A Study of Herceptin (Trastuzumab) in Combination Chemotherapy in Patients With Metastatic or Locally Advanced Breast Cancer

'A Study of the Effect of First Line Treatment With Paclitaxel and Myocet in Combination With Herceptin on Overall Tumor Response in Patients With Metastatic or Locally Advanced Breast Cancer and HER2 Overexpression.'

This study will define an optimal chemotherapy dose regimen of Myocet in combination with paclitaxel and intravenous Herceptin and will evaluate the efficacy and safety of this dose regimen in patients with metastatic or locally advanced breast cancer and HER2 overexpression. The anticipated time on study treatment is 3-12 months.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: trastuzumab; Drug: paclitaxel; Drug: Myocet

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28027

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• women 18-70 years of age;
• metastatic or locally advanced breast cancer;
• HER2 overexpression;
• >= 1 measurable lesion.

Exclusion Criteria:

• prior treatment for advanced breast cancer;
• prior treatment with Herceptin;
• bone or central nervous system metastasis as the only site of disease;
• history of another malignancy (except basal cell skin cancer and cancer in situ of the uterine cervix, and contralateral breast cancer) within 5 years of study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trastuzumab, Myocet, Paclitaxel; Phase I; Participants received an initial loading dose of trastuzumab 4 milligrams per kilogram (mg/kg), intravenously (IV), over 1.5 hours during Week 1, followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression. Participants also received myocet, 40 mg/ square meter (m^2), IV, every 3 weeks, from Week 1; if no dose limiting toxicity (DLT) was observed in greater than or equal to (≥) two-thirds (2/3) of cohort for 2 treatment cycles, the dose was increased to 50 mg/m^2, IV, and continued for 6 cycles. Participants also received paclitaxel 60 mg/ m^2, IV, once per week, from Week 19; if no DLT was observed in ≥ 2/3 of cohort for 2 treatment cycles, the dose was increased to 70 mg/m^2, IV, and subsequently 80 mg/m^2, IV, and continued until disease progression.	Drug: trastuzumab; Initial loading does of 4 mg/kg IV, followed by 2 mg/kg IV weekly, until disease progression; Other Names: Herceptin; Drug: paclitaxel; 60 mg/m^2 IV weekly; dose increased to 70 mg/m^2, and subsequently 80 mg/m^2, after 2 treatment cycles with no evidence of DLT until disease progression; Drug: Myocet; 40 mg/m^2 IV weekly; dose increased to 50 mg/m^2 IV after 2 treatment cycles with no evidence of DLT for 6 cycles
Experimental: Trastuzumab, Myocet, Paclitaxel; Phase II; Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours during Week 1, followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression. Participants also received myocet, 50 mg/m^2, IV, every 3 weeks, from Week 1 for 6 cycles. Participants also received paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.	Drug: trastuzumab; Initial loading does of 4 mg/kg IV, followed by 2 mg/kg IV weekly, until disease progression; Other Names: Herceptin; Drug: paclitaxel; 60 mg/m^2 IV weekly; dose increased to 70 mg/m^2, and subsequently 80 mg/m^2, after 2 treatment cycles with no evidence of DLT until disease progression; Drug: Myocet; 40 mg/m^2 IV weekly; dose increased to 50 mg/m^2 IV after 2 treatment cycles with no evidence of DLT for 6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) According to World Health Organization (WHO) Handbook for Reporting Results of Cancer Treatment	For measurable disease, CR was defined as the disappearance of all clinically detectable disease determined by 2 observations not less than 4 weeks apart; and PR was defined as a 50 percent (%) decrease in the sum of the products of the 2 greatest diameters of all measurable lesions by 2 observations not less than 4 weeks apart, and no appearance of new lesions or progression of any lesion. For immeasurable disease, CR was defined as the complete disappearance of all known disease for at least 4 weeks; and PR was defined as an estimated decrease in tumor size of 50% or more for at least 4 weeks.	Baseline (BL), Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Disease Progression - Percentage of Participants With an Event	Disease progression was defined as the time from the start of treatment to the date of the first recorded incident of disease progression, or the date of death due any cause. For measurable disease, disease progression was defined as a ≥25% increase in the sum of the products of diameters of 1 or more measurable lesions with a minimal area of greater than (>)2 square centimeters (cm^2), or the appearance of new lesions; and for malignant lesions with a minimal area of 2 cm^2, an increase of ≥1 cm^2. For immeasurable disease, disease progression was defined as the appearance of any new lesion not previously identified or an estimated increase of ≥50% in existent lesions.	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)
Time to Disease Progression	The median time, in months, from the start of treatment to disease progression event.	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)
Time to Treatment Response - Percentage of Participants With an Event	Treatment response was defined as the time from the start of treatment to the date of recorded CR or PR of measurable disease.	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)
Time to Treatment Response	The median time, in months, from the start of treatment to treatment response event.	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)
Duration of Response - Percentage of Participants With an Event	Duration of response was defined as the time from date CR was first recorded to the date progressive disease (PD) was first noted. For measurable disease, PD was defined as a ≥25% increase in the sum of the products of diameters of 1 or more measurable lesions with a minimal area of >2 cm^2, or the appearance of new lesions; and for malignant lesions with a minimal area of 2 cm^2, an increase of ≥1 cm^2. For immeasurable disease, PD was defined as the appearance of any new lesion not previously identified or an estimated increase of ≥50% in existent lesions.	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)
Duration of Response	The median time, in months, from enrollment to duration of response event to Week 52.	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)
Time to Therapy Failure - Percentage of Participants With an Event	Therapy failure was defined as the date of the start of therapy to the date of withdrawal due to adverse events, progressive disease/insufficient therapeutic response, death, failure to return, or refusal of treatment/lack of cooperation/withdrawal of consent. Participants were censored at the last dose of treatment if no event was recorded.	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)
Time to Therapy Failure	The median time, in months, from treatment start to therapy failure event. Participants were censored at the last date of treatment if no event was recorded.	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)
Overall Survival (OS) - Percentage of Participants With an Event	OS was defined as the time from the date of the start of treatment to the date of death or the last date the participant was known to be alive.	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)
Overall Survival	The time, in months, from the start of treatment to OS event. The mean survival time and it's standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: July 1, 2001
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: December 3, 2013
• First Submitted That Met QC Criteria: December 13, 2013
• First Posted (Estimate): December 19, 2013

Study Record Updates

• Last Update Posted (Estimate): March 12, 2015
• Last Update Submitted That Met QC Criteria: February 26, 2015
• Last Verified: February 1, 2015

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; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Paclitaxel; Trastuzumab
• Other Study ID Numbers: M77035