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Trial record 1 of 1 for:    NCT01026142
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A Study of a Combination of Trastuzumab and Capecitabine With or Without Pertuzumab in Patients With HER2-positive Metastatic Breast Cancer (PHEREXA)

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ClinicalTrials.gov Identifier: NCT01026142
Recruitment Status : Completed
First Posted : December 4, 2009
Results First Posted : October 13, 2016
Last Update Posted : August 14, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE November 27, 2009
First Posted Date  ICMJE December 4, 2009
Results First Submitted Date  ICMJE August 17, 2016
Results First Posted Date  ICMJE October 13, 2016
Last Update Posted Date August 14, 2018
Actual Study Start Date  ICMJE January 26, 2010
Actual Primary Completion Date May 29, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 1, 2017)
Progression Free Survival (Independent Assessment) [ Time Frame: Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years). ]
Progression Free Survival (PFS) was defined as the time from randomization to first documented disease progression (PD), as determined by an Independent Review Facility (IRF) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. IRF review of tumor assessment ceased after the primary PFS analysis. The primary endpoint was analyzed after approximately 337 IRF-assessed PFS events were observed.
Original Primary Outcome Measures  ICMJE
 (submitted: December 3, 2009)
Progression Free Survival (Independent Assessment) [ Time Frame: Tumor Assessment every 9 weeks until week 27, then every 12 weeks thereafter ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2018)
  • Overall Survival (OS) [ Time Frame: From randomization until death from any cause (up to 7.5 years). ]
    Overall Survival (OS) was defined as the time from the date of randomization to the date of death from any cause. The results of the final OS analysis are presented here. Participants who were alive or lost to follow-up at the time of the analysis were censored at the last known alive date. Participants with no postbaseline information were censored at the time of randomization plus 1 day. Prior to the final data analysis cut-off, it was ensured that all participants who were in survival follow-up had been contacted as recently as possible within the last 3 months to confirm current survival status.
  • Overall Survival (OS) Rate Based on a 2-year Truncated Analysis [ Time Frame: From randomization until death from any cause (up to 2 years) ]
    The Overall Survival (OS) 2-year truncated analysis is the Kaplan-Meier estimate of the percentage of participants who were surviving at 2 years. OS is defined as the time from the date of randomization to the date of death from any cause, with censoring of all events and follow-up beyond the end of the second year.
  • Investigator Assessment Progression-Free Survival (PFS) [ Time Frame: Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 7.5 years). ]
    Investigator Assessment Progression-Free Survival (PFS) was defined as the time from randomization to the first documented progressive disease, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.0, or death from any cause, whichever occurred first. PD is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
  • Time to Progression (TTP) Based Upon Independent Review Facility (IRF) Assessment [ Time Frame: Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years). ]
    Time to Progression (TTP) was defined as time between randomization and the first occurrence of progressive disease (PD), based on IRF assessment.
  • Time to Treatment Failure (TTF) Based Upon Independent Review Facility (IRF) Assessment [ Time Frame: Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years). ]
    Time to Treatment Failure (TTF) was defined as time between randomization and date of disease progression based on independent review, death, or withdrawal of treatment due to adverse events, withdrawn informed consent, refusal of treatment/failure to cooperate, or failure to return, whichever occurred first.
  • Overall Objective Response Rate (ORR) [ Time Frame: Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years). ]
    Overall Objective Response Rate is based upon investigator and IRF assessments. Objective Response Rate (ORR) was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) among those who had measurable disease at baseline. CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
  • Clinical Benefit Rate (CBR) [ Time Frame: Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years). ]
    Clinical Benefit Rate is based upon Independent Review Facility (IRF) assessments; defined as the percentage of participants a complete response (CR), partial response (PR), or stable disease for at least 8 cycles or 6 months.
  • Duration of Objective Response [ Time Frame: Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years). ]
    Duration of Objective Response was defined for the subpopulation of responders as time from first Independent Review Facility (IRF)-assessed complete response (CR) or partial response (PR) to subsequent first documented, IRF-confirmed evidence of disease progression. Only participants with an objective response were included in the analysis of duration of objective response.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 3, 2009)
  • Progression free survival (investigator assessment) [ Time Frame: Tumor Assessment every 9 weeks until week 27, then every 12 weeks thereafter ]
  • Time to progression [ Time Frame: Tumor Assessment every 9 weeks until week 27, then every 12 weeks thereafter ]
  • Time to treatment failure [ Time Frame: Tumor Assessment every 9 weeks until week 27, then every 12 weeks thereafter ]
  • Overall objective response [ Time Frame: Tumor Assessment every 9 weeks until week 27, then every 12 weeks thereafter ]
  • Clinical benefit rate [ Time Frame: Tumor Assessment every 9 weeks until week 27, then every 12 weeks thereafter ]
  • Duration of response [ Time Frame: Tumor Assessment every 9 weeks until week 27, then every 12 weeks thereafter ]
  • Safety, Tolerability; AEs, laboratory parameters [ Time Frame: AEs: throughout study, laboratory assessments: every 3 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of a Combination of Trastuzumab and Capecitabine With or Without Pertuzumab in Patients With HER2-positive Metastatic Breast Cancer (PHEREXA)
Official Title  ICMJE A Multicenter Randomized Phase III Study to Compare the Combination Trastuzumab and Capecitabine, With or Without Pertuzumab, in Patients With HER2-Positive Metastatic Breast Cancer That Have Progressed After One Line of Trastuzumab-Based Therapy in the Metastatic Setting (PHEREXA)
Brief Summary This randomized, two-arm study evaluated the efficacy and safety of a combination of trastuzumab and capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The study population consisted of female patients, whose disease had progressed during or following previous trastuzumab therapy for metastatic disease. All patients in Arm A and Arm B received trastuzumab (8 mg/kg iv as loading dose and then 6 mg/kg iv every 3 weeks thereafter) and capecitabine oral twice daily for 14 days every 3 weeks (1250 mg/m2 twice daily in Arm A and 1000 mg/m2 twice daily in Arm B). In addition, patients in Arm B received pertuzumab (840 mg iv as loading dose and then 420 mg iv thereafter) every 3 weeks. Study treatment continued until disease progression or unacceptable toxicity.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Capecitabine
    1000 mg/m2 po twice daily for 14 days every 3 weeks
    Other Name: Xeloda
  • Drug: Capecitabine
    1250 mg/m2 po twice daily for 14 days every 3 weeks
    Other Name: Xeloda
  • Drug: Pertuzumab
    840 mg iv loading, then 420 mg iv every 3 weeks
    Other Name: Perjeta
  • Drug: Trastuzumab
    8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks
    Other Name: Herceptin
Study Arms  ICMJE
  • Active Comparator: A: Capecitabine + Trastuzumab
    Interventions:
    • Drug: Capecitabine
    • Drug: Trastuzumab
  • Experimental: B: Capecitabine + Trastuzumab + Pertuzumab
    Interventions:
    • Drug: Capecitabine
    • Drug: Pertuzumab
    • Drug: Trastuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 6, 2014)
452
Original Estimated Enrollment  ICMJE
 (submitted: December 3, 2009)
450
Actual Study Completion Date  ICMJE August 7, 2017
Actual Primary Completion Date May 29, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult female patients >/=18 years of age
  • Metastatic HER2 positive breast cancer
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Disease progression during or following trastuzumab-based therapy for 1st line metastatic breast cancer (trastuzumab must have been part of the last prior treatment regimen)
  • Prior treatment with taxane-containing regimen
  • Left ventricular ejection fraction (LVEF) >/=50 percent
  • For women of childbearing potential agreement to use highly effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by patient and/or partner. Contraception must continue for duration of study treatment and for at least 6 months after last dose of study drug treatment

Exclusion Criteria:

  • Prior treatment with pertuzumab or capecitabine
  • Concurrent treatment with other experimental drug
  • Concurrent immunotherapy or anticancer hormonal therapy
  • Serious concurrent disease (e.g. active infection, uncontrolled hypertension, cardiovascular disease)
  • Central nervous system (CNS) metastases, which are not well controlled
  • History of exposure to anthracycline cumulative dose equivalent to 360mg/m2
  • History of congestive heart failure of any New York Heart Association criteria, or serious cardiac arrhythmia requiring treatment
  • History of myocardial infarction within 6 months prior to randomization
  • History of LVEF decline to below 50% during or after prior trastuzumab therapy or other cardiac toxicity during previous trastuzumab treatment that necessitated discontinuation of trastuzumab
  • History of another cancer which could affect compliance or result interpretation
  • Inadequate organ function
  • Pregnant or breastfeeding women
  • life expectancy < 12 weeks
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Austria,   Belgium,   Brazil,   Canada,   Croatia,   Czechia,   Estonia,   France,   Germany,   Hong Kong,   Hungary,   Italy,   Korea, Republic of,   Mexico,   Netherlands,   Peru,   Poland,   Romania,   Russian Federation,   Spain,   Thailand,   United Kingdom
Removed Location Countries Czech Republic,   Lithuania,   Slovakia,   Switzerland
 
Administrative Information
NCT Number  ICMJE NCT01026142
Other Study ID Numbers  ICMJE MO22324
2008-006801-17 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP