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

NCT01998906 | Completed Phase 3 Results

• 1 other identifier: MO16432
• Study Type: interventional
• Target: 330
• Locations: 6 countries
• Sites: 36

Brief 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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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

Secondary Outcomes (8)

• Percentage of Participants With Breast Pathological Complete Response (bpCR)

  BL, Day 1 of Cycles 1-10 (pre-surgery)

• Percentage of Participants With Total Pathological Complete Response (tpCR)

  BL, Day 1 of Cycles 1-10 (pre-surgery)

• Percentage of Participants Achieving Either Complete Response (CR) or Partial Response (PR) According to Modified Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

  BL, Presurgery: Day 1 of Cycles 1-10

• Overall Survival (OS) - Percentage of Participants With an 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

• Overall Survival

  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

Study Arms (3)

HER-2+ Trastuzumab, Doxorubicin/Paclitaxel/CMF

EXPERIMENTAL

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; Drug: Doxorubicin; Drug: Paclitaxel; Drug: CMF

HER-2+ Doxorubicin/Paclitaxel/CMF

ACTIVE COMPARATOR

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; Drug: Paclitaxel; Drug: CMF

HER-2- Doxorubicin/Paclitaxel/CMF

ACTIVE COMPARATOR

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; Drug: Paclitaxel; Drug: CMF

Interventions

Trastuzumab DRUG

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

Also known as: Herceptin

HER-2+ Trastuzumab, Doxorubicin/Paclitaxel/CMF

Doxorubicin DRUG

60 mg/m2 IV on Day 1 of Cycles 1 through 3

HER-2+ Doxorubicin/Paclitaxel/CMF; HER-2+ Trastuzumab, Doxorubicin/Paclitaxel/CMF; HER-2- Doxorubicin/Paclitaxel/CMF

Paclitaxel DRUG

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

HER-2+ Doxorubicin/Paclitaxel/CMF; HER-2+ Trastuzumab, Doxorubicin/Paclitaxel/CMF; HER-2- Doxorubicin/Paclitaxel/CMF

CMF DRUG

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

HER-2+ Doxorubicin/Paclitaxel/CMF; HER-2+ Trastuzumab, Doxorubicin/Paclitaxel/CMF; HER-2- Doxorubicin/Paclitaxel/CMF

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• previous therapy for any invasive malignancy.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (36)

Unknown Facility

Vienna, 1090, Austria

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München, 80637, Germany

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San Giovanni Rotondo, Apulia, 71013, Italy

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Bologna, Emilia-Romagna, 40138, Italy

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Carpi, Emilia-Romagna, 41012, Italy

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Udine, Friuli Venezia Giulia, 33100, Italy

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Milan, Lombardy, 20133, Italy

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Pavia, Lombardy, 27100, Italy

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Varese, Lombardy, 21100, Italy

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Sassari, Sardinia, 07100, Italy

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Trento, Trentino-Alto Adige, 38100, Italy

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Pisa, Tuscany, 56100, Italy

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Bellunoi, Veneto, 32100, Italy

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Castelfranco Veneto, Veneto, 31033, Italy

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Mirano, Veneto, 30035, Italy

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Santorso, Veneto, 36014, Italy

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Vicenza, Veneto, 36100, Italy

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Lisbon, 1099-023, Portugal

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Kazan', 420029, Russia

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Moscow, 107005, Russia

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Moscow, 115478, Russia

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Moscow, 117837, Russia

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Moscow, 129128, Russia

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Saint Petersburg, 197022, Russia

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Saint Petersburg, 197758, Russia

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Barcelona, Barcelona, 08022, Spain

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Barcelona, Barcelona, 08035, Spain

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Barcelona, Barcelona, 08041, Spain

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Barcelona, Barcelona, 08907, Spain

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Terrassa, Barcelona, 08221, Spain

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Jerez de la Frontera, Cadiz, 11407, Spain

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Donostia / San Sebastian, Guipuzcoa, 20080, Spain

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Madrid, Madrid, 28041, Spain

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Valencia, Valencia, 46009, Spain

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Valencia, Valencia, 46010, Spain

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Zaragoza, Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Doxorubicin; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffman-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2013
• First Posted: December 2, 2013
• Study Start: May 1, 2002
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: October 28, 2014
• Results First Posted: October 28, 2014

Record last verified: 2014-10

Locations

DE (1); AU (1); PT (1); RU (7); ES (11); IT (15)