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Efficacy and Safety of Adjuvant Docetaxel and Trastuzumab in Stage I HER2-positive Breast Cancer

Primary Purpose

HER2-positive Breast Cancer, Adjuvant Therapy

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Paclitaxel

Trastuzumab

Docetaxel

About this trial

This is an interventional treatment trial for HER2-positive Breast Cancer focused on measuring Docetaxel, Paclitaxel

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Female aged 18 - 70 years old;
The histopathological confirm of invasive breast cancer;
HER-2 positive: immuno-histochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) confirmed amplification of erbb2 gene;
Tumor must be ≤ 2cm in greatest dimension, negative axillary lymph node or with micrometastasis (axillary nodes with tumor clusters ≤ 0.2cm);
No more than 90 days from the patient's most recent breast surgery for this breast cancer;
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;
Adequate bone marrow function: neutrophil ≥ 1500/mm^3, hemoglobin ≥ 9 g/dl, and platelets ≥ 100,000/mm^3;
Adequate liver and renal function: creatinine ≤ 1.5 folds of the upper limit of normal value; aspartate aminotransferase and alanine aminotransferase ≤ 1.5 folds of the upper limit of normal value, aspartate aminotransferase and alanine aminotransferase ≤ 2 folds of the upper limit of normal value for patient with Gilbert 's syndrome;
Left ventricular ejection fraction (LVEF) ≥ 50%;
Willing and able to sign informed consent.

Exclusion Criteria:

Any of the following due to teratogenic potential of chemotherapy: pregnant women, nursing women, women of childbearing potential who are unwilling to employ adequate contraception;
Locally advanced tumors at diagnosis, including tumors fixed to the chest wall, peau d'orange, skin ulcerations/nodules, or clinical inflammatory changes;
History of prior chemotherapy in the past 5 years;
History of prior trastuzumab therapy;
Patients with a history of previous invasive breast cancer;
Active, unresolved infection;
Prior history of any other malignancy in the past 5 years, except for early stage tumors of the skin or cervix treated with curative intent;
Can not tolerate or be allergic to chemotherapy, anti-HER-2 therapy or pharmaceutical materials such as benzyl alcohol;
≥ grade 2 neuropathy;
Active cardiac disease: Any prior myocardial infarction (asymptomatic changes on EKG suggestive of old myocardial infarction is not an exclusion); Documented congestive heart failure (CHF); Current use of any therapy specifically for CHF; Current uncontrolled hypertension (diastolic >100 mmHg or systolic > 200 mmHg); Clinically significant pericardial effusion;
The antibody of hepatitis C virus, HIV or Treponema pallidum positive; HBsAg positive and hepatitis B virus DNA in peripheral blood ≥ 10^3 copy/mL；
Enrollment on other Investigational studies within 30 days;
Not allowed by the investigators.

Sites / Locations

2nd Affiliated Hospital, School of Medicine, Zhejiang UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

paclitaxel + trastuzumab

docetaxel + trastuzumab

Arm Description

paclitaxel × 12, every week a cycle, trastuzumab × 4, every 3 weeks a cycle; followed by trastuzumab, every 3 weeks a cycle for 9 months. Paclitaxel i.v. 80mg/m2, trastuzumab i.v. loading dose of 8 mg/kg, followed by 6mg/kg

(docetaxel + trastuzumab) × 4, every 3 weeks a cycle; followed by trastuzumab, every 3 weeks a cycle for 9 months. Docetaxel i.v. 100mg/m2, trastuzumab i.v. loading dose of 8 mg/kg, followed by 6mg/kg

Outcomes

Primary Outcome Measures

disease free survival

Evaluate disease free survival (DFS) in patients with stage I HER2-positive breast cancer treated with adjuvant trastuzumab and docetaxel.

Secondary Outcome Measures

overall survival

Evaluate overall survival (OS) in patients with stage I HER2-positive breast cancer treated with adjuvant trastuzumab and docetaxel.

incidence of grade III/IV neurotoxicity

Evaluate the incidence of grade III/IV neurotoxicity associated with adjuvant docetaxel compared with paclitaxel.

Full Information

NCT ID

NCT05189067

First Posted

December 6, 2021

Last Updated

December 26, 2021

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

1. Study Identification

Unique Protocol Identification Number

NCT05189067

Brief Title

Efficacy and Safety of Adjuvant Docetaxel and Trastuzumab in Stage I HER2-positive Breast Cancer

Official Title

A Single-center, Prospective, Randomized Study of Adjuvant Paclitaxel and Trastuzumab Versus Docetaxel and Trastuzumab in Stage I HER2 Positive Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

November 2021

Overall Recruitment Status

Recruiting

Study Start Date

January 31, 2022 (Anticipated)

Primary Completion Date

January 31, 2025 (Anticipated)

Study Completion Date

June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

Among women with stage I HER2-positive breast cancer, adjuvant weekly paclitaxel plus trastuzumab (PH, qw×12) is one of the standard therapies. However, it is quite inconvenient for patients to received weekly treatment for 12 weeks, which also increased the patients' and social economic burdens. In our study, a prospective, randomized, open-label, single-center clinical study was conducted to compare the efficacy and safety of adjuvant docetaxel plus trastuzumab (TH, q3w×4) and the classic regimen (PH, qw×12) in stage I HER2-positive breast cancer in Chinese population.

Detailed Description

HER2-positive breast cancer accounts for about 20% of invasive breast cancers and was historically associated with poor clinical outcomes. Trastuzumab, a humanized monoclonal antibody that binds HER2, improved the outcomes for patients with HER2-positive breast cancer. Four phase 3 randomized trials (HERA, the North Central Cancer Treatment Group N9831, the National Surgical Adjuvant Breast and Bowel Project B-31 and BCIRG006) involving more than 8000 patients showed that when trastuzumab was administered in combination with or after chemotherapy, the risk of recurrence was decreased by approximately 50% and overall survival improved. For patients with lymph node negative, early stage HER2-positive breast cancer, epirubicin/cyclophosphamide followed by docetaxel/trastuzumab (AC-TH) or docetaxel/carboplatin/trastuzumab (TCbH) adjuvant regimen is still widely used, although a smaller absolute benefit is expected. According to the long-term survival outcome of the Adjuvant Paclitaxel and Trastuzumab (APT) trial, patients with tumors measuring up to 3 cm in greatest dimension, negative axillary lymph node or with only micrometastasis, who received adjuvant paclitaxel 80mg/m2 weekly for 12 times plus 1 year trastuzumab, achieved a 3-year disease free survival (DFS) of 98.5%, 5-year DFS of 96.3%, 7-year DFS of 93.3%. The FDA compared the outcome of APT trial with external controls from previous clinical trials, both DFS and overall survival (OS) were similar. However, weekly regimen is quite inconvenient for patients, which also increased the patients'and social economic burdens in China. Docetaxel, a newly developed taxoid anticancer agent, works a comparable way to paclitaxel. In the clinical trial E1199, early breast cancer patients receiving adjuvant adriamycin and cyclophosphamide (AC) followed by docetaxel every 3 weeks achieved similar outcomes with AC followed weekly paclitaxel. In our study, a prospective, randomized, open-label, single-center clinical study is conducted to compare the efficacy and safety of adjuvant docetaxel plus trastuzumab (TH, q3w×4) and the classic regimen (PH, qw×12) in stage I HER2-positive breast cancer in Chinese population.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HER2-positive Breast Cancer, Adjuvant Therapy

Keywords

Docetaxel, Paclitaxel

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

190 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

paclitaxel + trastuzumab

Arm Type

Active Comparator

Arm Description

Arm Title

docetaxel + trastuzumab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Other Intervention Name(s)

Intervention Description

i.v. 80mg/m^2

Intervention Type

Drug

Intervention Name(s)

Trastuzumab

Other Intervention Name(s)

Intervention Description

i.v. loading dose of 8 mg/kg, followed by 6mg/kg

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Other Intervention Name(s)

Intervention Description

i.v. 100mg/m2

Primary Outcome Measure Information:

Title

disease free survival

Description

Evaluate disease free survival (DFS) in patients with stage I HER2-positive breast cancer treated with adjuvant trastuzumab and docetaxel.

Time Frame

Time of Surgery up to 5 years

Secondary Outcome Measure Information:

Title

overall survival

Description

Evaluate overall survival (OS) in patients with stage I HER2-positive breast cancer treated with adjuvant trastuzumab and docetaxel.

Time Frame

Time of Surgery up to 5 years

Title

incidence of grade III/IV neurotoxicity

Description

Evaluate the incidence of grade III/IV neurotoxicity associated with adjuvant docetaxel compared with paclitaxel.

Time Frame

First Dose of chemotherapy up to 12 months.

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Female aged 18 - 70 years old; The histopathological confirm of invasive breast cancer; HER-2 positive: immuno-histochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) confirmed amplification of erbb2 gene; Tumor must be ≤ 2cm in greatest dimension, negative axillary lymph node or with micrometastasis (axillary nodes with tumor clusters ≤ 0.2cm); No more than 90 days from the patient's most recent breast surgery for this breast cancer; Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1; Adequate bone marrow function: neutrophil ≥ 1500/mm^3, hemoglobin ≥ 9 g/dl, and platelets ≥ 100,000/mm^3; Adequate liver and renal function: creatinine ≤ 1.5 folds of the upper limit of normal value; aspartate aminotransferase and alanine aminotransferase ≤ 1.5 folds of the upper limit of normal value, aspartate aminotransferase and alanine aminotransferase ≤ 2 folds of the upper limit of normal value for patient with Gilbert 's syndrome; Left ventricular ejection fraction (LVEF) ≥ 50%; Willing and able to sign informed consent. Exclusion Criteria: Any of the following due to teratogenic potential of chemotherapy: pregnant women, nursing women, women of childbearing potential who are unwilling to employ adequate contraception; Locally advanced tumors at diagnosis, including tumors fixed to the chest wall, peau d'orange, skin ulcerations/nodules, or clinical inflammatory changes; History of prior chemotherapy in the past 5 years; History of prior trastuzumab therapy; Patients with a history of previous invasive breast cancer; Active, unresolved infection; Prior history of any other malignancy in the past 5 years, except for early stage tumors of the skin or cervix treated with curative intent; Can not tolerate or be allergic to chemotherapy, anti-HER-2 therapy or pharmaceutical materials such as benzyl alcohol; ≥ grade 2 neuropathy; Active cardiac disease: Any prior myocardial infarction (asymptomatic changes on EKG suggestive of old myocardial infarction is not an exclusion); Documented congestive heart failure (CHF); Current use of any therapy specifically for CHF; Current uncontrolled hypertension (diastolic >100 mmHg or systolic > 200 mmHg); Clinically significant pericardial effusion; The antibody of hepatitis C virus, HIV or Treponema pallidum positive; HBsAg positive and hepatitis B virus DNA in peripheral blood ≥ 10^3 copy/mL； Enrollment on other Investigational studies within 30 days; Not allowed by the investigators.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tao Pan

Phone

571-86993267

2311318@zju.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Kaimin Hu

Phone

571-86993267

hukmbdn@zju.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tao Pan

Organizational Affiliation

2nd Affiliated Hospital, School of Medicine, Zhejiang University, China

Official's Role

Principal Investigator

Facility Information:

Facility Name

2nd Affiliated Hospital, School of Medicine, Zhejiang University

City

Hangzhou

State/Province

Zhejiang

ZIP/Postal Code

310000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Tao Pan

Phone

057186993267

2311318@zju.edu.cn

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Efficacy and Safety of Adjuvant Docetaxel and Trastuzumab in Stage I HER2-positive Breast Cancer

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