QEII Health Sciences Centre | Halifax | Nova Scotia |
| Canada | Jewish General Hospital | Montreal | Quebec |
| Canada | McGill University Health Centre (MUHC), Glen Site, Cedars Cancer Centre | Montreal | Quebec |
| Canada | R.S. McLaughlin Durham Regional Cancer Centre | Oshawa | Ontario |
| Canada | Institut universitaire de cardiologie et de pneumologie de Quebec (IUCPQ) | Ste-Foy | Quebec |
| Chile | Hospital Clinico Universidad de Chile, Seccion de Oncologia | Independencia | Santiago, Rm |
| Chile | Instituto Nacional del Cancer | Santiago | RM |
| Chile | Instituto Clinico Oncologico del Sur | Temuco | Cautin |
| China | 307 Hospital of PLA | Beijing | Beijing |
| China | Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Beijing | |
| China | Oncology Department, West China Hospital of Sichuan University | Chengdu | Sichuan |
| China | Oncology Center, Guangdong General Hospital | Guangzhou | Guangdong |
| China | No.81 Hospital of the PLA | Nanjing | Jiangsu |
| China | Shanghai Chest Hospital/Department of Pulmonary Medicine | Shanghai | |
| China | Shanghai Pulmonary Hospital/Dept. of Oncology | Shanghai | |
| China | Zhongshan Hospital Fudan University | Shanghai | |
| China | Union Hospital, Tongji Medical College of Huazhong University of Science & Technology/Cancer Center | Wuhan | Hubei |
| Finland | Helsingin yliopistollinen keskussairaala, Meilahden kolmiosairaala,Keuhkosairauksien poliklinikka | Helsinki | |
| Finland | Satakunnan keskussairaala/Keuhkosairauksien osasto A4 | Pori | |
| Finland | Tampereen yliopistollinen sairaala | Tampere | |
| France | Hopital Avicenne | Bobigny Cedex | |
| France | CHU de Caen | Caen Cedex | |
| France | CHU Grenoble | Grenoble Cedex | |
| France | Centre Oscar Lambret | Lille | |
| France | Centre Leon Berard | Lyon Cedex 08 | |
| France | APHM - Hopital Nord / Service d'Oncologie Multidisciplinaire et Innovations Thérapeutiques | Marseille Cedex 20 | |
| France | Hopital Arnaud de Villeneuve / CHU de Montpellier | Montpellier | |
| France | Hopital Tenon, Service de Pneumologie | Paris cedex 20 | |
| France | Nouvel Hopital Civil - HSU - Pôle de Pathologie Thoracique - Service de Pneumologie | Strasbourg | |
| Germany | Zentralklinik Bad Berka GmbH | Bad Berka | |
| Germany | Charite - Universitaetsmedizin Berlin, Campus Mitte | Berlin | |
| Germany | Thoraxklinik am Universitaetsklinikum Heidelberg | Heidelberg | |
| Germany | St.Vincentius-Kliniken Karlsruhe | Karlsruhe | |
| Germany | UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz | Mainz | |
| Germany | Kliniken Maria Hilf GmbH | Moenchengladbach | |
| Germany | Pius-Hospital Oldenburg | Oldenburg | |
| Germany | HSK Dr.- Horst-Schmidt-Kliniken GmbH, | Wiesbaden | |
| Hong Kong | Department of Clinical Oncology, Queen Elizabeth Hospital | Kowloon | |
| Hong Kong | Prince of Wales Hospital | Shatin | New Territories |
| India | The Gujarat Cancer & Research Institute (M.P Shah Cancer Hospital), | Ahmedabad, | Gujarat |
| India | Tata Memorial Centre, Tata Memorial Hospital, | Mumbai | Maharashtra |
| Ireland | Aseptic Compounding Unit | Dublin | |
| Ireland | Department of Medical Oncology | Dublin | |
| Italy | Struttura Operativa Complessa Oncologia Medica A Centro di Riferimento Oncologico | Aviano | Pordenone |
| Italy | Farmacia | Aviano (PN) | |
| Italy | Istituto dei tumori Giovanni Paolo II | Bari | |
| Italy | Unità Operativa di Oncologia Medica Azienda USL Città di Bologna | Bologna | |
| Italy | Azienda Ospedaliero-Universitaria "Mater Domini" | Catanzaro | |
| Italy | Unità Operativa di Farmacia - Campus Salvatore venuta | Catanzaro | |
| Italy | Ospedale Civile Azienda USL Toscana Nord Ovest | Livorno | |
| Italy | Unità Operativa Farmacia Ospedaliera PO di Livorno | Livorno | |
| Italy | Farmacia Istituto Europeo di Oncologia IRCCS, U.O. Farmacia | Milano | |
| Italy | Fondazione IRCCS Istituto Nazionale Tumori, Struttura Complessa di Medicina Oncologica 1 | Milano | |
| Italy | Istituto Europeo di Oncologia | Milano | |
| Italy | Ospedale Niguarda Ca'Granda, Divisione Oncologia Medica Falck | Milano | |
| Italy | A.O.R.N. Ospedale Dei Colli - Monaldi | Napoli | |
| Italy | Farmacia | Napoli | |
| Italy | Azienda Ospedaliera Universitaria San Luigi Gonzaga | Orbassano (TO) | |
| Italy | S.C. Farmacia Ospedaliera , Azienda Ospedaliero Universitaria San Luigi Gonzaga | Orbassano (TO) | |
| Italy | Oncologia Medica, Azienda Ospedaliero- Universitaria di Parma | Parma | |
| Italy | Farmacia Ospedaliera | Perugia | |
| Italy | SC Oncologia Medica, Ospedale Santa Maria della Misericordia | Perugia | |
| Italy | IRCCS -Arcispedale S. Maria Nuova Tecnologie Avanzate e Modelli Assistenziali in Oncologia | Reggio Emilia | |
| Italy | Azienda Ospedaliera San Camillo Forlanini-Padiglione Flaiani | Roma | |
| Italy | Farmacia Interna | Roma | |
| Italy | Istituto Regina Elena, Struttura Complessa Oncologia Medica A | Roma | |
| Italy | Unita Operativa, Oncologia Medica, Istituto di Medicina Interna e Geriatria | Roma | |
| Japan | Hyogo Cancer Center | Akashi | Hyogo |
| Japan | National Cancer Center Hospital | Chuo-Ku | Tokyo |
| Japan | Kyushu University Hospital Respiratory Medicine | Fukuoka | |
| Japan | National Hospital organization Kyushu Cancer Center | Fukuoka | |
| Japan | National Cancer Center Hospital East | Kashiwa | Chiba |
| Japan | The Cancer Institute Hospital of JFCR | Koto-ku | Tokyo |
| Japan | National Hospital Organization Shikoku Cancer Center | Matsuyama | Ehime |
| Japan | Aichi cancer center central hospital | Nagoya | Aichi |
| Japan | Okayama University Hospital | Okayama-city | Okayama |
| Japan | Kinki University Hospital | Osakasayama-shi | Osaka |
| Japan | National Hospital Organization Hokkaido Cancer Center | Sapporo | Hokkaido |
| Japan | Tohoku University Hospital | Sendai | Miyagi |
| Japan | Shizuoka Cancer Center | Sunto-gun | Shizuoka |
| Japan | National Hospital Organization Yamaguchi-Ube Medical Center | Ube-shi | Yamaguchi |
| Japan | Kanagawa Cardiovascular and Respiratory Center | Yokohama | Kanagawa |
| Korea, Republic of | Asan Medical Center | Seoul | |
| Korea, Republic of | Samsung Medical Center, Sungkyunkwan Univ. School of Medicine | Seoul | |
| Korea, Republic of | Seoul National University Hospital | Seoul | |
| Luxembourg | Centre Hospitalier de Luxembourg | Luxembourg | |
| Mexico | Instituto Nacional de Cancerologia | Mexico | D.f. |
| Netherlands | Jeroen Bosch Ziekenhuis | 's Hertogenbosch | NB |
| Netherlands | VUMC | Amsterdam | |
| Netherlands | Academisch Ziekenhuis Maastricht / afdeling longziekten en tuberculose | Maastricht | |
| Norway | Oslo universitetssykehus HF - Radiumhospitalet | Oslo | |
| Peru | Clinica Anglo Americana/Centro de Investigacion Oncologia CAA | San Isidro | Lima |
| Portugal | Centro Hospitalar e Universitario de Coimbra - Hospital Geral | Coimbra | |
| Portugal | Centro Hospitalar de Lisboa Norte - Hospital Pulido Valente | Lisboa | |
| Portugal | Instituto Português de Oncologia de Lisboa, Prof. Francisco Gentil E.P.E. | Lisboa | |
| Portugal | Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E. | Vila Nova de Gaia | |
| Russian Federation | Russian Oncological Research Center N.N. Blokhin | Moscow | |
| Russian Federation | City Clinical Oncology Dispensary | Saint-Petersburg | |
| Russian Federation | City Clinical Oncology Dispensary | Saint-Petersburg | |
| Russian Federation | First Saint-Petersburg State Medical University n.a. I.P. | Saint-Petersburg | |
| Russian Federation | First Saint-Petersburg State Medical University n.a. I.P. Pavlov | Saint-Petersburg | |
| Russian Federation | Russian Scientific Center of Radiology and Surgical Technologies | Saint-Petersburg | |
| Russian Federation | Samara Regional Clinical Oncology Dispensary | Samara | |
| Singapore | National Cancer Centre | Singapore | |
| Singapore | National University Hospital | Singapore | |
| Singapore | OncoCare Cancer Centre | Singapore | |
| Singapore | Parkway Cancer Centre | Singapore | |
| South Africa | Rondebosch Oncology Centre, Rondebosch Medical Centre | Cape Town | |
| South Africa | University of Witwatersrand Oncology | Johannesburg | Gauteng |
| Spain | Hospital Clinic I Provincial de Barcelona | Barcelona | Catalunya |
| Spain | Hospital Universitari Vall D'Hebron | Barcelona | |
| Spain | Hospital General Universitario de Elche | Elche | Alicante |
| Spain | Hospital Universitario Insular de Gran Canaria | Las Palmas de Gran Canaria | |
| Spain | Hospital Doce de Octubre | Madrid | |
| Spain | Hospital Ramon Y Cajal | Madrid | |
| Spain | Hospital Universitario Virgen de La Victoria | Malaga | |
| Spain | Hospital Universitario Virgen Macarena | Sevilla | Andalucia |
| Spain | Hospital Clinico Universitario Lozano Blesa | Zaragoza | Aragon |
| Switzerland | Universitaetsspital Basel | Basel | |
| Switzerland | Luzerner Kantonsspital (LUKS) | Luzern | |
| Switzerland | Kantonsspital Winterthur | Winterthur | |
| Taiwan | Chang Gung Medical Foundation, Kaohsiung Branch | Kaohsiung City | |
| Taiwan | China Medical University Hospital | Taichung | |
| Taiwan | Taichung Veterans General Hospital, Comprehensive Cancer Center | Taichung | |
| Taiwan | Chang Gung Medical Foundation, LinKou Branch | Taoyuan | |
| Ukraine | City Multiple-Discipline Clinical Hospital #4 | Dnipropetrovsk | |
| Ukraine | City Multiple-Discipline Clinical Hospital #4, | Dnipropetrovsk | |
| Ukraine | Department of Oncology and Medical Radiology, SI "DMA of MOH, Ukraine | Dnipropetrovsk | |
| Ukraine | Kyiv City Clinical Oncologic Center/Department of Chemotherapy | Kyiv | |
| Ukraine | Lviv State Oncologic Regional Treatment and Diagnostic Center | Lviv | |
| United Kingdom | Aberdeen Royal Infirmary | Aberdeen | |
| United Kingdom | Addenbrooke's Hospital, Oncology Centre | Cambridge | Cambridgeshire |
| United Kingdom | NHS Greater Glasgow and Clyde Health Board, Beatson West of Scotland Cancer Centre, | Glasgow | Scotland |
| United Kingdom | Ross Hall Hospital | Glasgow | Scotland |
| United Kingdom | Spire Manchester Hospital | Manchester | Lancashire |
| United Kingdom | The Christie Hospital NHS Foundation Trust, Department of Medical Oncology | Manchester | |
| United Kingdom | Mount Vernon Hospital, Mount Vernon Cancer Centre | Northwood | Middlesex |
| United Kingdom | Lister Hospital | Stevenage | Hertfordshire |
| United Kingdom | Queen Elizabeth II Hospital | Welwyn Garden City | Hertfordshire |
| United States | University of New Mexico Cancer Center | Albuquerque | New Mexico |
| United States | UNM Eye Clinic | Albuquerque | New Mexico |
| United States | Georgia Cancer Specialists | Athens | Georgia |
| United States | Georgia Cancer Specialists | Atlanta | Georgia |
| United States | OHSU Knight Cancer Institute | Beaverton | Oregon |
| United States | Tower Cancer Research Foundation | Beverly Hills | California |
| United States | Tower Hematology Oncology Medical Group | Beverly Hills | California |
| United States | Maine Center for Cancer Medicine | Biddeford | Maine |
| United States | Kresge Eye Institute | Bingham Farms | Michigan |
| United States | Lynn Cancer Institute Center for Hematology Oncology | Boca Raton | Florida |
| United States | Maine Center for Cancer Medicine | Brunswick | Maine |
| United States | University of Chicago | Chicago | Illinois |
| United States | Siteman Cancer Center - West County | Creve Coeur | Missouri |
| United States | UT Southwestern Medical Center | Dallas | Texas |
| United States | UT Southwestern Medical Center - Simmons Cancer Center Pharmacy | Dallas | Texas |
| United States | UT Southwestern University Hospital - William P. Clements, Jr. | Dallas | Texas |
| United States | UT Southwestern University Hospital - Zale Lipshy | Dallas | Texas |
| United States | Georgia Cancer Specialists | Decatur | Georgia |
| United States | Karmanos Cancer Institute | Detroit | Michigan |
| United States | Kresge Eye Institute | Detroit | Michigan |
| United States | Tennessee Oncology, PLLC | Dickson | Tennessee |
| United States | Pharma Resource | East Providence | Rhode Island |
| United States | Vincent Armenio | East Providence | Rhode Island |
| United States | Karmanos Cancer Institute at Farmington Hills | Farmington Hills | Michigan |
| United States | CCTAP | Fontana | California |
| United States | Tennessee Oncology, PLLC | Franklin | Tennessee |
| United States | Tennessee Oncology, PLLC | Gallatin | Tennessee |
| United States | OHSU Knight Cancer Institute | Gresham | Oregon |
| United States | Al Fisher, Pharm D. | Harvey | Illinois |
| United States | Ingalls Memorial Hospital | Harvey | Illinois |
| United States | Monroe Medical Associates | Harvey | Illinois |
| United States | Tennessee Oncology, PLLC | Hermitage | Tennessee |
| United States | University of Texas MD Anderson Cancer Center | Houston | Texas |
| United States | Indiana University Hospital | Indianapolis | Indiana |
| United States | Indiana University Melvin and Bren Simon Cancer Center | Indianapolis | Indiana |
| United States | Lois and Eskenazi Hospital | Indianapolis | Indiana |
| United States | NSLIJ Health System/Monter Cancer Center | Lake Success | New York |
| United States | Memorial Medical Center | Las Cruces | New Mexico |
| United States | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire |
| United States | Tennessee Oncology, PLLC | Lebanon | Tennessee |
| United States | Loma Linda University Cancer Center | Loma Linda | California |
| United States | Loma Linda University Cancer Center (LLUCC)-Schuman Pavilion | Loma Linda | California |
| United States | Loma Linda University Medical Center | Loma Linda | California |
| United States | CCTAP | Los Angeles | California |
| United States | Georgia Cancer Specialists | Macon | Georgia |
| United States | University of Wisconsin Hospital and Clinics | Madison | Wisconsin |
| United States | North Shore University Hospital | Manhasset | New York |
| United States | Georgia Cancer Specialists | Marietta | Georgia |
| United States | Hematology-Oncology Associates of Northern New Jersey | Morristown | New Jersey |
| United States | Monroe Medical Association | Munster | Indiana |
| United States | The Community Hospital | Munster | Indiana |
| United States | Tennessee Oncology, PLLC | Murfreesboro | Tennessee |
| United States | Henry-Joyce Cancer Clinic | Nashville | Tennessee |
| United States | Sarah Cannon Research Institute | Nashville | Tennessee |
| United States | Tennessee Oncology, PLLC | Nashville | Tennessee |
| United States | Tennessee Oncology, PLLC | Nashville | Tennessee |
| United States | Tennessee Oncology, PLLC | Nashville | Tennessee |
| United States | Tennessee Oncology, PLLC | Nashville | Tennessee |
| United States | Vanderbilt Oncology Pharmacy | Nashville | Tennessee |
| United States | Long Island Jewish Medical Center | New Hyde Park | New York |
| United States | Ochsner Clinic Foundation | New Orleans | Louisiana |
| United States | Cancer Institute of Florida | Orlando | Florida |
| United States | Florida Hospital | Orlando | Florida |
| United States | Investigational Drug Services | Orlando | Florida |
| United States | Fox Chase Cancer Center | Philadelphia | Pennsylvania |
| United States | OHSU Knight Cancer Institute | Portland | Oregon |
| United States | OHSU Knight Cancer Institute | Portland | Oregon |
| United States | Oregon Health and Science University | Portland | Oregon |
| United States | Barnes-Jewish Hospital | Saint Louis | Missouri |
| United States | Washington University Center for Advanced Medicine Infusion Center Pharmacy | Saint Louis | Missouri |
| United States | Siteman Cancer Center | Saint Peters | Missouri |
| United States | CCTAP | San Diego | California |
| United States | Kaiser Permanente Southern California | San Diego | California |
| United States | Georgia Cancer Specialists | Sandy Springs | Georgia |
| United States | Maine Center for Cancer Medicine | Sanford | Maine |
| United States | Maine Center for Cancer Medicine | Scarborough | Maine |
| United States | Seattle Cancer Care Alliance | Seattle | Washington |
| United States | University of Washington Medical Center | Seattle | Washington |
| United States | Tennessee Oncology, PLLC | Smyrna | Tennessee |
| United States | SUNY Upstate Medical University | Syracuse | New York |
| United States | Monroe Medical Associates | Tinley Park | Illinois |
| United States | OHSU Knight Cancer Institute | Tualatin | Oregon |
| United States | Georgetown University Hospital | Washington, D.C. | District of Columbia |
| United States | Research Pharmacy, Georgetown University Medical Center | Washington, D.C. | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| Pfizer |
United States, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Finland, France, Germany, Hong Kong, India, Ireland, Italy, Japan, Korea, Republic of, Luxembourg, Mexico, Netherlands, Norway, Peru, Portugal, Russian Federation, Singapore, South Africa, Spain, Switzerland, Taiwan, Ukraine, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progression-Free Survival (PFS) Based on IRR | PFS was defined as the time from the date of randomization in study until the date of first documented objective tumor progression (according to RECIST v1.1 as determined by IRR) or death (due to any cause), whichever occurred first. PFS (in months) was calculated as (first event date - randomization date +1)/30.44. Objective progression was defined as a 20 percent (%) increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 millimeter (mm) or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions. | Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months) | |
| Secondary | Overall Survival (OS) | OS (in months) was defined as the duration from start of study treatment to date of death due to any cause. OS = (date of death minus the date of randomization of study medication plus 1) divided by 30.4. For participants who were alive, overall survival was censored on last date the participants were known to be alive. | From randomization to death or last date known alive for those not known to have died (up to 72 months) | |
| Secondary | Overall Survival Probability at Month 12 and 18 | Overall survival probability at Month 12 and 18 was defined as the probability of overall survival at 12 and 18 months respectively, where the OS was defined as the duration from date of randomization to date of death due to any cause. The survival probability was estimated using the Kaplan-Meier method. | Month 12, 18 | |
| Secondary | Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by IRR | ORR was defined as percentage of participants with complete response (CR) or partial response (PR) according to RECIST v1.1 determined by IRR. CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions and disappearance of all non-target lesions. PR was defined as greater than or equal to (>=) 30% decrease taking as reference the baseline sum of lesion dimensions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No clear progression of non-target disease. No new lesions. | Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months) | |
| Secondary | Duration of Response (DR) Based on IRR | DR: time from first documentation of objective tumor response (CR or PR) to first documentation of PD or death due to any cause, whichever occurred first as per RECIST v1.1 determined by IRR. CR: complete disappearance of all target and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions, disappearance of all non-target lesions. PR: >=30% decrease taking as reference the baseline sum of lesion dimensions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all or target lesions. No clear progression of non-target disease. No new lesions. c) PD: 20 % increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions. | From objective response to date of progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months) | |
| Secondary | Time to Tumor Response (TTR) Based on IRR | TTR was defined as the time from randomization to first documentation of objective tumor response (CR or PR) according to RECIST v1.1 determined by IRR. CR: complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions and disappearance of all non-target lesions. PR: >=30% decrease taking as reference the baseline sum of lesion dimensions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all or target lesions. No clear progression of non-target disease. No new lesions. | Randomization to first documentation of objective tumor response (up to 35 months) | |
| Secondary | Percentage of Participants With Disease Control at Week 12 Based on IRR | Disease control rate at week 12 is defined as the percent of participants with CR, PR, or stable disease (SD) at week 12 according to RECIST v1.1 determined by IRR. The best response of SD would be assigned if SD criteria was met at least once after randomization at a minimum interval of 6 weeks. CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions and disappearance of all non-target lesions. PR: >=30% decrease taking as reference the baseline sum of lesion dimensions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. Short axis was used in sum for target nodes, while longest diameter was used in sum for all or target lesions. No clear progression of non-target disease. No new lesions. | Week 12 | |
| Secondary | Time to Progression (TTP) Based on IRR | TTP was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression according to RECIST v1.1 determined by IRR. Objective tumor progression was defined as 20% increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions. If tumor progression data included more than 1 date, the first date was used. TTP (in months) was calculated as (first event date - randomization date +1)/30.44. | Randomization to objective progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months) | |
| Secondary | Time to Intracranial Progression (IC-TTP) Based on IRR | IC-TTP was defined similarly to TTP, but only considering intracranial disease (excluding extracranial disease) and the progression was determined based on either new brain metastases or progression of existing brain metastases. TTP was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression according to RECIST v1.1 determined by IRR. Objective tumor progression was defined as 20% increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions. | Randomization to objective intracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months) | |
| Secondary | Time to Extracranial Progression (EC-TTP) Based on IRR | EC-TTP was defined similarly to TTP, but only considering extracranial disease (excluding intracranial disease) and the progression was determined based on either new extracranial lesions or progression of existing extracranial lesions. TTP was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression according to RECIST v1.1 determined by IRR. Objective tumor progression was defined as 20% increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions. | Randomization to objective extracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months) | |
| Secondary | Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose of study drug that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. | Baseline up to follow up period (up to 72 months) | |
| Secondary | Percentage of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator. | Baseline up to follow up period (up to 72 months) | |
| Secondary | Percentage of Participants With Adverse Events (AEs) According to Maximum Severity | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to maximum severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Grade 1 =mild; Grade 2 =moderate; within normal limits, Grade 3 =severe or medically significant but not immediately life-threatening; Grade 4 =life-threatening or disabling; urgent intervention indicated; Grade 5 =death. | Baseline up to follow up period (up to 72 months) | |
| Secondary | Plasma Predose Concentration (Ctrough) of Crizotinib and Its Metabolite PF-06260182 | Ctrough is the concentration prior to study drug administration on Day 1 of Cycle 2 onwards. PF-06260182 is the metabolite of Crizotinib. | Predose at Day 1 of Cycle 2, 3 and 5 | |
| Secondary | Percentage of Participants For Each Anaplastic Lymphoma Kinase (ALK) Gene Fusion Variants | The Response Genetics, Inc. Echinoderm Microtubule Associated Protein Like 4 (EML4) ALK reverse transcriptase polymerase chain reaction (RT PCR) gene fusion test was used for the analysis of tissue samples for the ALK gene fusion variants (either no rearrangement, or 1 of 9 results reflecting 8 specific rearrangements [V1, V2, V3a, V3b,V3a/b, V4, V5a, V6, V7]). Percentage of participants who tested positive for ALK gene fusion variants were reported in this outcome measure. | 28 days prior to day 1 of study treatment | |
| Secondary | Objective Response Rate (ORR) of Anaplastic Lymphoma Kinase (ALK) Variant Groups Based on IRR | The Response Genetics, Inc. EML4 ALK reverse transcriptase polymerase chain reaction (RT PCR) gene fusion test was used for the analysis of tissue samples for the ALK gene fusion variants (either no rearrangement, or 1 of 9 results reflecting 8 specific rearrangements [V1, V2, V3a, V3b,V3a/b, V4, V5a, V6, V7]). Percentage of participants with confirmed CR or PR according to RECIST v1.1 determined by IRR, by type of ALK gene fusion variant were reported in this outcome measure. CR: complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions and disappearance of all non-target lesions. PR: >=30% decrease decrease taking as reference the baseline sum of lesion dimensions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all or target lesions. No clear progression of non-target disease. No new lesions. | Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months) | |
| Secondary | Time to Deterioration (TTD) in Chest Pain, Dyspnea or Cough | TTD in pain in chest, dyspnea, or cough from the Quality of Life Questionnaire Core 30 (QLQ-LC13) was a composite endpoint defined as the time from randomization to the earliest time the participant's scale scores showed a 10 point or greater increase after baseline in any of the 3 symptoms. For those who had not shown deterioration, the data was censored at the last date when the participants completed an assessment (QLQ-LC13) for pain, dyspnea, or cough or at last visit date prior to crossover for participants randomized to chemotherapy who subsequently crossed over to crizotinib. A 10-point or higher change in the score was perceived by participants as clinically significant. The transformed score of pain, dyspnea, and cough symptom scales of EORTC QLQ-LC13 (European Organization for the Research and Treatment of Cancer) range from 0 to 100, where higher scores indicate greater symptom severity. | From randomization of treatment up to deterioration while on study treatment (up to 35 months) | |
| Secondary | Change From Baseline in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) | EORTC QLQ-C30: included 5 functional scales (physical, role, cognitive, emotional and social), global health status/global quality of life scale, 3 symptom scales (fatigue, pain, nausea and vomiting), 6 single items that assess the additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea) and financial difficulties. All scales and single-item measures range from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning, for the global health status/QoL represents a high QoL (better participant state), and for a symptom scale/item represents a high level of symptoms/problems (worse participant state). | Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months) | |
| Secondary | Change From Baseline Scores in QLQ-C30 Symptoms as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) | EORTC QLQ-C30: included 5 functional scales (physical, role, cognitive, emotional and social), global health status/global quality of life scale, 3 symptom scales (fatigue, pain, nausea and vomiting), 6 single items that assess the additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea) and financial difficulties. All scales and single-item measures range from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning, for the global health status/QoL represents a high QoL (better participant state), and for a symptom scale/item represents a high level of symptoms/problems (worse participant state). | Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months) | |
| Secondary | Change From Baseline in Lung Cancer Symptom Scores as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) | QLQ-LC13 consists of 1 multi-item scale and 9 single items that assess the specific symptoms (dyspnea, cough, hemoptysis, and site-specific pain), side effects (sore mouth, dysphagia, neuropathy, and alopecia), and pain medication use of patients with lung cancer receiving chemotherapy. All multi-item scales and single-item measures range from 0 to 100, where higher score indicates greater degree of symptom severity. | Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months) | |
| Secondary | Change From Baseline in General Health Status as Assessed by EuroQol 5D (EQ-5D)- Visual Analog Scale (VAS) | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. VAS component: participants rated their current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health. | Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months) | |
| Secondary | Percentage of Participants With Hospital Admissions-Healthcare Resource Utilization (HCRU) | Healthcare resource utilization was to be evaluated using the assessment of the following: date and duration of index admission, duration of hospitalization and date of discharge. | Baseline up to follow up period (up to 72 months) | |
| Secondary | Percentage of Participants With Laboratory Test Abnormalities By Maximum Severity: National Cancer Institute Common Terminology Criteria for Adverse Event (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia(grade[g]1:Less than[<] Lower limit of normal[LLN] to 10gram per[/] deciliter[g/dL],g2:<10 to 8g/dL,g3:<8g/dL,g4:lifethreatening);platelet (g1:| Baseline up to follow up period (up to 72 months) |
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| Secondary | Percentage of Participants With Laboratory Test Abnormalities By Maximum Severity: National Cancer Institute Common Terminology Criteria for Adverse Event (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | ALT/AST (Grade[g]1:>ULN-3*ULN,g2:>3-5*ULN,g3:>5-20*ULN,g4:>20*ULN);Alkaline Phosphatase (g1:>ULN-2.5*ULN,g2:>2.5-5*ULN,g3:>5-20*ULN,g4:>20*ULN);Creatinine (g1:>ULN-1.5*ULN,g2:>1.5-3*ULN,g3:>3-6*ULN,g4:>6*ULN);hyperglycemia (g1:>ULN-160,g2:>160-250,g3:>250-500,g4:>500mg/dL);bilirubin(total) (g1:>ULN-1.5*ULN,g2:>1.5-3*ULN,g3:>3-10*ULN,g4:>10*ULN);hypoglycaemia (g1:| Baseline up to follow up period (up to 72 months) |
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