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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01998906
First received: November 25, 2013
Last updated: October 24, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Trastuzumab
Drug: Doxorubicin
Drug: Paclitaxel
Drug: CMF
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Event-Free Survival (EFS) - Percentage of Participants With an Event [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Event-Free Survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The median time, in months, between randomization and date of documented occurrence of an EFS event.

  • Percentage of Participants Event Free at 1 Year [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Percentage of Participants Event Free at 2 Years [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Percentage of Participants Event Free at 3 Years [ Time Frame: 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Participants With Breast Pathological Complete Response (bpCR) [ Time Frame: BL, Day 1 of Cycles 1-10 (pre-surgery) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Total Pathological Complete Response (tpCR) [ Time Frame: BL, Day 1 of Cycles 1-10 (pre-surgery) ] [ Designated as safety issue: No ]
    tpCR was defined as a determination of bpCR and an absence of positive axillary nodes on pathology.

  • Percentage of Participants Achieving Either Complete Response (CR) or Partial Response (PR) According to Modified Response Evaluation Criteria in Solid Tumors (RECIST) Criteria [ Time Frame: BL, Presurgery: Day 1 of Cycles 1-10 ] [ Designated as safety issue: No ]
    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.

  • Overall Survival (OS) - Percentage of Participants With an Event [ Time Frame: 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 ] [ Designated as safety issue: No ]
    OS was defined as the time from the date of randomization to the date of the death due to any cause.

  • Overall Survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
    OS was defined as the time from the date of randomization to the date of the death due to any cause.

  • Percentage of Participants Surviving at 1 Year [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Percentage of Participants Surviving at 2 Years [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Percentage of Participants Surviving at 3 Years [ Time Frame: 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 ] [ Designated as safety issue: No ]

Enrollment: 330
Study Start Date: May 2002
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HER-2+ Trastuzumab, Doxorubicin/Paclitaxel/CMF
Participants with HER2 proto-oncogene positive breast cancer (HER2+) were treated with trastuzumab 8 milligrams per kilogram (mg/kg), intravenous (IV), on Day 1 of Cycle 1, followed by 6 mg/kg, IV, on Day 1 of Cycle 2 to up a maximum of Cycle 17. Participants also received doxorubicin 60 mg/ square meter (m^2), IV, and paclitaxel 150 mg/m^2, IV, on Day 1 of Cycles 1 through 3. Followed by paclitaxel 175 mg/m^2, IV, alone on Day 1 of Cycles 4 through 7. Participants also received CMF: cyclophosphamide 600 mg/m^2, IV; methotrexate 40 mg/m^2, IV; and 5-fluorouracil 600 mg/m^2, IV, on Day 1 of Cycles 8 through 10.
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
Other Name: Herceptin
Drug: Doxorubicin
60 mg/m2 IV on Day 1 of Cycles 1 through 3
Drug: 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
Drug: 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
Active Comparator: HER-2+ Doxorubicin/Paclitaxel/CMF
Participants with HER2 proto-oncogene positive breast cancer were treated with doxorubicin 60 mg/m^2, IV, and paclitaxel 150 mg/m^2, IV, on Day 1 of Cycles 1 through 3. Followed by paclitaxel 175 mg/m^2, IV, alone on Day 1 of Cycles 4 through 7. Participants also received CMF on Day 1 of Cycle 8 through 10.
Drug: Doxorubicin
60 mg/m2 IV on Day 1 of Cycles 1 through 3
Drug: 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
Drug: 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
Active Comparator: HER-2- Doxorubicin/Paclitaxel/CMF
Participants with HER2 proto-oncogene negative breast cancer were treated with doxorubicin 60 mg/m^2, IV, and paclitaxel 150 mg/m^2, IV, on Day 1 of Cycles 1 through 3. Followed by paclitaxel 175 mg/m^2, IV, alone on Day 1 of Cycles 4 through 7. Participants also received CMF on Day 1 of Cycle 8 through 10.
Drug: Doxorubicin
60 mg/m2 IV on Day 1 of Cycles 1 through 3
Drug: 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
Drug: 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • previous therapy for any invasive malignancy.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01998906

Locations
Austria
Wien, Austria, 1090
Germany
Muenchen, Germany, 80637
Italy
Bologna, Emilia-Romagna, Italy, 40138
Carpi, Emilia-Romagna, Italy, 41012
Udine, Friuli-Venezia Giulia, Italy, 33100
Milano, Lombardia, Italy, 20133
Pavia, Lombardia, Italy, 27100
Varese, Lombardia, Italy, 21100
San Giovanni Rotondo, Puglia, Italy, 71013
Sassari, Sardegna, Italy, 07100
Pisa, Toscana, Italy, 56100
Trento, Trentino-Alto Adige, Italy, 38100
Bellunoi, Veneto, Italy, 32100
Castelfranco Veneto, Veneto, Italy, 31033
Mirano, Veneto, Italy, 30035
Santorso, Veneto, Italy, 36014
Vicenza, Veneto, Italy, 36100
Portugal
Lisboa, Portugal, 1099-023
Russian Federation
Kazan, Russian Federation, 420029
Moscow, Russian Federation, 129128
Moscow, Russian Federation, 107005
Moscow, Russian Federation, 115478
Moscow, Russian Federation, 117837
Saint-Petersburg, Russian Federation, 197758
St Petersburg, Russian Federation, 197022
Spain
Terrassa, Barcelona, Spain, 08221
Jerez de La Frontera, Cadiz, Spain, 11407
San Sebastian, Guipuzcoa, Spain, 20080
Barcelona, Spain, 08907
Barcelona, Spain, 08035
Barcelona, Spain, 08022
Barcelona, Spain, 08041
Madrid, Spain, 28041
Valencia, Spain, 46009
Valencia, Spain, 46010
Zaragoza, Spain, 50009
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Chair: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01998906     History of Changes
Other Study ID Numbers: MO16432
Study First Received: November 25, 2013
Results First Received: July 18, 2014
Last Updated: October 24, 2014
Health Authority: Italy: Ministry of Health

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Doxorubicin
Liposomal doxorubicin
Paclitaxel
Trastuzumab
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Tubulin Modulators

ClinicalTrials.gov processed this record on April 27, 2015