NCT01639001

Brief Summary

This is a Phase III, Randomized, Open-label, Efficacy and Safety Study of Crizotinib single agent versus Chemotherapy Regimens (Pemetrexed/Cisplatin or Pemetrexed/Carboplatin) in First-Line ALK (Anaplastic Lymphoma Kinase) Positive East Asian Non-Small Cell Lung Cancer Patients. The objective of the study is to demonstrate that Crizotinib is superior to first-line chemotherapy pemetrexed/cisplatin or pemetrexed/carboplatin in prolonging Progression Free Survival (PFS) in East Asian patients with advanced Non-Squamous NSCLC whose tumors harbor a translocation or inversion event involving the ALK (Anaplastic Lymphoma Kinase) gene locus.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
207

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Sep 2012

Longer than P75 for phase_3

Geographic Reach
5 countries

47 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 10, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 12, 2012

Completed
3 months until next milestone

Study Start

First participant enrolled

September 29, 2012

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2015

Completed
1.7 years until next milestone

Results Posted

Study results publicly available

March 13, 2017

Completed
2.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 8, 2020

Completed
Last Updated

December 8, 2020

Status Verified

November 1, 2020

Enrollment Period

2.8 years

First QC Date

July 10, 2012

Results QC Date

June 8, 2016

Last Update Submit

November 16, 2020

Conditions

Keywords

CrizotinibALK positiveALKAnaplastic Lymphoma KinaseNSCLCNon-Small Cell Lung CancerFrontline1LPreviously UntreatedEast AsianNon-Squamous

Outcome Measures

Primary Outcomes (1)

  • Progression-Free Survival (PFS) Based on IRR by Treatment Arm

    PFS was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression (by IRR) or death on study due to any cause, whichever occured first. If tumor progression data included more than 1 date, the first date was used. PFS (in months) was calculated as (first event date - randomization date +1)/30.44. Progression is defined using RECIST v1.1, as at least a 20% increase (including an absolute increase of at least 5 millimeters) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.

    Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (whichever occurred first, assessed up to 33 months)

Secondary Outcomes (19)

  • Objective Response Rate (ORR) - Percentage of Participants With Objective Response Based on IRR

    Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (assessed up to 33 months)

  • Overall Survival (OS)

    From randomization to death or last date known as alive for those who were lost to follow-up or withdrew consent (assessed up to 64 months).

  • Percentage of Participants With Disease Control at 12 Weeks Based on IRR

    From randomization to Week 12

  • Estimate of the Percentage of Participants Surviving at 1 Year and at 18 Months

    From randomization to 1 year and from randomization to 18 months

  • Duration of Response (DR) Based on IRR

    From objective response to date of progression, death or last tumor assessment without progression before any additional anti-cancer therapy (whichever occurred first, up to 33 months)

  • +14 more secondary outcomes

Study Arms (2)

Crizotinib

EXPERIMENTAL

Crizotinib

Drug: Crizotinib

Chemotherapy

ACTIVE COMPARATOR

Chemotherapy \[Option at Investigator's Choice\]

Drug: Pemetrexed/CisplatinDrug: Pemetrexed/Carboplatin

Interventions

250 mg two times daily \[BID\], oral, on a continuous daily dosing schedule. Cycles are defined in 21 day periods.

Crizotinib

Option 1: Pemetrexed/Cisplatin; Pemetrexed, 500 mg/m\^2, will be administered by intravenous infusion over 10 minutes or according to institutional administration timing on Day 1 of a 21-day cycle. Cisplatin, 75 mg/m\^2 will be administered by infusion after adequate hydration according to institutional practices beginning approximately 30 minutes after the end of the pemetrexed infusion. Pemetrexed and cisplatin will be repeated every 3 weeks for a maximum of 6 cycles.

Chemotherapy

Option 2: Pemetrexed/Carboplatin. Pemetrexed, 500 mg/m\^2, will be administered by intravenous infusion over 10 minutes or according to institutional administration timing on Day 1 of a 21-day cycle. Carboplatin, at a dose calculated to produce an AUC of 5 or 6 mg.min/mL will be administered by infusion according to institutional practices beginning approximately 30 minutes after the end of the pemetrexed infusion. Pemetrexed and carboplatin will be repeated every 3 weeks for a maximum of 6 cycles.

Chemotherapy

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically or cytologically 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.

You may not qualify if:

  • 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.
  • 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 CYP3A inducers/inhibitors Concurrent use of drugs that are CYP3A substrates with narrow therapeutic indices.
  • Known HIV infection
  • History of extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis, but not history of prior radiation pneumonitis.
  • Other severe acute or chronic medical conditions (including severe gastrointestinal conditions such as diarrhea or ulcer) or psychiatric conditions, or end-stage renal disease on hemodialysis, 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (47)

The First Affiliated Hospital of Anhui Medical University, Department of Medical Oncology

Hefei, Anhui, 230002, China

Location

Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

Location

Dept. of Respiration. Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100032, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100032, China

Location

Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

Location

Beijing Chest Hospital, Capital Medical University

Beijing, Beijing Municipality, 101149, China

Location

Oncology Department, the Second Affiliated Hospital of Third Military Medical University,PLA

Chongqing, Chongqing Municipality, 400037, China

Location

Oncology Department, XinQiao Hospital of Third Military Medical University,

Chongqing, Chongqing Municipality, 400037, China

Location

Fujian Province Oncology Hospital

Fuzhou, Fujian, 350014, China

Location

SUN Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Guangdong General Hospital, Oncology Center

Guangzhou, Guangdong, 510080, China

Location

The First Affiliated Hospital of Guangzhou Medical College/Thoracic Surgery

Guangzhou, Guangdong, 510120, China

Location

Department 2 of Chemotherapy, Tumour Hospital of Guangxi Zhuang Autonomous Region

Nanning, Guangxi, 530021, China

Location

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology/Cancer Center

Wuhan, Hubei, 430030, China

Location

Hunan Provincial Tumor Hospital/Division of Oncology

Changsha, Hunan, 410013, China

Location

Nanjing General Hospital of Nanjing Military Command, Department of Respiratory medicine

Nanjing, Jiangsu, 210002, China

Location

Department of Oncology, Jilin Provincial Cancer Hospital

Changchun, Jilin, 130012, China

Location

The first hospital of China Medical University/Oncology Department

Shenyang, Liaoning, 110001, China

Location

Oncology Department, West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

Location

Sichuan Province Cancer Hospital/Department of Pulmonary Tumor

Chengdu, Sichuan, 610041, China

Location

Department of Respiratory, The First Affiliated Hospital of College of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

Sir Run Run Shaw Hospital of College of Medicine of Zhejiang University, Center for Oncology

Hangzhou, Zhejiang, 310016, China

Location

307 Hospital of PLA/Department of Lung Cancer

Beijing, 100071, China

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

The Military General Hospital of Beijing PLA

Beijing, 100700, China

Location

Peking Union Medical College Hospital

Beijing, 100730, China

Location

Chinese PLA General Hospital

Beijing, 100853, China

Location

Beijing Chest Hospital, Capital Medical University

Beijing, 101149, China

Location

Respiration department,the First Affiliated Hospital of Third Military Medical University, PLA

Chongqing, 400038, China

Location

Shanghai Chest Hospital/Lung cancer clinical center

Shanghai, 200030, China

Location

Shanghai Chest Hospital

Shanghai, 200030, China

Location

Zhongshan Hospital Fudan University / Respiratory Department

Shanghai, 200032, China

Location

Shanghai First People's Hospital

Shanghai, 200080, China

Location

Tianjin Medical University Cancer Institute and Hospital

Tianjin, 300060, China

Location

Pamela Youde Nethersole Eastern Hospital

Chai Wan, 0, Hong Kong

Location

Queen Mary Hospital

Hong Kong, 0, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

Department of Nuclear Medicine, Radiotherapy and Oncology, Hospital Universiti Sains Malaysia

Kubang Kerian, Kota Bahru, Kelantan, 16150, Malaysia

Location

Hospital Pulau Pinang

George Town, Pulau Pinang, 10990, Malaysia

Location

Chi Mei Medical Center Liouying

Liou Ying Township, Tainan, 736, Taiwan

Location

Chung Shan Medical University Hospital

Taichung, 402, Taiwan

Location

Chi Mei Medical Center Liuying

Tainan, 736, Taiwan

Location

Taipei Veterans General Hospital, Chest Department

Taipei, 11217, Taiwan

Location

Chang Gung Medical Foundation, LinKou Branch

Taoyuan District, 333, Taiwan

Location

Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University

Pathumwan, Bangkok, 10330, Thailand

Location

Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Siriraj Hospital,

Bangkok, 10700, Thailand

Location

Related Publications (1)

  • Wu YL, Lu S, Lu Y, Zhou J, Shi YK, Sriuranpong V, Ho JCM, Ong CK, Tsai CM, Chung CH, Wilner KD, Tang Y, Masters ET, Selaru P, Mok TS. Results of PROFILE 1029, a Phase III Comparison of First-Line Crizotinib versus Chemotherapy in East Asian Patients with ALK-Positive Advanced Non-Small Cell Lung Cancer. J Thorac Oncol. 2018 Oct;13(10):1539-1548. doi: 10.1016/j.jtho.2018.06.012. Epub 2018 Aug 14.

Related Links

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

CrizotinibPemetrexedCisplatinCarboplatin

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

PiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsAminopyridinesPyridinesGuanineHypoxanthinesPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingGlutamatesAmino Acids, AcidicAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, DicarboxylicChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsCoordination ComplexesOrganic Chemicals

Results Point of Contact

Title
Pfizer ClinicalTrials.gov Call Center
Organization
Pfizer, Inc.

Study Officials

  • Pfizer CT.gov Call Center

    Pfizer

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 10, 2012

First Posted

July 12, 2012

Study Start

September 29, 2012

Primary Completion

June 30, 2015

Study Completion

January 8, 2020

Last Updated

December 8, 2020

Results First Posted

March 13, 2017

Record last verified: 2020-11

Data Sharing

IPD Sharing
Will share

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

More information

Locations