A Study of Perjeta (Pertuzumab) in Combination With Herceptin (Trastuzumab) in Participants With Metastatic Breast Cancer

An Exploratory Phase II, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of the Combination of Pertuzumab and Herceptin (Trastuzumab) in Patients With HER2-Positive Metastatic Breast Cancer

This study will evaluate the efficacy and safety of Perjeta (pertuzumab) in combination with Herceptin (trastuzumab) in participants with metastatic breast cancer who have progressed on trastuzumab-based therapy (Cohorts 1 and 2), and will make a preliminary assessment of the efficacy and safety of single-agent pertuzumab (Cohort 3). Objective response rate and clinical benefit will be assessed. Pertuzumab will be administered at an initial dose of 840 milligrams (mg) intravenously (IV) on Day 1, followed by 420 mg IV every 3 weeks. Trastuzumab will be administered at the same schedule the participant was following before entry into the study. An additional cohort of participants at certain centers will receive pertuzumab monotherapy at an initial dose of 840 mg IV on Day 1, followed by 420 mg IV every 3 weeks. These participants may have trastuzumab added to the regimen in the event of progression during single-agent pertuzumab treatment.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Pertuzumab; Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
  • Ontario
    • London, Ontario, Canada, N6A 4L6
    • Ottawa, Ontario, Canada, K1H 8L6
    • Toronto, Ontario, Canada, M4N 3M5
• France
  • Besancon, France, 25030
  • Dijon, France, 21079
  • Lille, France, 59020
  • Montpellier, France, 34298
• Italy
  • Emilia-Romagna
    • Modena, Emilia-Romagna, Italy, 41100
    • Parma, Emilia-Romagna, Italy, 43100
  • Lombardia
    • Milano, Lombardia, Italy, 20133
• Spain
  • Barcelona, Spain, 08003
  • Barcelona, Spain, 08035
  • Valencia, Spain, 46010
  • Valencia, Spain, 46009
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
  • Manchester, United Kingdom, M20 4BX
  • Northwood, United Kingdom, HA6 2RN
  • Truro, United Kingdom, TR1 3LJ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Females greater than or equal to (≥) 18 years of age, with histologically-confirmed HER2-positive breast cancer
• Metastatic breast cancer, with progression on trastuzumab-based therapy as last treatment for metastatic disease
• Less than or equal to (≤) 3 chemotherapy regimens prior to study entry
• Last trastuzumab dose ≤9 weeks before study entry for participants receiving pertuzumab + trastuzumab, and ≥4 weeks for participants receiving pertuzumab monotherapy
• Left ventricular ejection fraction ≥55% at study entry

Exclusion Criteria:

• Previous treatment with an anti-cancer vaccine or any targeted therapy other than trastuzumab
• Brain metastases
• History of any cardiac adverse event related to trastuzumab therapy
• Any other malignancy in the last 5 years, except for basal cell cancer or cancer in situ of the cervix

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pertuzumab + Trastuzumab (Cohorts 1 and 2); Females with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer will receive dual-agent treatment with pertuzumab and trastuzumab. Trastuzumab will be administered IV as 2 milligrams per kilogram (mg/kg) once weekly, or as 6 mg/kg every 3 weeks, beginning on Day 1 of Cycle 1. Pertuzumab will be administered IV at a loading dose of 840 mg followed by a standard dose of 420 mg every 3 weeks, beginning on Day 2 of Cycle 1. Thereafter, both medications will be administered on Day 1 of each 3-week cycle. Treatment will continue for a minimum of 8 cycles and may be extended until disease progression, intolerable toxicity, or death.	Drug: Pertuzumab; Loading dose 840 mg IV on Day 2 of Cycle 1, followed by 420 mg every 3 weeks thereafter, until disease progression or unacceptable toxicity.; Other Names: Perjeta; Drug: Trastuzumab; 2 mg/kg IV once weekly, or as 6 mg/kg every 3 weeks, beginning on Day 1 of Cycle 1 and on Day 1 of each 3-week cycle thereafter until disease progression or unacceptable toxicity.; Other Names: Herceptin
Experimental: Pertuzumab +/- Trastuzumab (Cohort 3); Females with HER2-positive metastatic breast cancer will receive single-agent treatment with pertuzumab. Pertuzumab will be administered IV at a loading dose of 840 mg followed by a standard dose of 420 mg every 3 weeks, administered on Day 1 of each 3-week cycle. Participants with documented disease progression may have trastuzumab added to the regimen, per the dosing schedule described for Cohorts 1 and 2, to receive dual-agent treatment until disease progression, intolerable toxicity, or death.	Drug: Pertuzumab; Loading dose 840 mg IV on Day 2 of Cycle 1, followed by 420 mg every 3 weeks thereafter, until disease progression or unacceptable toxicity.; Other Names: Perjeta; Drug: Trastuzumab; 2 mg/kg IV once weekly, or as 6 mg/kg every 3 weeks, beginning on Day 1 of Cycle 1 and on Day 1 of each 3-week cycle thereafter until disease progression or unacceptable toxicity.; Other Names: Herceptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohorts 1 and 2: Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 During Dual-Agent Treatment	Tumor response was assessed using RECIST version 1.0 to determine the objective response (OR) rate, or the percentage of participants with either confirmed CR or PR. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30 percent (%) decrease in the sum of the longest diameter compared to Baseline. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The OR rate was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100.	Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Cohorts 1 and 2: Percentage of Participants With a Confirmed Best Overall Response of CR, PR, or Stable Disease (SD) According to RECIST Version 1.0 During Dual-Agent Treatment	Tumor response was assessed using RECIST version 1.0 to determine the clinical benefit response (CBR) rate, or the percentage of participants with either confirmed CR or PR, or SD lasting at least 6 months. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient (20%) increase to qualify for disease progression, in addition to no new target lesions. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The CBR rate was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100.	Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 3: Percentage of Participants With a Confirmed Best Overall Response of CR or PR According to RECIST Version 1.0 During Single-Agent Treatment With Pertuzumab	Tumor response was assessed using RECIST version 1.0 to determine the OR rate, or the percentage of participants with either confirmed CR or PR. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The OR rate was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100.	Up to approximately 7.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Cohort 3: Percentage of Participants With a Confirmed Best Overall Response of CR, PR, or SD According to RECIST Version 1.0 During Single-Agent Treatment With Pertuzumab	Tumor response was assessed using RECIST version 1.0 to determine the CBR rate, or the percentage of participants with either confirmed CR or PR, or SD lasting at least 6 months. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient (20%) increase to qualify for disease progression, in addition to no new target lesions. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The CBR rate was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100.	Up to approximately 7.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Cohorts 1 and 2: Duration of Response According to RECIST Version 1.0	Tumor response was assessed using RECIST version 1.0 to determine OR and CBR rates. Duration of OR was defined as time from initial response of CR or PR to time of disease progression or death. Duration of CBR was defined similarly as time from initial response of CR or PR, or SD lasting at least 6 months, to time of disease progression or death. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient (20%) increase to qualify for disease progression, in addition to no new target lesions. Participants without progression or death following confirmed CR or PR were censored at the last tumor assessment. Duration of response was estimated using Kaplan-Meier analysis and expressed in weeks.	Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Cohorts 1 and 2: Time to Objective Response According to RECIST Version 1.0	Tumor response was assessed using RECIST version 1.0 to determine the OR rate. Time to response was defined as the time from first dose to the time of initial response of CR or PR. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. Participants with disease progression were censored at the time of progression, and those with neither disease progression nor OR were censored at the last tumor assessment. Time to response was estimated using Kaplan-Meier analysis and expressed in weeks.	Up to approximately 21 months (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression; final analysis using February 2008 cutoff date)
Cohorts 1 and 2: Percentage of Participants With Disease Progression According to RECIST Version 1.0	Tumor response was assessed using RECIST version 1.0 to assess for disease progression, defined as at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions. The percentage of participants with disease progression was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100.	Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Cohorts 1 and 2: Time to Progression (TTP) According to RECIST Version 1.0	Tumor response was assessed using RECIST version 1.0 to assess for disease progression, defined as at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions. TTP was defined as the time from first dose to the time of first documented disease progression. Participants who withdrew from the study without documented progression were censored at the last tumor assessment. TTP was estimated using Kaplan-Meier analysis and expressed in weeks.	Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Cohorts 1 and 2: Progression-Free Survival (PFS) According to RECIST Version 1.0	Tumor response was assessed using RECIST version 1.0 to assess for disease progression, defined as at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions. PFS was defined as the time from first dose to the time of disease progression or death. Participants without progression or death were censored at the last tumor assessment. PFS was estimated using Kaplan-Meier analysis and expressed in weeks.	Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Cohorts 1 and 2: Percentage of Participants Who Died	Participants were followed for survival data during and after treatment for a maximum of 3 years after the last dose until death, withdrawal of consent, or loss to follow-up. The percentage of participants who died was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.	Up to approximately 4.5 years (during treatment; then every 4 months until death, withdrawn consent, loss to follow-up, or 3 years after last dose; final analysis using November 2010 cutoff date)
Cohorts 1 and 2: Overall Survival (OS)	Participants were followed for survival data during and after treatment for a maximum of 3 years after the last dose until death, withdrawal of consent, or loss to follow-up. OS was defined as the time from first dose to the time of death from any cause. Participants who did not experience death were censored at the last known alive date. OS was estimated using Kaplan-Meier and expressed in months.	Up to approximately 4.5 years (during treatment; then every 4 months until death, withdrawn consent, loss to follow-up, or 3 years after last dose; final analysis using November 2010 cutoff date)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: August 24, 2012
• First Submitted That Met QC Criteria: August 24, 2012
• First Posted (Estimate): August 28, 2012

Study Record Updates

• Last Update Posted (Estimate): August 22, 2016
• Last Update Submitted That Met QC Criteria: July 20, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab; Pertuzumab
• Other Study ID Numbers: BO17929; 2005-003493-19 (EudraCT Number)