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A Study of Pertuzumab in Combination With Trastuzumab Plus an Aromatase Inhibitor in Participants With Metastatic Human Epidermal Growth Factor Receptor 2 (HER2)-Positive and Hormone Receptor-Positive Advanced Breast Cancer (PERTAIN)

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ClinicalTrials.gov Identifier: NCT01491737
Recruitment Status : Active, not recruiting
First Posted : December 14, 2011
Results First Posted : June 7, 2017
Last Update Posted : November 7, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE December 6, 2011
First Posted Date  ICMJE December 14, 2011
Results First Submitted Date  ICMJE May 11, 2017
Results First Posted Date  ICMJE June 7, 2017
Last Update Posted Date November 7, 2019
Actual Study Start Date  ICMJE February 17, 2012
Actual Primary Completion Date March 17, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 11, 2017)
Progression-Free Survival (PFS) [ Time Frame: Baseline to progressive disease or death (approximately, up to 49 months) ]
PFS is defined as the time from randomization until the first radiographically documented progression of disease or death from any cause, whichever occurred first (either during study treatment or during follow-up). Progression of disease was evaluated according to the response evaluation criteria in solid tumors (RECIST) (version 1.1). Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (Note: the appearance of one or more new lesions is also considered progression). Participants with no PFS events were censored at the time of the last evaluable tumor assessment.
Original Primary Outcome Measures  ICMJE
 (submitted: December 12, 2011)
Progression-free Survival [ Time Frame: Up to approximately 49 months ]
Change History Complete list of historical versions of study NCT01491737 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 11, 2017)
  • Overall Survival (OS) [ Time Frame: From the date of randomization until first documented death (approximately, up to 49 months) ]
    OS is defined as the time from the date of randomization to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication (pertuzumab, trastuzumab, AI or induction chemotherapy), and participants with no post-baseline information were censored at the date of randomization.
  • Duration of Response (DOR) [ Time Frame: Baseline up to 49 months, approximately ]
    DOR was defined as the period from the date of initial confirmed partial response (PR) or complete response (CR) until the date of progressive disease or death from any cause. According to RECIST version 1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants with no documented progression after CR or PR were censored at the last date at which they were known to have had the CR or PR, respectively.
  • Time to Response (TTR) [ Time Frame: Baseline up to 49 months, approximately ]
    TTR was defined as the time from the date of randomization to the date of first CR or PR. According to RECIST version 1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. A censored time to response was calculated at the date of the last adequate tumor assessment as there was no date of confirmed response (CR or PR). If no tumor assessment is performed for the participant (or all post-baseline assessments are not evaluable or PD) the censoring day would be set to day 1 (date of randomization).
  • Objective Overall Response Rate (ORR) [ Time Frame: Baseline up to 49 months, approximately ]
    ORR was defined as participants with best (confirmed) overall response (BOR) of either CR or PR. ORR was assessed by the investigator according to RECIST version 1.1 and is based on BOR, which is defined as best response recorded from start of study treatment until disease progression/recurrence or death. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference baseline sum diameters; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Participants needed to have two consecutive assessments of PR or CR to be a responder. Only participants with measurable disease at baseline were included in the analysis of BOR and who did not have any evaluable post-baseline assessments were classified as not evaluable.
  • Clinical Benefit Response (CBR) [ Time Frame: Baseline up to 49 months, approximately ]
    CBR is percentage of participants with best (confirmed) PR or CR or SD for at least 6 months. According to RECIST version 1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
  • Change From Baseline in Health-Related Quality of Life as Determined by European Quality of Life 5-Dimension (EQ-5D) Visual Analog Scale (VAS) Scores [ Time Frame: Baseline, every 3 cycles (21-day cycle), and every 3 months after treatment discontinuation (up to 49 months, approximately) ]
    EQ-5D VAS: participant rated questionnaire to assess health-related quality of life (QoL) in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state.
  • Percentage of Participants With Any Adverse Event (AE) [ Time Frame: Up to 49 months approximately ]
    An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 12, 2011)
  • Overall Survival [ Time Frame: Up to approximately 49 months ]
  • Overall Response Rate [ Time Frame: Up to approximately 49 months ]
  • Clinical Benefit Rate [ Time Frame: Up to approximately 49 months ]
  • Duration of Response [ Time Frame: Up to approximately 49 months ]
  • Time to Response [ Time Frame: Up to approximately 49 months ]
  • Safety: Incidence of Adverse Events [ Time Frame: Up to approximately 49 months ]
  • Quality of Life: EQ-5D Questionnaire [ Time Frame: Up to approximately 49 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Pertuzumab in Combination With Trastuzumab Plus an Aromatase Inhibitor in Participants With Metastatic Human Epidermal Growth Factor Receptor 2 (HER2)-Positive and Hormone Receptor-Positive Advanced Breast Cancer
Official Title  ICMJE A Randomized, Two-Arm, Open-Label, Multicenter Phase II Trial Assessing the Efficacy and Safety of Pertuzumab Given in Combination With Trastuzumab Plus an Aromatase Inhibitor in First Line Patients With HER2-Positive and Hormone Receptor-Positive Advanced (Metastatic or Locally Advanced) Breast Cancer
Brief Summary This randomized, open-label, two-arm, multi-center, Phase II study will evaluate the efficacy and safety of pertuzumab in combination with trastuzumab plus an aromatase inhibitor (AI) in first-line participants with HER2-positive and hormone receptor-positive advanced breast cancer. Participants will be randomized to one of two treatment arms; Arm A (pertuzumab in combination with trastuzumab plus an AI) or Arm B (trastuzumab plus an AI). Participants may also receive induction chemotherapy (a taxane, either docetaxel or paclitaxel) at the investigator's discretion in combination with the assigned treatment arm. The anticipated time on study treatment is until disease progression, unacceptable toxicity, withdrawal of consent, or death whichever occurs first.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Pertuzumab
    Participants will receive a loading dose of 840 milligrams (mg) as an intravenous infusion on Day 1 of first treatment cycle, followed by 420 mg on Day 1 or Day 2 of each subsequent 3-week cycle until disease progression or unacceptable toxicity.
    Other Name: rhuMAb 2C4, Perjeta®
  • Drug: Trastuzumab
    Participants will receive a loading dose of 8 milligrams per kilogram (mg/kg) as an intravenous infusion on Day 1 or 2 of first treatment cycle, followed by 6 mg/kg on Day 1 or Day 2 of each subsequent treatment 3-week cycles until disease progression or unacceptable toxicity.
    Other Name: rhuMAb HER2, Herceptin®
  • Drug: Aromatase Inhibitor
    Participants will receive 1 mg anastrozole or 2.5 mg letrozole orally once daily.
  • Drug: Induction Chemotherapy
    Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period will receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective pertuzumab and/or trastuzumab infusions at the investigator's discretion.
Study Arms  ICMJE
  • Experimental: Pertuzumab, Trastuzumab, AI or Induction Chemotherapy

    Participants will receive pertuzumab in combination with trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

    Participants may also receive induction chemotherapy (docetaxel every 3 weeks or paclitaxel weekly) up to the first 18-24 weeks of the treatment period at the investigator's discretion.

    Interventions:
    • Drug: Pertuzumab
    • Drug: Trastuzumab
    • Drug: Aromatase Inhibitor
    • Drug: Induction Chemotherapy
  • Active Comparator: Trastuzumab, AI or Induction Chemotherapy

    Participants will receive trastuzumab plus AI until predefined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

    Participants may also receive induction chemotherapy (docetaxel every 3 weeks or paclitaxel weekly) up to the first 18-24 weeks of the treatment period at the investigator's discretion.

    Interventions:
    • Drug: Trastuzumab
    • Drug: Aromatase Inhibitor
    • Drug: Induction Chemotherapy
Publications * Rimawi M, Ferrero JM, de la Haba-Rodriguez J, Poole C, De Placido S, Osborne CK, Hegg R, Easton V, Wohlfarth C, Arpino G; PERTAIN Study Group. First-Line Trastuzumab Plus an Aromatase Inhibitor, With or Without Pertuzumab, in Human Epidermal Growth Factor Receptor 2-Positive and Hormone Receptor-Positive Metastatic or Locally Advanced Breast Cancer (PERTAIN): A Randomized, Open-Label Phase II Trial. J Clin Oncol. 2018 Oct 1;36(28):2826-2835. doi: 10.1200/JCO.2017.76.7863. Epub 2018 Aug 14.

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 4, 2017)
258
Original Estimated Enrollment  ICMJE
 (submitted: December 12, 2011)
250
Estimated Study Completion Date  ICMJE November 1, 2019
Actual Primary Completion Date March 17, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants with HER2-positive and hormone receptor-positive advanced metastatic or locally advanced breast cancer
  • Post-menopausal status over 1 year
  • HER2-positive as assessed by local laboratory on primary or metastatic tumor
  • Hormone-receptor positive defined as estrogen receptor-positive and/or progesterone receptor-positive
  • At least one measurable lesion and/or non-measurable disease evaluable according to Response Evaluation Criteria In Solid Tumors Version 1.1

Exclusion Criteria:

  • Previous systemic non-hormonal anticancer therapy in the metastatic or locally advanced breast cancer setting
  • Previous treatment with anti-HER2 agents for breast cancer, except trastuzumab and/or lapatinib in the neoadjuvant or adjuvant setting
  • Disease progression while receiving adjuvant trastuzumab and/or lapatinib treatment
  • History of persistent Grade 2 or higher hematological toxicity according to National Cancer Institute-Common Toxicity Criteria Version 4.0
  • Disease-free interval from completion of adjuvant/neo-adjuvant systemic non-hormonal treatment to recurrence of within 6 months
  • Other malignancies within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma
  • Clinical or radiographic evidence of central nervous system metastases or significant cardiovascular disease
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 Brazil,   France,   India,   Italy,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01491737
Other Study ID Numbers  ICMJE MO27775
2011-002132-10 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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 October 2019

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