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

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02015676
• Collaborator: (none)
• Enrollment: 69
• Location: 1
• Arms: 2
• Duration (Months): 98
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: trastuzumab; Drug: paclitaxel; Drug: Myocet	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 69 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: '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.'
• Study Start Date: Jul 1, 2001
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Madrid		Spain	28027

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Chair: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02015676
• Other Study ID Numbers: M77035
• First Posted: Dec 19, 2013
• Last Update Posted: Mar 12, 2015
• Last Verified: Feb 1, 2015

• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Trastuzumab

Study Results

Participant Flow

Arm/Group Title	Trastuzumab, Doxorubicin, Paclitaxel; Phase I	Trastuzumab, Doxorubicin, Paclitaxel; Phase II	Trastuzumab Doxorubicin, Paclitaxel; Phase I and Phase II
Arm/Group Description	Participants received an initial loading dose of trastuzumab 4 milligrams per kilogram (mg/kg), intravenously (IV), over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 40 mg per square meter (mg/m^2), IV, once 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; and paclitaxel 60 mg/m^2, IV, once per week, starting at 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.	Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.	During Phase I, participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 40 mg/m^2, IV, once every 3 weeks, for 2 treatment cycles, then the dose was increased to 50 mg/m^2, IV, and continued for 6 cycles; and paclitaxel 60 mg/m^2, IV, once per week, starting at Week 19 for 2 treatment cycles, then the dose was increased to 70 mg/m^2, IV, and subsequently 80 mg/m^2, IV, and continued until disease progression. In Phase II, participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.
Period Title: Overall Study
STARTED	15	48	6
COMPLETED	6	14	3
NOT COMPLETED	9	34	3

Baseline Characteristics

Arm/Group Title	Trastuzumab, Doxorubicin, Paclitaxel; Phase I	Trastuzumab, Doxorubicin, Paclitaxel; Phase II	Trastuzumab, Doxorubicin, Paclitaxel; Phase II and II	Total
Arm/Group Description	Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 40 mg/m^2, IV, once every 3 weeks, from Week 1. If no DLT was observed in ≥2/3 of cohort for 2 treatment cycles, the dose was increased to 50 mg/m^2, IV, and continued for 6 cycles; and paclitaxel 60 mg/m^2, IV, once per week, starting at 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.	Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.	During Phase I, participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 40 mg/m^2, IV, once every 3 weeks, for 2 treatment cycles, then the dose was increased to 50 mg/m^2, IV, and continued for 6 cycles; and paclitaxel 60 mg/m^2, IV, once per week, starting at Week 19 for 2 treatment cycles, then the dose was increased to 70 mg/m^2, IV, and subsequently 80 mg/m^2, IV, and continued until disease progression. In Phase II, participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.	Total of all reporting groups
Overall Participants	15	48	6	69
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.73 (12.42)	52.98 (12.33)	44.33 (15.36)	52.61 (12.70)
Sex: Female, Male (Count of Participants)
Female	15 100%	48 100%	6 100%	69 100%
Male	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) According to World Health Organization (WHO) Handbook for Reporting Results of Cancer Treatment
Description	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.
Time Frame	Baseline (BL), Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)

Outcome Measure Data

Analysis Population Description

All participants enrolled in Phase II of this study were included in the analysis.

Arm/Group Title	Trastuzumab, Doxorubicin, Paclitaxel; Phase II
Arm/Group Description	Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.
Measure Participants	54
CR	51.85 345.7%
PR	46.30 308.7%

2. Secondary Outcome

Title	Time to Disease Progression - Percentage of Participants With an Event
Description	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.
Time Frame	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)

Outcome Measure Data

Analysis Population Description

All participants enrolled in Phase II of this study were included in the analysis.

Arm/Group Title	Trastuzumab, Doxorubicin, Paclitaxel; Phase II
Arm/Group Description	Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.
Measure Participants	54
Number [percentage of participants]	40.74 271.6%

3. Secondary Outcome

Title	Time to Disease Progression
Description	The median time, in months, from the start of treatment to disease progression event.
Time Frame	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)

Outcome Measure Data

Analysis Population Description

All participants enrolled in Phase II of this study were included in the analysis.

Arm/Group Title	Trastuzumab, Doxorubicin, Paclitaxel; Phase II
Arm/Group Description	Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.
Measure Participants	54
Median (95% Confidence Interval) [months]	43.3018

4. Secondary Outcome

Title	Time to Treatment Response - Percentage of Participants With an Event
Description	Treatment response was defined as the time from the start of treatment to the date of recorded CR or PR of measurable disease.
Time Frame	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)

Outcome Measure Data

Analysis Population Description

All participants enrolled in Phase II of this study were included in the analysis.

Arm/Group Title	Trastuzumab, Doxorubicin, Paclitaxel; Phase II
Arm/Group Description	Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.
Measure Participants	54
Number [percentage participants]	98.15 654.3%

5. Secondary Outcome

Title	Time to Treatment Response
Description	The median time, in months, from the start of treatment to treatment response event.
Time Frame	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)

Outcome Measure Data

Analysis Population Description

All participants enrolled in Phase II of this study were included in the analysis.

Arm/Group Title	Trastuzumab, Doxorubicin, Paclitaxel; Phase II
Arm/Group Description	Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.
Measure Participants	54
Median (95% Confidence Interval) [months]	1.87269

6. Secondary Outcome

Title	Duration of Response - Percentage of Participants With an Event
Description	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 Frame	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)

Outcome Measure Data

Analysis Population Description

Only participants with a response were included in the analysis.

Arm/Group Title	Trastuzumab, Doxorubicin, Paclitaxel; Phase II
Arm/Group Description	Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.
Measure Participants	53
Number [percentage of participants]	39.62 264.1%

7. Secondary Outcome

Title	Duration of Response
Description	The median time, in months, from enrollment to duration of response event to Week 52.
Time Frame	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)

Outcome Measure Data

Analysis Population Description

All participants enrolled in Phase II of this study were included in the analysis.

Arm/Group Title	Trastuzumab, Doxorubicin, Paclitaxel; Phase II
Arm/Group Description	Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.
Measure Participants	54
Median (95% Confidence Interval) [months]	41.1006

8. Secondary Outcome

Title	Time to Therapy Failure - Percentage of Participants With an Event
Description	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 Frame	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)

Outcome Measure Data

Analysis Population Description

All participants enrolled in Phase II of this study were included in the analysis.

Arm/Group Title	Trastuzumab, Doxorubicin, Paclitaxel; Phase II
Arm/Group Description	Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.
Measure Participants	54
Number [percentage of participants]	81.48 543.2%

9. Secondary Outcome

Title	Time to Therapy Failure
Description	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.
Time Frame	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)

Outcome Measure Data

Analysis Population Description

All participants enrolled in Phase II of this study were included in the analysis.

Arm/Group Title	Trastuzumab, Doxorubicin, Paclitaxel; Phase II
Arm/Group Description	Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.
Measure Participants	54
Median (95% Confidence Interval) [months]	24.0821

10. Secondary Outcome

Title	Overall Survival (OS) - Percentage of Participants With an Event
Description	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.
Time Frame	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)

Outcome Measure Data

Analysis Population Description

All participants enrolled in Phase II of this study were included in the analysis.

Arm/Group Title	Trastuzumab, Doxorubicin, Paclitaxel; Phase II
Arm/Group Description	Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.
Measure Participants	54
Number [percentage of participants]	3.70 24.7%

11. Secondary Outcome

Title	Overall Survival
Description	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.
Time Frame	BL, Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)

Outcome Measure Data

Analysis Population Description

All participants enrolled in Phase II of this study were included in the analysis.

Arm/Group Title	Trastuzumab, Doxorubicin, Paclitaxel; Phase II
Arm/Group Description	Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.
Measure Participants	54
Mean (Standard Error) [months]	7.6909 (0.1338)

Adverse Events

Time Frame	BL, and Weeks 7, 13, 19, every 8 weeks thereafter until end of study.
Adverse Event Reporting Description	All participants who received at least 1 dose of study treatment and at least 1 safety follow-up were included in the safety analysis.
Arm/Group Title	Trastuzumab, Doxorubicin, Paclitaxel; Phase I & II
Arm/Group Description	Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours on Day 1 (Week 1), followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression; doxorubicin, 50 mg/m^2, IV, once every 3 weeks, starting at Week 1 for 6 cycles; and paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.
All Cause Mortality
	Trastuzumab, Doxorubicin, Paclitaxel; Phase I & II
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Trastuzumab, Doxorubicin, Paclitaxel; Phase I & II
	Affected / at Risk (%)	# Events
Total	26/69 (37.7%)
Blood and lymphatic system disorders
Thrombophlebitis	1/69 (1.4%)
Anaemia NOS	1/69 (1.4%)
Acute febrile neutrophilic dermatosis	1/69 (1.4%)
Cardiac disorders
Cardiac failure NOS	2/69 (2.9%)
Ejection fraction decreased	1/69 (1.4%)
Gastrointestinal disorders
Intestinal obstruction NOS	1/69 (1.4%)
Diarrhoea NOS	2/69 (2.9%)
General disorders
Febrile neutropenia	12/69 (17.4%)
Mucosal inflammation NOS	1/69 (1.4%)
Infections and infestations
Endocarditis	1/69 (1.4%)
Pancreatitis NOS	1/69 (1.4%)
Pancreatitis	1/69 (1.4%)
Respiratory tract infection NOS	1/69 (1.4%)
Upper respiratory tract infection NOS	1/69 (1.4%)
Staphylococcal infection	1/69 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system	1/69 (1.4%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	1/69 (1.4%)
Cough	2/69 (2.9%)
Dyspnoea	2/69 (2.9%)
Pneumonia NOS	2/69 (2.9%)
Skin and subcutaneous tissue disorders
Skin infection	1/69 (1.4%)
Other (Not Including Serious) Adverse Events
	Trastuzumab, Doxorubicin, Paclitaxel; Phase I & II
	Affected / at Risk (%)	# Events
Total	63/69 (91.3%)
Blood and lymphatic system disorders
Anaemia NOS	7/69 (10.1%)
Leukopenia NOS	3/69 (4.3%)
Lymphopenia	1/69 (1.4%)
Neutropenia	21/69 (30.4%)
Paratracheal lymphadenopathy	1/69 (1.4%)
Thrombocytopenia	1/69 (1.4%)
Cardiac disorders
Cardiotoxicty	2/69 (2.9%)
Ejection fraction decreased	11/69 (15.9%)
Palpitations	1/69 (1.4%)
Sinus tachycardia	2/69 (2.9%)
Tachycardia NOS	1/69 (1.4%)
Transient ischaemic attack	1/69 (1.4%)
Ventricular extrasystoles	1/69 (1.4%)
Ear and labyrinth disorders
Ear pain	1/69 (1.4%)
Eye disorders
Conjunctivitis	11/69 (15.9%)
Lacrimation increased	2/69 (2.9%)
Mydriasis	1/69 (1.4%)
Pupils unequal	1/69 (1.4%)
Vision blurred	1/69 (1.4%)
Gastrointestinal disorders
Abdominal pain NOS	5/69 (7.2%)
Abdominal pain upper	11/69 (15.9%)
Anal fissure	2/69 (2.9%)
Bowel sounds abnormal	1/69 (1.4%)
Cheilitis	1/69 (1.4%)
Constipation	10/69 (14.5%)
Diarrhoea NOS	29/69 (42%)
Dry mouth	1/69 (1.4%)
Dysgeusia	5/69 (7.2%)
Dyspepsia	12/69 (17.4%)
Dysphagia	2/69 (2.9%)
Gastroenteritis NOS	2/69 (2.9%)
Gingival pain	1/69 (1.4%)
Haematochezia	1/69 (1.4%)
Haemorrhoids	6/69 (8.7%)
Nausea	36/69 (52.2%)
Oesophagitis NOS	2/69 (2.9%)
Proctalgia	1/69 (1.4%)
Rectal tenesmus	1/69 (1.4%)
Stomatitis	10/69 (14.5%)
Toothache	1/69 (1.4%)
Vomiting NOS	26/69 (37.7%)
General disorders
Asthenia	35/69 (50.7%)
Catarrh	5/69 (7.2%)
Chest pain	3/69 (4.3%)
Chest wall pain	2/69 (2.9%)
Death NOS	1/69 (1.4%)
Face oedema	1/69 (1.4%)
Fatigue	17/69 (24.6%)
Hypophonesis	1/69 (1.4%)
Influenza like illness	4/69 (5.8%)
Intermittent pyrexia	1/69 (1.4%)
Nail discolouration	1/69 (1.4%)
Nail discomfort	1/69 (1.4%)
Nail disorder NOS	23/69 (33.3%)
Nail toxicity	5/69 (7.2%)
Not coded	1/69 (1.4%)
Odynophagia	3/69 (4.3%)
Oedema NOS	4/69 (5.8%)
Oedema peripheral	19/69 (27.5%)
Pain NOS	1/69 (1.4%)
Performance status decreased	1/69 (1.4%)
Pyrexia	23/69 (33.3%)
Rigors	7/69 (10.1%)
Scar pain	1/69 (1.4%)
Sweating increased	1/69 (1.4%)
Hepatobiliary disorders
Biliary colic	1/69 (1.4%)
Immune system disorders
Drug hypersensitivity	1/69 (1.4%)
Hypersensitivity NOS	1/69 (1.4%)
Milk allergy	1/69 (1.4%)
Skin reaction	1/69 (1.4%)
Infections and infestations
Catheter related infection	1/69 (1.4%)
Cellulitis	1/69 (1.4%)
Febrile neutropenia	2/69 (2.9%)
Furuncle	1/69 (1.4%)
Herpes simplex	3/69 (4.3%)
Herpes zoster	2/69 (2.9%)
Hordeolum	2/69 (2.9%)
Influenza viral infections	1/69 (1.4%)
Laryngitis NOS	1/69 (1.4%)
Lymphangitis	2/69 (2.9%)
Nail infection	1/69 (1.4%)
Nasopharyngitis	3/69 (4.3%)
Oral infection	2/69 (2.9%)
Otitis media NOS	1/69 (1.4%)
Pharyngitis	3/69 (4.3%)
Sinusitis NOS	1/69 (1.4%)
Skin infection	1/69 (1.4%)
Tinea pedis	1/69 (1.4%)
Upper respiratory tract infection NOS	4/69 (5.8%)
Urinary tract infection NOS	4/69 (5.8%)
Varicella	1/69 (1.4%)
Injury, poisoning and procedural complications
Humerus fracture	1/69 (1.4%)
Joint sprain	1/69 (1.4%)
Post procedural diarrhoea	1/69 (1.4%)
Post procedural vomiting	1/69 (1.4%)
Investigations
Blood bilirubin increased	1/69 (1.4%)
Haemoglobin abnormal	6/69 (8.7%)
Transaminases increased	1/69 (1.4%)
Weight increased	5/69 (7.2%)
Metabolism and nutrition disorders
Anorexia	10/69 (14.5%)
Hypercalcaemia	1/69 (1.4%)
Hypokalaemia	1/69 (1.4%)
Intertrigo candida	1/69 (1.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	11/69 (15.9%)
Back pain	15/69 (21.7%)
Bone pain	6/69 (8.7%)
Limb discomfort NOS	1/69 (1.4%)
Muscle weakness NOS	1/69 (1.4%)
Musculoskeletal discomfort	1/69 (1.4%)
Myalgia	9/69 (13%)
Neck pain	2/69 (2.9%)
Osteoarthritis	1/69 (1.4%)
Pain in extremity	2/69 (2.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast abscess	1/69 (1.4%)
Breast haemorrhage	1/69 (1.4%)
Lymphoma	1/69 (1.4%)
Mycosis fungoides	1/69 (1.4%)
Nervous system disorders
Aphonia	1/69 (1.4%)
Dizziness	5/69 (7.2%)
Dysaesthesia	3/69 (4.3%)
Extrapyramidal disorder	1/69 (1.4%)
Headache	9/69 (13%)
Neuropathic pain	1/69 (1.4%)
Neuropathy NOS	5/69 (7.2%)
Neurotoxicity NOS	1/69 (1.4%)
Paraesthesia	18/69 (26.1%)
Paralysis	1/69 (1.4%)
Peripheral neuropathy NOS	1/69 (1.4%)
Peripheral sensory neuropathy	6/69 (8.7%)
Syncope	2/69 (2.9%)
Psychiatric disorders
Anxiety symptoms	2/69 (2.9%)
Depression	8/69 (11.6%)
Insomnia	7/69 (10.1%)
Nervousness	1/69 (1.4%)
Renal and urinary disorders
Cystitis-like symptom	1/69 (1.4%)
Dysuria	2/69 (2.9%)
Pollakiuria	1/69 (1.4%)
Reproductive system and breast disorders
Amenorrhoea NOS	9/69 (13%)
Breast pain	2/69 (2.9%)
Menometrorrhagia	1/69 (1.4%)
Respiratory, thoracic and mediastinal disorders
Bronchitis NOS	2/69 (2.9%)
Bronchospasm NOS	1/69 (1.4%)
Congestion	1/69 (1.4%)
Cough	9/69 (13%)
Dyspnoea	11/69 (15.9%)
Epistaxis	13/69 (18.8%)
Hiccups	1/69 (1.4%)
Injury asphyxiation	1/69 (1.4%)
Mucosal inflammation NOS	40/69 (58%)
Nasal dryness	2/69 (2.9%)
Oropharyngeal candidiasis	1/69 (1.4%)
Pulmonary embolism	1/69 (1.4%)
Respiratory failure	1/69 (1.4%)
Rhinorrhoea	3/69 (4.3%)
Skin and subcutaneous tissue disorders
Alopecia	54/69 (78.3%)
Body tinea	1/69 (1.4%)
Dermatitis NOS	1/69 (1.4%)
Dermatitis radiation NOS	7/69 (10.1%)
Dry skin	2/69 (2.9%)
Erythema	13/69 (18.8%)
Folliculitis	1/69 (1.4%)
Hand dermatitis	1/69 (1.4%)
Onycholysis	9/69 (13%)
Palmar erythema	1/69 (1.4%)
Palmar-plantar erythrodysaesthesia syndrome	10/69 (14.5%)
Pigmentation disorder NOS	4/69 (5.8%)
Pruritus	7/69 (10.1%)
Rash NOS	10/69 (14.5%)
Skin hyperpigmentation	8/69 (11.6%)
Skin toxicity	5/69 (7.2%)
Vascular disorders
Flushing	4/69 (5.8%)
Hypotension NOS	1/69 (1.4%)
Lymphoedema NOS	9/69 (13%)
Phlebitis NOS	2/69 (2.9%)
Varicophlebitis	1/69 (1.4%)
Varicose veins NOS	1/69 (1.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.