A Clinical Trial Testing The Efficacy Of Crizotinib Versus Standard Chemotherapy Pemetrexed Plus Cisplatin Or Carboplatin In Patients With ALK Positive Non Squamous Cancer Of The Lung (PROFILE 1014)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01154140
First received: June 29, 2010
Last updated: March 20, 2015
Last verified: March 2015
Results First Received: November 26, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Non Squamous Lung Cancer
Intervention: Drug: treatment

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This phase 3, randomized, open label, multicenter study conducted at 169 centers in 31 countries. A total of 343 participants were randomized, 172 in crizotinib arm and 171 in chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) arm. Date of first randomization was 13 January 2011. This study is ongoing at data cut off 30 November 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with histologically or cytologically proven diagnosis of locally advanced, recurrent, or metastatic non squamous non small cell lung cancer and tumors with measurable disease were enrolled. Participants were to be positive for translocation or inversion events involving the ALK gene locus as determined by an ALK break‑apart FISH test.

Reporting Groups
  Description
Crizotinib Crizotinib capsules, 250 mg twice daily (BID), were administered orally at approximately the same time each day on a continuous daily dosing schedule. Each treatment cycle was defined as 3 weeks. Participants could continue crizotinib treatment beyond the time of RECIST defined Progressive Disease (PD), as determined by independent radiology review (IRR), at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Chemotherapy Standard doses of chemotherapy were administered by intravenous (IV) infusion. Pemetrexed (500 mg/m2) was administered over 10 minutes or according to institutional administration timing; cisplatin (75 mg/m2) was administered after adequate hydration beginning approximately 30 minutes after the end of the pemetrexed infusion and carboplatin was administered at a dose calculated to produce an area under the concentration time curve [AUC] of 5 or 6 mg*min/mL, beginning approximately 30 minutes after end of pemetrexed infusion.

Participant Flow:   Overall Study
    Crizotinib     Chemotherapy  
STARTED     172     171  
Treated     171     169  
COMPLETED     0     0  
NOT COMPLETED     172     171  
Death                 44                 46  
Lost to Follow-up                 0                 2  
Withdrawal by Subject                 7                 5  
Not specified                 1                 1  
Ongoing at date of cut-off                 119                 115  
Randomized but not treated                 1                 2  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Crizotinib Crizotinib capsules, 250 mg twice daily (BID), were administered orally at approximately the same time each day on a continuous daily dosing schedule. Each treatment cycle was defined as 3 weeks. Participants could continue crizotinib treatment beyond the time of RECIST defined Progressive Disease (PD), as determined by independent radiology review (IRR), at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Chemotherapy Standard doses of chemotherapy were administered by intravenous (IV) infusion. Pemetrexed (500 mg/m2) was administered over 10 minutes or according to institutional administration timing; cisplatin (75 mg/m2) was administered after adequate hydration beginning approximately 30 minutes after the end of the pemetrexed infusion and carboplatin was administered at a dose calculated to produce an area under the concentration time curve [AUC] of 5 or 6 mg*min/mL, beginning approximately 30 minutes after end of pemetrexed infusion.
Total Total of all reporting groups

Baseline Measures
    Crizotinib     Chemotherapy     Total  
Number of Participants  
[units: participants]
  172     171     343  
Age  
[units: Years]
Mean (Standard Deviation)
  50.94  (11.9)     52.89  (13.1)     51.92  (12.6)  
Gender  
[units: Participants]
     
Female     104     108     212  
Male     68     63     131  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Progression-Free Survival (PFS) Based on Independent Radiology Review (IRR) by Treatment Arm   [ Time Frame: Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months) ]

2.  Secondary:   Overall Survival (OS)   [ Time Frame: From randomization to death or last date known alive for those not known to have died (up to 35 months) ]

3.  Secondary:   OS Probability at Months 12 and 18   [ Time Frame: Months 12 and 18 ]

4.  Secondary:   Objective Response Rate - Percentage of Participants With Objective Response as Assessed by IRR   [ Time Frame: Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months) ]

5.  Secondary:   Duration of Response (DR) Based on IRR   [ Time Frame: From objective response to date of progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months). ]

6.  Secondary:   Time to Tumor Response (TTR) Based on IRR   [ Time Frame: Randomization to first documentation of objective tumor response (up to 35 months) ]

7.  Secondary:   Percentage of Participants With Disease Control at Week 12 Based on IRR   [ Time Frame: From randomization to Week 12 ]

8.  Secondary:   Time to Progression (TTP) Based on IRR   [ Time Frame: Randomization to objective progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months) ]

9.  Secondary:   Time to Intracranial Progression (IC-TTP) Based on IRR   [ Time Frame: Randomization to objective intracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months) ]

10.  Secondary:   Time to Extracranial Progression (EC-TTP) Based on IRR   [ Time Frame: Randomization to objective extracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months) ]

11.  Secondary:   Percentage of Participants With Treatment-emergent Adverse Events (AEs; All Causalities)   [ Time Frame: From the first dose of study medication until 28 days after the last dose of study medication. However all AEs entered in the database from the treatment start were included in AE analyses ]

12.  Secondary:   Percentage of Participants With Treatment-emergent AEs (Treatment Related)   [ Time Frame: From the first dose of study medication until 28 days after the last dose of study medication. However all AEs entered in the database from the treatment start were included in AE analyses. ]

13.  Secondary:   Plasma Predose Concentration (Trough Concentration [Ctrough]) of Crizotinib and Its Metabolite   [ Time Frame: Cycle 2 Day 1, Cycle 3 Day 1 and Cycle 5 Day 1 ]

14.  Secondary:   Percentage of Participants for Each Anaplastic Lymphoma Kinase (ALK) Gene Fusion Variants   [ Time Frame: Screening ]

15.  Secondary:   ORR Between ALK Variant Groups Based on IRR   [ Time Frame: Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months) ]

16.  Secondary:   Time to Deterioration (TTD) in Pain in Chest, Dyspnea, or Cough   [ Time Frame: From Baseline to deterioration while on study treatment ]

17.  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)   [ Time Frame: Cycle 1 day 1 to end of treatment or withdrawal or crossover ]

18.  Secondary:   Change From Baseline Scores in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30   [ Time Frame: Cycle 1 day 1 to end of treatment or withdrawal or crossover ]

19.  Secondary:   Change From Baseline in Lung Cancer Symptom Scores as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13)   [ Time Frame: Cycle 1 day 1 to end of treatment or withdrawal or crossover ]

20.  Secondary:   Change From Baseline in General Health Status as Assessed by EuroQol 5D (EQ-5D)- Visual Analog Scale (VAS)   [ Time Frame: From Baseline up to treatment withdrawal or crossover ]

21.  Secondary:   Percentage of Participants With Hospital Admissions-Healthcare Resource Utilization (HCRU)   [ Time Frame: From 28 days prior to the start of study treatment and up to 28 days post the last dose of study treatment ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


No publications provided by Pfizer

Publications automatically indexed to this study:

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01154140     History of Changes
Other Study ID Numbers: A8081014, 2010-021336-33, XALCORI
Study First Received: June 29, 2010
Results First Received: November 26, 2014
Last Updated: March 20, 2015
Health Authority: United States: Food and Drug Administration