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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

NCT01491737

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: MO27775
  • SECONDARY ID: 2011-002132-10
  • NCT ID: NCT01491737

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
PertuzumabrhuMAb 2C4, Perjeta®Pertuzumab, Trastuzumab, AI or Induction Chemotherapy
TrastuzumabrhuMAb HER2, Herceptin®Pertuzumab, Trastuzumab, AI or Induction Chemotherapy
Aromatase InhibitorPertuzumab, Trastuzumab, AI or Induction Chemotherapy
Induction ChemotherapyPertuzumab, Trastuzumab, AI or Induction Chemotherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Pertuzumab, Trastuzumab, AI or Induction ChemotherapyExperimentalParticipants 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.
  • Pertuzumab
  • Trastuzumab
  • Aromatase Inhibitor
  • Induction Chemotherapy
Trastuzumab, AI or Induction ChemotherapyActive ComparatorParticipants 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.
  • Trastuzumab
  • Aromatase Inhibitor
  • Induction Chemotherapy

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS)
Time Frame:Baseline to progressive disease or death (approximately, up to 49 months)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:From the date of randomization until first documented death (approximately, up to 49 months)
Safety Issue:
Description: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.
Measure:Duration of Response (DOR)
Time Frame:Baseline up to 49 months, approximately
Safety Issue:
Description: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.
Measure:Time to Response (TTR)
Time Frame:Baseline up to 49 months, approximately
Safety Issue:
Description: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).
Measure:Objective Overall Response Rate (ORR)
Time Frame:Baseline up to 49 months, approximately
Safety Issue:
Description: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.
Measure:Clinical Benefit Response (CBR)
Time Frame:Baseline up to 49 months, approximately
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure:Percentage of Participants With Any Adverse Event (AE)
Time Frame:Up to 49 months approximately
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

November 6, 2017