Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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: August 17, 2016
Last verified: August 2016
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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 Assessment every 9 weeks until week 27, then every 12 weeks thereafter ] [ Designated as safety issue: No ]
    Progression Free Survival is defined as the time from randomization to the first documented disease progression, (PD) as determined by IRF using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, or death from any cause, whichever occurs first.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: From randomization until death from any cause ] [ Designated as safety issue: No ]
    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 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 patients have died (approximately 300 deaths). Analysis methods at this time will be the same as those described for the primary endpoint. Prior to the data analysis cut-off, it will be ensured that all patients 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) Based on a 2-year Truncated Analysis [ Time Frame: From randomization until death from any cause ] [ Designated as safety issue: No ]
    Overall Survival 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 Assessment every 9 weeks until week 27, then every 12 weeks thereafter ] [ Designated as safety issue: No ]
    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.

  • Time to Progression (TTP) Based Upon Independent Review Facility (IRF) Assessment [ Time Frame: Tumor Assessment every 9 weeks until week 27, then every 12 weeks thereafter ] [ Designated as safety issue: No ]
    Time to Progression (TTP) was defined as time between randomization and the first occurrence of progressive disease.

  • Time to Treatment Failure (TTF) [ Time Frame: Tumor Assessment every 9 weeks until week 27, then every 12 weeks thereafter ] [ Designated as safety issue: No ]
    Time to Treatment Failure (TTF) was defined as time between randomization and date of disease progression based on IRF assessments, 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. Based upon Independent Review Facility (IRF) assessment.

  • Overall Objective Response Rate (ORR) [ Time Frame: Tumor Assessment every 9 weeks until week 27, then every 12 weeks thereafter ] [ Designated as safety issue: No ]
    Overall Objective Response Rate is based upon investigator and Independent Review Facility (IRF) assessments. Objective Response Rate (ORR) was defined as the percentage of patients with a confirmed complete response (CR) or partial response (PR) among those who had measurable disease at baseline. Patients without a post-baseline tumor assessment were considered to be non-responders.

  • Clinical Benefit Rate (CBR) [ Time Frame: Tumor Assessment every 9 weeks until week 27, then every 12 weeks thereafter ] [ Designated as safety issue: No ]
    Clinical Benefit Rate is based upon Independent Review Facility (IRF) assessments; defined as the percentage of patients with 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 Assessment every 9 weeks until week 27, then every 12 weeks thereafter ] [ Designated as safety issue: No ]
    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 patients with an objective response were included in the analysis of duration of objective response.


Enrollment: 452
Study Start Date: January 2010
Estimated Study Completion Date: October 2018
Primary Completion Date: May 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)
Genders 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 185 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: August 17, 2016
Health Authority: Austria: Federal Agency for Safety in Health Care, Vienna

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 December 07, 2016