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.'

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02015676

Enrollment

Registered

2013-12-19

Start date

2001-07-31

Completion date

2009-09-30

Last updated

2015-03-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

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.

Interventions

DRUGpaclitaxel

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

DRUGtrastuzumab

Initial loading does of 4 mg/kg IV, followed by 2 mg/kg IV weekly, until disease progression

DRUGMyocet

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

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 70 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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 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 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 - 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 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.
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.
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	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.

Countries

Spain

Participant flow

Participants by arm

Arm	Count
Trastuzumab, Doxorubicin, Paclitaxel; 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, 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.	15
Trastuzumab, Doxorubicin, Paclitaxel; 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.	48
Trastuzumab, Doxorubicin, Paclitaxel; Phase II and II 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.	6
Total	69

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Administrative reasons	0	3	1
Overall Study	Adverse Event	2	18	0
Overall Study	Death	0	1	0
Overall Study	Disease progression	3	1	1
Overall Study	Lack of Efficacy	2	4	0
Overall Study	Protocol Violation	1	0	0
Overall Study	Withdrawal by Subject	1	7	1

Baseline characteristics

Characteristic	Trastuzumab, Doxorubicin, Paclitaxel; Phase I	Trastuzumab, Doxorubicin, Paclitaxel; Phase II	Trastuzumab, Doxorubicin, Paclitaxel; Phase II and II	Total
Age, Continuous	54.73 years STANDARD_DEVIATION 12.42	52.98 years STANDARD_DEVIATION 12.33	44.33 years STANDARD_DEVIATION 15.36	52.61 years STANDARD_DEVIATION 12.7
Sex: Female, Male Female	15 Participants	48 Participants	6 Participants	69 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	63 / 69
serious Total, serious adverse events	26 / 69

Outcome results

Primary

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.

Time frame: Baseline (BL), Weeks 7, 13, 19, every 8 weeks thereafter until end of study (for up to 3 years)

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

Arm	Measure	Group	Value (NUMBER)
Trastuzumab, Doxorubicin, Paclitaxel; Phase II	Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) According to World Health Organization (WHO) Handbook for Reporting Results of Cancer Treatment	CR	51.85 percentage of participants
Trastuzumab, Doxorubicin, Paclitaxel; Phase II	Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) According to World Health Organization (WHO) Handbook for Reporting Results of Cancer Treatment	PR	46.30 percentage of participants

Secondary