Efficacy Trial Comparing ZD6474 With Erlotinib in NSCLC After Failure of at Least One Prior Chemotherapy

• ClinicalTrials.gov Identifier: NCT00364351
• Recruitment Status: Completed
• First Posted: August 15, 2006
• Results First Posted: May 24, 2011
• Last Update Posted: January 25, 2018
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

Tracking Information

• First Submitted Date: August 14, 2006
• First Posted Date: August 15, 2006
• Results First Submitted Date: April 27, 2011
• Results First Posted Date: May 24, 2011
• Last Update Posted Date: January 25, 2018
• Study Start Date: August 2006
• Actual Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 8, 2012)

Progression-Free Survival (PFS) [ Time Frame: progressionRECIST tumour assessments carried out every 4 weeks up to week 16 then every 8 weeks thereafter from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first, assessed. ]

Median time (in weeks) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable Response Evaluation Criteria In Solid Tumors (RECIST) assessment. Progression was derived according to RECIST 1.0 and is defined as an increase of at least 20% in the total tumour size of measurable lesions over the nadir measurement, unequivocal progression in the non-target lesions or the appearance of one or more new lesions.

• Original Primary Outcome Measures (submitted: August 14, 2006): Demonstrate an improvement in Progression Free Survival for ZD6474 compared with erlotinib in patients with locally advanced or metastatic NSCLC after failure of at least one but no more than two, prior chemotherapy regimes.

Current Secondary Outcome Measures (submitted: October 8, 2012)

• Overall Survival (OS) [ Time Frame: Time to death in months ]
  Overall survival is defined as the time from date of randomization until death. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie their status must be known at the censored date and should not be lost to follow up or unknown).
• Objective Response Rate (ORR) [ Time Frame: RECIST tumour assessments every 4 weeks up to week 16 then every 8 weeks thereafter from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first, assessed up to 21 months ]
  The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as determined according to RECIST 1.0. CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere and PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions.
• Disease Control Rate (DCR) [ Time Frame: RECIST tumour assessments carried out every 4 weeks until week 16 then every 8 weeks thereafter (+/- 3 days) from randomisation until objective progression ]
  Disease control rate is defined as the number of patients who achieved disease control at least 8 weeks following randomisation. Disease control is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 8 weeks as determined according to RECIST 1.0. CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere, PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions and SD >= 8 is assigned to patients who have not responded and have no evidence of progression at least 8 weeks after randomisation.
• Time to Deterioration of Disease-related Symptoms (TDS) by EORTC Quality of Life Questionnaire - Pain [ Time Frame: Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication), every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit ]
  Pain was assessed as the average score of two items: Question 9 ("Have you had pain") and 19 ("Did pain interfere with your daily activities") of the QLQ-C30. Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 28 days. A patient is defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 28 days.
• Time to Deterioration of Disease-related Symptoms (TDS) by EORTC Quality of Life Questionnaire - Dyspnoea [ Time Frame: Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication), every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit ]
  Dyspnea was assessed as the average score of four items: Question 8 of the QLQ-C30 ("Were you short of breath") and Question 3 of the QLQ-C30 ("Were you short of breath when you rested"), Questions 4 ("Were you short of breath when you walked") and 5 ("Were you short of breath when you climbed stairs") of the QLQ-LC13 (or, equivalently, Questions 33, 34 and 35 of the combined QLQ-C30 and QLQ-LC13 questionnaires). Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 28 days. A patient is defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 28 days.
• Time to Deterioration of Disease-related Symptoms (TDS) by EORTC Quality of Life Questionnaire - Cough [ Time Frame: Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication), every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit ]
  Cough was assessed using Question 1 ("How much did you cough") of the QLQ-LC13 (or, equivalently, Question 31 of the combined QLQ-C30 and QLQ-LC13 questionnaires). Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 28 days. A patient is defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 28 days.

• Original Secondary Outcome Measures (submitted: August 14, 2006): To demonstrate an overall improvement in survival for ZD6474 compared with erlotinib
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy Trial Comparing ZD6474 With Erlotinib in NSCLC After Failure of at Least One Prior Chemotherapy
• Official Title: A Phase III, International, Randomised, Double Blind, Parallel-Group Study to Assess the Efficacy of Zactima™ Versus Tarceva® in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Failure of at Least One Prior Chemotherapy
• Brief Summary: To determine if ZD6474 a new investigational drug, is effective in treating Non Small Lung Cancer and if so, how it compares with another type of anti cancer therapy chemotherapy, Erlotinib
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Non Small Cell Lung Cancer

Intervention

• Drug: Vandetanib
  once daily oral tablet
  Other Names:

  • ZD6474
  • ZACTIMA™
• Drug: Erlotinib
  oral dose
  Other Name: Tarceva®

Study Arms

• Active Comparator: 1
  Erlotinib
  Intervention: Drug: Erlotinib
• Experimental: 2
  Vandetanib
  Intervention: Drug: Vandetanib

Publications *

• Natale RB, Thongprasert S, Greco FA, Thomas M, Tsai CM, Sunpaweravong P, Ferry D, Mulatero C, Whorf R, Thompson J, Barlesi F, Langmuir P, Gogov S, Rowbottom JA, Goss GD. Phase III trial of vandetanib compared with erlotinib in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol. 2011 Mar 10;29(8):1059-66. doi: 10.1200/JCO.2010.28.5981. Epub 2011 Jan 31.
• Platt A, Morten J, Ji Q, Elvin P, Womack C, Su X, Donald E, Gray N, Read J, Bigley G, Blockley L, Cresswell C, Dale A, Davies A, Zhang T, Fan S, Fu H, Gladwin A, Harrod G, Stevens J, Williams V, Ye Q, Zheng L, de Boer R, Herbst RS, Lee JS, Vasselli J. A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies. BMC Cancer. 2015 Mar 23;15:171. doi: 10.1186/s12885-015-1146-8.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 17, 2014): 1574
• Original Enrollment (submitted: August 14, 2006): 1150
• Actual Study Completion Date: November 2016
• Actual Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Confirmed locally advanced or metastatic NSCLC
• Failure of at least one but not more than two prior chemotherapy regimens

Exclusion Criteria:

• Prior treatment with erlotinib (Tarceva), gefitinib (IRESSA), sunitinib (Sutent), sorafenib (Nexavar)
• Chemotherapy or other type of anti cancer therapy within 4 weeks of study start

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Brazil, Canada, China, Denmark, France, Germany, Hong Kong, India, Indonesia, Italy, Korea, Republic of, Mexico, Netherlands, Norway, Philippines, Spain, Taiwan, Thailand, United Kingdom, United States
• Removed Location Countries: Sweden

Administrative Information

• NCT Number: NCT00364351
• Other Study ID Numbers: D4200C00057; EUDRACT No. 2006-000259-16
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
• Original Responsible Party: Not Provided
• Current Study Sponsor: Genzyme, a Sanofi Company
• Original Study Sponsor: AstraZeneca
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: January 2018