ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01674062
Recruitment Status : Completed
First Posted : August 28, 2012
Results First Posted : September 11, 2015
Last Update Posted : August 22, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Pertuzumab Drug: Trastuzumab Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 95 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : May 2006
Actual Primary Completion Date : February 2008
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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 Name: 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 Name: 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 Name: 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 Name: Herceptin




Primary Outcome Measures :
  1. 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 [ Time Frame: 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) ]
    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.

  2. 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 [ Time Frame: 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) ]
    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.


Secondary Outcome Measures :
  1. 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 [ Time Frame: 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) ]
    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.

  2. 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 [ Time Frame: 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) ]
    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.

  3. Cohorts 1 and 2: Duration of Response According to RECIST Version 1.0 [ Time Frame: 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) ]
    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.

  4. Cohorts 1 and 2: Time to Objective Response According to RECIST Version 1.0 [ Time Frame: 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) ]
    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.

  5. Cohorts 1 and 2: Percentage of Participants With Disease Progression According to RECIST Version 1.0 [ Time Frame: 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) ]
    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.

  6. Cohorts 1 and 2: Time to Progression (TTP) According to RECIST Version 1.0 [ Time Frame: 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) ]
    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.

  7. Cohorts 1 and 2: Progression-Free Survival (PFS) According to RECIST Version 1.0 [ Time Frame: 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) ]
    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.

  8. Cohorts 1 and 2: Percentage of Participants Who Died [ Time Frame: 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) ]
    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.

  9. Cohorts 1 and 2: Overall Survival (OS) [ Time Frame: 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) ]
    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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01674062


Locations
Canada, Alberta
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, 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
Modena, Emilia-Romagna, Italy, 41100
Parma, Emilia-Romagna, Italy, 43100
Milano, Lombardia, Italy, 20133
Spain
Barcelona, Spain, 08003
Barcelona, Spain, 08035
Valencia, Spain, 46009
Valencia, Spain, 46010
United Kingdom
Edinburgh, United Kingdom, EH4 2XU
Manchester, United Kingdom, M20 4BX
Northwood, United Kingdom, HA6 2RN
Truro, United Kingdom, TR1 3LJ
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Chair: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01674062     History of Changes
Other Study ID Numbers: BO17929
2005-003493-19 ( EudraCT Number )
First Posted: August 28, 2012    Key Record Dates
Results First Posted: September 11, 2015
Last Update Posted: August 22, 2016
Last Verified: July 2016

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Pertuzumab
Trastuzumab
Antineoplastic Agents