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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)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01026142
First received: November 27, 2009
Last updated: May 2, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Breast Cancer Drug: capecitabine [Xeloda] Drug: pertuzumab Drug: trastuzumab [Herceptin] Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: From randomization until death from any cause, estimated to occur within 21 months after last patient randomized. This interim analysis data cut-off was 5.5 years. ]
    Overall Survival (OS) was defined as the time from the date of randomization to the date of death from any cause. An interim analysis of OS (when approximately 200 deaths had occurred) was performed at the time of the analysis of the primary endpoint, Independent Review Facility (IRF)-assessed Progression-Free Survival (PFS), with type 1 error control. The final OS analysis will take place at the end of study when 67% of participants have died (approximately 300 deaths). Prior to the final data analysis cut-off, it will be ensured that all participants who are in survival follow-up have 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) rate is the percentage of participants who were surviving at the 2-year analysis. 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 5.5 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, 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) 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). ]
    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.


Enrollment: 452
Actual Study Start Date: January 31, 2010
Estimated Study Completion Date: October 31, 2018
Primary Completion Date: May 31, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A Drug: capecitabine [Xeloda]
1250 mg/m2 po twice daily for 14 days every 3 weeks
Drug: trastuzumab [Herceptin]
8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks
Experimental: B Drug: capecitabine [Xeloda]
1000 mg/m2 po twice daily for 14 days every 3 weeks
Drug: pertuzumab
840 mg iv loading, then 420 mg iv every 3 weeks
Drug: trastuzumab [Herceptin]
8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01026142

  Show 191 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01026142     History of Changes
Other Study ID Numbers: MO22324
2008-006801-17
Study First Received: November 27, 2009
Results First Received: August 17, 2016
Last Updated: May 2, 2017

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Capecitabine
Pertuzumab
Trastuzumab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 21, 2017