A Study of Herceptin (Trastuzumab) in Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Advanced and/or Metastatic Breast Cancer

An Open-Label, Randomized Phase II Study of Herceptin (Trastuzumab), Taxotere (Docetaxel), and Xeloda (Capecitabine) in Combination, Versus Herceptin (Trastuzumab) Plus Taxotere (Docetaxel), in Patients With Advanced and/or Metastatic Breast Cancers That Overexpress HER2

This study will assess the efficacy and safety of intravenous (IV) trastuzumab (Herceptin) and IV docetaxel (Taxotere), with or without oral capecitabine (Xeloda), in women with previously untreated HER2-positive advanced and/or metastatic breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Taxotere; Drug: Herceptin; Drug: Xeloda

• Study Type: Interventional
• Enrollment (Actual): 225
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5011
  • Brisbane, Australia, 4066
  • Camperdown, Australia, 2050
  • Geelong, Australia, 3220
  • Melbourne, Australia, 3002
  • Melbourne, Australia, 3181
  • Perth, Australia, 6000
  • Southport, Australia, 4215
• Brazil
  • Porto Alegre, Brazil, 91350-200
  • Rio de Janeiro, Brazil, 20560-120
  • Sao Paulo, Brazil, 01401-901
• Canada
  • Quebec, Canada, G1S 4L8
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
• Costa Rica
  • San Jose, Costa Rica, 10103
• Finland
  • Turku, Finland, 20520
• France
  • Besancon, France, 25030
  • Grenoble, France, 38000
  • Marseille, France, 13273
  • Paris, France, 75231
  • Pierre Benite, France, 69310
  • Rennes, France, 35042
• Greece
  • Athens, Greece, 11526
  • Heraklion, Greece, 71110
  • Patras, Greece, 26500
• Guatemala
  • Guatemala City, Guatemala, 01010
• Italy
  • Legnago, Italy, 37045
  • Noale, Italy, 30033
  • Rozzano, Italy, 20089
  • Trento, Italy, 38100
  • Treviglio, Italy, 24047
• Mexico
  • Distrito Federal, Mexico, 14080
  • Merida, Mexico, 97500
  • Monterrey, Mexico, 64060
  • Monterrey, Mexico, 64020
• Panama
  • Panama City, Panama
• Poland
  • Gdansk, Poland, 80-214
  • Szczecin, Poland, 71-730
• Spain
  • Barcelona, Spain, 08035
  • Lerida, Spain, 25198
  • Sabadell, Barcelona, Spain, 08208
  • Zaragoza, Spain, 50009
• Sweden
  • Karlstad, Sweden, 65185
  • Västerås, Sweden, 72189
• United Kingdom
  • Ipswich, United Kingdom, IP4 5PD
  • Leeds, United Kingdom, LS9 7TF
  • Manchester, United Kingdom, M20 4BX
  • Northwood, United Kingdom, HA6 2RN
  • Oxford, United Kingdom, OX3 7LJ
  • Southampton, United Kingdom, SO16 6YD
  • Weston Super Mare, United Kingdom, BS23 4TQ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed, HER2-positive advanced and/or metastatic breast cancer not amenable to curative therapy
• At least one measurable lesion according to RECIST
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Baseline left ventricular ejection fraction (LVEF) at least 50%

Exclusion Criteria:

• Pregnant, lactating, or women of childbearing potential who are not surgically sterile or not willing to use adequate contraceptive methods
• Previous treatment with Herceptin or other anti-HER therapies, or any previous chemotherapy for advanced or metastatic disease
• Past medical history significant for any cardiac or central nervous system (CNS) disorders
• Poor hematologic, renal, or hepatic function
• Chronic corticosteroid therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Herceptin + Taxotere; Participants will receive dual therapy with Herceptin and Taxotere until disease progression, unmanageable toxicity, or withdrawal.	Drug: Taxotere; Participants will receive Taxotere, 75 milligrams per meter-squared (mg/m^2) in the Herceptin + Taxotere + Xeloda arm or 100 mg/m^2 in the Herceptin + Taxotere arm, via IV infusion on Day 1 of each 21-day cycle. The lower starting dose will be used in the triple-therapy arm.; Other Names: docetaxel; Drug: Herceptin; Participants will receive Herceptin, 6 milligrams per kilogram (mg/kg) via IV infusion, on Day 1 of each 21-day cycle. The first dose will be a loading dose of 8 mg/kg in Cycle 1; the dose of 6 mg/kg will be given from Cycle 2 onward.; Other Names: trastuzumab
EXPERIMENTAL: Herceptin + Taxotere + Xeloda; Participants will receive triple therapy with Herceptin, Taxotere, and Xeloda until disease progression, unmanageable toxicity, or withdrawal.	Drug: Taxotere; Participants will receive Taxotere, 75 milligrams per meter-squared (mg/m^2) in the Herceptin + Taxotere + Xeloda arm or 100 mg/m^2 in the Herceptin + Taxotere arm, via IV infusion on Day 1 of each 21-day cycle. The lower starting dose will be used in the triple-therapy arm.; Other Names: docetaxel; Drug: Herceptin; Participants will receive Herceptin, 6 milligrams per kilogram (mg/kg) via IV infusion, on Day 1 of each 21-day cycle. The first dose will be a loading dose of 8 mg/kg in Cycle 1; the dose of 6 mg/kg will be given from Cycle 2 onward.; Other Names: trastuzumab; Drug: Xeloda; Participants will receive oral Xeloda, 950 mg/m^2 twice a day on Days 1 to 14 of each 21-day cycle.; Other Names: capecitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST)	Tumor response was assessed by RECIST during the study. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a best overall response for CR or PR was reported. The exact 95% confidence interval (CI) for one-sample binomial was determined using the Pearson-Clopper method.	Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Death or Disease Progression According to RECIST	Tumor response was assessed by RECIST during the study. Disease progression or progressive disease (PD) was defined as ≥20% increase in sum LD in reference to the smallest on-treatment sum LD, or the appearance of new lesions. The percentage of participants who died or experienced PD was reported.	Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall)
Progression-Free Survival (PFS) According to RECIST	Tumor response was assessed by RECIST during the study. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-treatment sum LD, or the appearance of new lesions. PFS was defined as the time from start of treatment to the first event of death or PD. Participants without event at the time of analysis were censored at the latest date of last tumor assessment or last date in drug log. The median duration of PFS and corresponding 95% CI were estimated by Kaplan-Meier analysis and expressed in months.	Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall)
Percentage of Participants Who Died	The percentage of participants who died from any cause was reported.	Continuously during treatment (up to 66 months) and at any time after treatment discontinuation until 18 months after last participant enrolled (up to 66 months overall)
Overall Survival (OS)	OS was defined as the time from start of treatment to date of death for any reason. Participants who were alive at the time of analysis were censored at the latest date of last tumor assessment, last drug intake, or last follow-up information. The median duration of OS and corresponding 95% CI were estimated by Kaplan-Meier analysis and expressed in months.	Continuously during treatment (up to 66 months) and at any time after treatment discontinuation until 18 months after last participant enrolled (up to 66 months overall)
Duration of Response (DOR) According to RECIST	Tumor response was assessed by RECIST during the study. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. PR was defined as ≥30% decrease in sum LD of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. DOR was defined as the time from first assessment of CR or PR until the first occurrence of documented PD, death, or withdrawal. The median DOR was reported and expressed in months.	Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Hoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev. 2021 May 26;5(5):CD011220. doi: 10.1002/14651858.CD011220.pub2.

Study record dates

Study Major Dates

• Study Start: February 1, 2002
• Primary Completion (ACTUAL): March 1, 2006
• Study Completion (ACTUAL): January 1, 2008

Study Registration Dates

• First Submitted: April 20, 2016
• First Submitted That Met QC Criteria: April 20, 2016
• First Posted (ESTIMATE): April 22, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): November 22, 2016
• Last Update Submitted That Met QC Criteria: September 30, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Trastuzumab; Capecitabine
• Other Study ID Numbers: MO16419