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

Breast Cancer Clinical Trial

Official title:

An Exploratory Single-arm Study to Evaluate the Effect of Pertuzumab in Combination With Herceptin on Response Rate in Patients With HER2-positive Metastatic Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01674062
• Other study ID #: BO17929
• Secondary ID: 2005-003493-19
• Status: Active, not recruiting
• Phase: Phase 2
• First received: August 24, 2012
• Last updated: September 24, 2015
• Start date: May 2006
• Est. completion date: December 2017

Study information

• Verified date: September 2015
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy and safety of Perjeta (pertuzumab) in combination with Herceptin in patients with metastatic breast cancer who have progressed on Herceptin-based therapy, and will make a preliminary assessment of the efficacy and safety of single agent pertuzumab. Objective response rate and clinical benefit will be assessed. Pertuzumab will be administered at an initial dose of 840mg intravenously (iv) on day 1, followed by 420mg iv every 3 weeks. Herceptin will be administered at the same schedule the patient was following before entry into the study. An additional cohort of patients, at certain centers, will receive pertuzumab monotherapy, at an initial dose of 840mg iv on day 1, followed by 420mg iv every 3 weeks. The anticipated time on study treatment is until disease progression.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 95
• Est. completion date: December 2017
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients, >=18 years of age, with histologically-confirmed HER2-positive breast cancer

• Metastatic breast cancer, with progression on Herceptin-based therapy as last treatment for metastatic disease

• <=3 chemotherapy regimens prior to study entry

• Last Herceptin dose <=9 weeks before study entry for patients reciving pertuzumab + Herceptin, and >=4 weeks for patients receiving pertuzumab monotherapy

• LVEF>= 55% at study entry

Exclusion Criteria:

• Previous treatment with an anti-cancer vaccine or any targeted therapy other than Herceptin

• Brain metastases

• History of any cardiac AE related to Herceptin therapy

• Any other malignancy in the last 5 years, except for basal cell cancer or cancer in situ of the cervix

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• pertuzumab [Perjeta]
Loading dose 840 mg intravenously on Day 2 of the first cycle. 420 mg every 3 weeks thereafter, until disease progression or unacceptable toxicity.
• Trastuzumab
Intravenous (IV) infusion of 2 milligrams per kilogram (mg/kg) 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Canada,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 With Pertuzumab and Trastuzumab	Objective 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 4.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8; then every 3 months until disease progression)	No
Primary	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 With Pertuzumab and Trastuzumab	Objective 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 4.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8; then every 3 months until disease progression)	No
Secondary	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	Objective 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 2.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8; then every 3 months until disease progression)	No
Secondary	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	Objective 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 2.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8; then every 3 months until disease progression)	No
Secondary	Duration of Response According to RECIST Version 1.0	Objective tumor response was assessed using RECIST version 1.0 to determine OR and CBR rates, as defined in previous outcome measures. The duration of OR was defined as the time from initial response of CR or PR to the time of disease progression or death. The duration of CBR was defined similarly as the time from initial response of CR or PR, or SD lasting at least 6 months, to the time of disease progression or death. 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 4.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8; then every 3 months until disease progression)	No
Secondary	Time to Response According to RECIST Version 1.0	Objective tumor response was assessed using RECIST version 1.0 to determine the OR rate, as defined in previous outcome measures. Time to response was defined as the time from first dose to the time of initial response of CR or PR. 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 4.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8; then every 3 months until disease progression)	No
Secondary	Percentage of Participants With Disease Progression According to RECIST Version 1.0	Objective 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 4.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8; then every 3 months until disease progression)	No
Secondary	Time to Progression (TTP) According to RECIST Version 1.0	Objective tumor response was assessed using RECIST version 1.0 to assess for disease progression, as defined in previous outcome measures. 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 4.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8; then every 3 months until disease progression)	No
Secondary	Progression-Free Survival (PFS) According to RECIST Version 1.0	Objective tumor response was assessed using RECIST version 1.0 to assess for disease progression, as defined in previous outcome measures. 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 4.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8; then every 3 months until disease progression)	No
Secondary	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)	No
Secondary	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)	No