A Study of Herceptin (Trastuzumab) in Combination Chemotherapy in Patients With Metastatic or Locally Advanced Breast Cancer
- Registration Number
- NCT02015676
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 69
- women 18-70 years of age;
- metastatic or locally advanced breast cancer;
- HER2 overexpression;
- >= 1 measurable lesion.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Trastuzumab, Myocet, Paclitaxel; Phase II trastuzumab 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. Trastuzumab, Myocet, Paclitaxel; Phase I trastuzumab 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. Trastuzumab, Myocet, Paclitaxel; Phase I paclitaxel 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. Trastuzumab, Myocet, Paclitaxel; Phase I Myocet 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. Trastuzumab, Myocet, Paclitaxel; Phase II paclitaxel 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. Trastuzumab, Myocet, Paclitaxel; Phase II Myocet 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) According to World Health Organization (WHO) Handbook for Reporting Results of Cancer Treatment Baseline (BL), Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years) 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.
- Secondary Outcome Measures
Name Time Method Time to Treatment Response BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years) The median time, in months, from the start of treatment to treatment response event.
Duration of Response BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years) The median time, in months, from enrollment to duration of response event to Week 52.
Time to Treatment Response - Percentage of Participants With an Event BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years) Treatment response was defined as the time from the start of treatment to the date of recorded CR or PR of measurable disease.
Time to Disease Progression BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years) The median time, in months, from the start of treatment to disease progression event.
Time to Disease Progression - Percentage of Participants With an Event BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years) 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.
Overall Survival BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years) 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.
Duration of Response - Percentage of Participants With an Event BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years) 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.
Time to Therapy Failure - Percentage of Participants With an Event BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years) 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.
Time to Therapy Failure BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years) 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.
Overall Survival (OS) - Percentage of Participants With an Event BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years) 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.