A Study of Herceptin (Trastuzumab) in Combination Chemotherapy in Women With Locally Advanced Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Randomized, Open-label Study of the Effect of Paclitaxel, Doxorubicin, and CMF Neoadjuvant Chemotherapy, With and Without Herceptin, on Tumor Response in Women With HER2-positive Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01998906
• Other study ID #: MO16432
• Status: Completed
• Phase: Phase 3
• First received: November 25, 2013
• Last updated: October 24, 2014
• Start date: May 2002
• Est. completion date: July 2012

Study information

• Verified date: October 2014
• 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 assess the efficacy and safety of adding Herceptin to a paclitaxel-containing regimen followed by cyclophosphamide/methotrexate/fluorouracil (CMF) chemotherapy in women with locally advanced breast cancer and HER2/c-erbB-2 gene amplification. In a parallel observational study patients with HER2-negative disease will receive the same chemotherapy without Herceptin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 330
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• female patients, >=18 years of age, with locally advanced breast cancer.

Exclusion Criteria:

• previous therapy for any invasive malignancy.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Trastuzumab
8mg/kg IV on Day 1 of Cycle 1, followed by 6 mg/kg on Day 1 of Cycle 2 up a maximum of Cycle 17
• Doxorubicin
60 mg/m2 IV on Day 1 of Cycles 1 through 3
• Paclitaxel
150 mg/m2 IV on Day 1 of Cycles 1 through 3, followed by 175 mg/m2 IV on Day 1 of Cycles 4 through 7
• CMF
CMF: Cyclophosphamide (600 mg/m2 IV bolus), methotrexate (40 mg/m2 IV bolus), 5-fluorouracil (600 mg/m2 IV bolus) on Day 1 of Cycles 8 through 10

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Austria,  Germany,  Italy,  Portugal,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-Free Survival (EFS) - Percentage of Participants With an Event	EFS was defined as the time between randomization and date of documented occurrence of disease recurrence or progression (local, regional, distant or contralateral) or death due to any cause.	Baseline (BL), Presurgery: Day 1 (Cycles 1-7) and Days 1 and 8 (Cycles 8-10); Postsurgery: Day 1 (Cycles 1-17); every 6 months up to 60 months after last dose of study drug; yearly thereafter	No
Primary	Event-Free Survival	The median time, in months, between randomization and date of documented occurrence of an EFS event.	BL, Presurgery: Day 1 (Cycles 1-7) and Days 1 and 8 (Cycles 8-10); Postsurgery: Day 1 (Cycles 1-17); every 6 months up to 60 months after last dose of study drug; yearly thereafter	No
Primary	Percentage of Participants Event Free at 1 Year		BL, Presurgery: Day 1 (Cycles 1-7) and Days 1 and 8 (Cycles 8-10); Postsurgery: Day 1 (Cycles 1-17); every 6 months up to 60 months after last dose of study drug; yearly thereafter	No
Primary	Percentage of Participants Event Free at 2 Years		BL, Presurgery: Day 1 (Cycles 1-7) and Days 1 and 8 (Cycles 8-10); Postsurgery: Day 1 (Cycles 1-17); every 6 months up to 60 months after last dose of study drug; yearly thereafter	No
Primary	Percentage of Participants Event Free at 3 Years		BL, Presurgery: Day 1 (Cycles 1-7) and Days 1 and 8 (Cycles 8-10); Postsurgery: Day 1 (Cycles 1-17); every 6 months up to 60 months after last dose of study drug; yearly thereafter	No
Secondary	Percentage of Participants With Breast Pathological Complete Response (bpCR)	bpCR was defined as an absence of any invasive cancer cell of the primary tumor at the time of major surgery after neoadjuvant chemotherapy with and without trastuzumab.	BL, Day 1 of Cycles 1-10 (pre-surgery)	No
Secondary	Percentage of Participants With Total Pathological Complete Response (tpCR)	tpCR was defined as a determination of bpCR and an absence of positive axillary nodes on pathology.	BL, Day 1 of Cycles 1-10 (pre-surgery)	No
Secondary	Percentage of Participants Achieving Either Complete Response (CR) or Partial Response (PR) According to Modified Response Evaluation Criteria in Solid Tumors (RECIST) Criteria	Assessments were made based on objective tumor measurements of the lesions as recorded in the case report form. In inflammatory cancer, progressive disease (PD) was defined as progression of any of the 2 signs of breast edema and erythema. In non-inflammatory cancer, PD was concluded if either the investigator judged the participant as having progressed at any time prior to surgery, or there was at least a 20% increase in the sum of target lesions (TLs), any new lesion, or clear progression of any nontarget lesion (NTLs). Clear progression of any NTL was defined as at least a 20% increase in the sum of NTLs compared to BL. PR was defined as at least a 30% decrease from BL in the sum of the longest diameter of TLs. CR was defined as no PD as assessed by the investigator and complete disappearance of all lesions.	BL, Presurgery: Day 1 of Cycles 1-10	No
Secondary	Overall Survival (OS) - Percentage of Participants With an Event	OS was defined as the time from the date of randomization to the date of the death due to any cause.	BL, Presurgery: Day 1 (Cycles 1-7) and Days 1 and 8 (Cycles 8-10); Postsurgery: Day 1 (Cycles 1-17); every 6 months up to 60 months after last dose of study drug; yearly thereafter	No
Secondary	Overall Survival	OS was defined as the time from the date of randomization to the date of the death due to any cause.	BL, Presurgery: Day 1 (Cycles 1-7) and Days 1 and 8 (Cycles 8-10); Postsurgery: Day 1 (Cycles 1-17); every 6 months up to 60 months after last dose of study drug; yearly thereafter	No
Secondary	Percentage of Participants Surviving at 1 Year		BL, Presurgery: Day 1 (Cycles 1-7) and Days 1 and 8 (Cycles 8-10); Postsurgery: Day 1 (Cycles 1-17); every 6 months up to 60 months after last dose of study drug; yearly thereafter	No
Secondary	Percentage of Participants Surviving at 2 Years		BL, Presurgery: Day 1 (Cycles 1-7) and Days 1 and 8 (Cycles 8-10); Postsurgery: Day 1 (Cycles 1-17); every 6 months up to 60 months after last dose of study drug; yearly thereafter	No
Secondary	Percentage of Participants Surviving at 3 Years		BL, Presurgery: Day 1 (Cycles 1-7) and Days 1 and 8 (Cycles 8-10); Postsurgery: Day 1 (Cycles 1-17); every 6 months up to 60 months after last dose of study drug; yearly thereafter	No