A Study of Herceptin (Trastuzumab) in Combination With a Taxane in Participants With HER2-Positive Breast Cancer Who Relapsed After (Neo)Adjuvant Herceptin Treatment

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01301729
• Collaborator: (none)
• Enrollment: 32
• Locations: 17
• Arm: 1
• Duration (Months): 40
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This single arm, open-label study will evaluate the efficacy and safety of Herceptin (trastuzumab) in combination with a taxane as first line therapy in participants with HER2-positive breast cancer who relapsed after neoadjuvant or adjuvant Herceptin treatment. Participants will receive Herceptin (loading dose of 4 mg/kg intravenously [iv], 2 mg/kg iv weekly thereafter) with 6 3-week cycles of either docetaxel (100 mg/m2 iv every 3 weeks) or paclitaxel (90 mg/m2 every week). Herceptin treatment will be continued until disease progression or unacceptable toxicity occurs.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Docetaxel; Drug: Paclitaxel; Drug: Trastuzumab	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Single Arm, Open-Label PhIV Study to Investigate the Effect of First-Line Herceptin (Trastuzumab) in Combination With a Taxane in Patients With Metastatic Breast Cancer Who Relapsed After Receiving (Neo)Adjuvant Herceptin for HER2-Positive Early Breast Cancer
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Trastuzumab Participants with metastatic breast cancer received a loading dose of 4 milligrams per kilograms (mg/kg) of trastuzumab intravenously (IV) followed by 2 mg/kg of trastuzumab IV once a week along with docetaxel 100 milligrams per meter square (mg/m^2), every 3 weeks or paclitaxel 90 mg/m^2 once a week until progression of disease, occurrence of intolerable toxicity, the participant discontinues the study or dies.

Drug: Docetaxel; 100 mg/m2 iv every 3 weeks, 6 cycles (18 weeks); Drug: Paclitaxel; 90 mg/kg iv (+/-10%) every 3 weeks for 6 3-week cycles (18 weeks); Drug: Trastuzumab; 4 mg/kg iv loading dose on Day 1, 2 mg/kg iv on Day 8 and weekly thereafter; Other Names: Herceptin

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [From the date of informed consent to the date of death or progressive disease (up to 28 months)]

   PFS was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 and was defined as the time from the date when the participant signed the informed consent form (ICF) until death or progressive disease (PD). PD was defined as 20% increase in the sum of the longest diameter of target lesions. PFS and associated confidence intervals were calculated using the Kaplan-Meier method.

Secondary Outcome Measures

1. Overall Response Rate [up to 28 months]

   Overall response rate was assessed using RECIST 1.0 and defined as the percentage of participants that achieved a complete response (CR) or a partial response (PR). CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions.

2. Duration of Response [From the time of PR or CR until the date of PD or death (up to 28 months)]

   Duration of response was defined as the time from when a PR or CR was first documented until the date of documented PD or death. CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. PD was defined as 20% increase in the sum of the longest diameter of target lesions.

3. Overall Survival [Time from enrollment to the date of death (up to 28 months)]

   Overall survival was defined as the time from the date of enrollment to the date of death due to any cause.

4. Percentage of Participants With an Adverse Event (AE) [Up to 28 days after last infusion of the study drug (28 months)]

   An AE was defined as any adverse medical event that occurred after the participant used the investigational medicinal product (IMP) or other intervention behaviors specified by the protocol in the clinical trial regardless of relationship to the study treatment.

5. Determination of Biomarkers Indicative for Response (Serum and Tumour Tissue Analyses) [up to 28 months]

6. Clinical Benefit Rate [up to 28 months]

   Clinical benefit rate was assessed according to RECIST 1.0 and defined as the percentage of participants who experienced a CR, PR, or stable disease (SD) for at least 6 months. CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. SD was defined as small changes that do not meet above criteria.

7. Time to Progression [From the date of enrollment until the date of progressive disease (up to 28 months)]

   Time to progression was defined as the time from the date of enrollment until the date of progressive disease.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Female participants , >/= 18 years of age

• Locally recurrent/metastatic breast cancer (relapse in supra- or infraclavicular lymph nodes is regarded as metastatic disease)

• HER2-positive primary disease

• Participants must have received Herceptin in the adjuvant and/or neoadjuvant setting

• Relapsed breast cancer >/= 6 months after discontinuing last drugs of Herceptin and/or chemotherapy in the adjuvant and/or neoadjuvant setting for HER2-positive breast cancer

• Measurable disease according to RECIST 1.0

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Maximum cumulative dose of doxorubicin </= 360 mg/m2 or of epirubicin </= 720 mg/m2 or no prior anthracyclines

• At least 3 weeks after prior surgery or radiotherapy

Exclusion Criteria:

• Pregnant or breastfeeding women

• Previous chemotherapy for metastatic breast cancer (prior endocrine therapy till progressive disease is allowed)

• Pleural effusions, ascites or bone lesions as only manifestation of disease

• Brain metastases

• Invasive malignancy other than metastatic breast cancer

• Inadequate bone marrow, hepatic or renal function

• Prior treatment with anti-HER therapies other than (neo)adjuvant Herceptin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Beijing		China	100021
2		Beijing		China	100071
3		Beijing		China	100142
4		Beijing		China	100730
5		Chengdu		China	610041
6		Guangzhou		China	510060
7		Guangzhou		China	510515
8		Guangzhou		China
9		Hangzhou		China	310009
10		Hangzhou		China	310022
11		Harbin		China	150081
12		Nanjing		China	210009
13		Shanghai		China	200032
14		Shenyang		China	110001
15		Wuhan		China	430022
16		Wuhan		China	430030
17		Zhengzhou		China	450008

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01301729
• Other Study ID Numbers: ML25288
• First Posted: Feb 23, 2011
• Last Update Posted: Dec 29, 2016
• Last Verified: Nov 1, 2016

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

Study Results

Participant Flow

Pre-assignment Detail	A total of 32 participants were enrolled in the study and received study treatment.

Arm/Group Title	Trastuzumab
Arm/Group Description	Participants with metastatic breast cancer received a loading dose of 4 milligrams per kilograms (mg/kg) of trastuzumab intravenously (IV) followed by 2 mg/kg of trastuzumab IV once a week along with docetaxel 100 milligrams per meter square (mg/m^2), every 3 weeks or paclitaxel 90 mg/m^2 once a week until progression of disease, occurrence of intolerable toxicity, the participant discontinues the study or dies.
Period Title: Overall Study
STARTED	32
COMPLETED	28
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Trastuzumab
Arm/Group Description	Participants with metastatic breast cancer received a loading dose of 4 milligrams per kilograms (mg/kg) of trastuzumab intravenously (IV) followed by 2 mg/kg of trastuzumab IV once a week along with docetaxel 100 milligrams per meter square (mg/m^2), every 3 weeks or paclitaxel 90 mg/m^2 once a week until progression of disease, occurrence of intolerable toxicity, the participant discontinues the study or dies.
Overall Participants	32
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.5 (11.61)
Gender (Count of Participants)
Female	32 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 and was defined as the time from the date when the participant signed the informed consent form (ICF) until death or progressive disease (PD). PD was defined as 20% increase in the sum of the longest diameter of target lesions. PFS and associated confidence intervals were calculated using the Kaplan-Meier method.
Time Frame	From the date of informed consent to the date of death or progressive disease (up to 28 months)

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) data set is defined as all the participants who are eligible through screening, register and enter the study.

Arm/Group Title	Trastuzumab
Arm/Group Description	Participants with metastatic breast cancer received a loading dose of 4 milligrams per kilograms (mg/kg) of trastuzumab intravenously (IV) followed by 2 mg/kg of trastuzumab IV once a week along with docetaxel 100 milligrams per meter square (mg/m^2), every 3 weeks or paclitaxel 90 mg/m^2 once a week until progression of disease, occurrence of intolerable toxicity, the participant discontinues the study or dies.
Measure Participants	32
Median (95% Confidence Interval) [months]	9.9

2. Secondary Outcome

Title	Overall Response Rate
Description	Overall response rate was assessed using RECIST 1.0 and defined as the percentage of participants that achieved a complete response (CR) or a partial response (PR). CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions.
Time Frame	up to 28 months

Outcome Measure Data

Analysis Population Description

ITT data set is defined as all the participants who are eligible through screening, register and enter the study.

Arm/Group Title	Tastuzumab
Arm/Group Description	Participants with metastatic breast cancer received a loading dose of 4 milligrams per kilograms (mg/kg) of trastuzumab intravenously (IV) followed by 2 mg/kg of trastuzumab IV once a week along with docetaxel 100 milligrams per meter square (mg/m^2), every 3 weeks or paclitaxel 90 mg/m^2 once a week until progression of disease, occurrence of intolerable toxicity, the participant discontinues the study or dies.
Measure Participants	32
Number (95% Confidence Interval) [percentage of participants]	81.3 254.1%

3. Secondary Outcome

Title	Duration of Response
Description	Duration of response was defined as the time from when a PR or CR was first documented until the date of documented PD or death. CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. PD was defined as 20% increase in the sum of the longest diameter of target lesions.
Time Frame	From the time of PR or CR until the date of PD or death (up to 28 months)

Outcome Measure Data

Analysis Population Description

ITT data set is defined as all the participants who are eligible through screening, register and enter the study. Here, number of participants are the participants who had response.

Arm/Group Title	Trastuzumab
Arm/Group Description	Participants with metastatic breast cancer received a loading dose of 4 milligrams per kilograms (mg/kg) of trastuzumab intravenously (IV) followed by 2 mg/kg of trastuzumab IV once a week along with docetaxel 100 milligrams per meter square (mg/m^2), every 3 weeks or paclitaxel 90 mg/m^2 once a week until progression of disease, occurrence of intolerable toxicity, the participant discontinues the study or dies.
Measure Participants	26
Median (95% Confidence Interval) [months]	9.8

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival was defined as the time from the date of enrollment to the date of death due to any cause.
Time Frame	Time from enrollment to the date of death (up to 28 months)

Outcome Measure Data

Analysis Population Description

ITT data set is defined as all the participants who are eligible through screening, register and enter the study.

Arm/Group Title	Trastuzumab
Arm/Group Description	Participants with metastatic breast cancer received a loading dose of 4 milligrams per kilograms (mg/kg) of trastuzumab intravenously (IV) followed by 2 mg/kg of trastuzumab IV once a week along with docetaxel 100 milligrams per meter square (mg/m^2), every 3 weeks or paclitaxel 90 mg/m^2 once a week until progression of disease, occurrence of intolerable toxicity, the participant discontinues the study or dies.
Measure Participants	32
Median (95% Confidence Interval) [months]	NA

5. Secondary Outcome

Title	Percentage of Participants With an Adverse Event (AE)
Description	An AE was defined as any adverse medical event that occurred after the participant used the investigational medicinal product (IMP) or other intervention behaviors specified by the protocol in the clinical trial regardless of relationship to the study treatment.
Time Frame	Up to 28 days after last infusion of the study drug (28 months)

Outcome Measure Data

Analysis Population Description

Safety population is defined as all enrolled participants and have taken at least one dose of study drug.

Arm/Group Title	Trastuzumab
Arm/Group Description	Participants with metastatic breast cancer received a loading dose of 4 milligrams per kilograms (mg/kg) of trastuzumab intravenously (IV) followed by 2 mg/kg of trastuzumab IV once a week along with docetaxel 100 milligrams per meter square (mg/m^2), every 3 weeks or paclitaxel 90 mg/m^2 once a week until progression of disease, occurrence of intolerable toxicity, the participant discontinues the study or dies.
Measure Participants	32
Number [percentage of participants]	93.8 293.1%

6. Secondary Outcome

Title	Determination of Biomarkers Indicative for Response (Serum and Tumour Tissue Analyses)
Time Frame	up to 28 months

Outcome Measure Data

Analysis Population Description

Biomarker analysis was not performed as the eligible biomarker sample quantity was too limited for testing.

Arm/Group Title	Trastuzumab
Arm/Group Description	Participants with metastatic breast cancer received a loading dose of 4 milligrams per kilograms (mg/kg) of trastuzumab intravenously (IV) followed by 2 mg/kg of trastuzumab IV once a week along with docetaxel 100 milligrams per meter square (mg/m^2), every 3 weeks or paclitaxel 90 mg/m^2 once a week until progression of disease, occurrence of intolerable toxicity, the participant discontinues the study or dies.
Measure Participants	0

7. Secondary Outcome

Title	Clinical Benefit Rate
Description	Clinical benefit rate was assessed according to RECIST 1.0 and defined as the percentage of participants who experienced a CR, PR, or stable disease (SD) for at least 6 months. CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. SD was defined as small changes that do not meet above criteria.
Time Frame	up to 28 months

Outcome Measure Data

Analysis Population Description

ITT data set is defined as all the participants who are eligible through screening, register and enter the study.

Arm/Group Title	Trastuzumab
Arm/Group Description	Participants with metastatic breast cancer received a loading dose of 4 milligrams per kilograms (mg/kg) of trastuzumab intravenously (IV) followed by 2 mg/kg of trastuzumab IV once a week along with docetaxel 100 milligrams per meter square (mg/m^2), every 3 weeks or paclitaxel 90 mg/m^2 once a week until progression of disease, occurrence of intolerable toxicity, the participant discontinues the study or dies.
Measure Participants	32
Number (95% Confidence Interval) [percentage of participants]	81.3 254.1%

8. Secondary Outcome

Title	Time to Progression
Description	Time to progression was defined as the time from the date of enrollment until the date of progressive disease.
Time Frame	From the date of enrollment until the date of progressive disease (up to 28 months)

Outcome Measure Data

Analysis Population Description

ITT data set is defined as all the participants who are eligible through screening, register and enter the study.

Arm/Group Title	Trastuzumab
Arm/Group Description	Participants with metastatic breast cancer received a loading dose of 4 milligrams per kilograms (mg/kg) of trastuzumab intravenously (IV) followed by 2 mg/kg of trastuzumab IV once a week along with docetaxel 100 milligrams per meter square (mg/m^2), every 3 weeks or paclitaxel 90 mg/m^2 once a week until progression of disease, occurrence of intolerable toxicity, the participant discontinues the study or dies.
Measure Participants	32
Median (95% Confidence Interval) [months]	9.9

Adverse Events

Time Frame	Up to 28 days after the last dose of the study drug (up to 28 months)
Adverse Event Reporting Description	An AE was defined as any adverse medical event that occurred after the participant used the investigational medicinal product (IMP) or other intervention behaviors specified by the protocol in the clinical trial regardless of relationship to the study treatment.
Arm/Group Title	Trastuzumab
Arm/Group Description	Participants with metastatic breast cancer received a loading dose of 4 milligrams per kilograms (mg/kg) of trastuzumab intravenously (IV) followed by 2 mg/kg of trastuzumab IV once a week along with docetaxel 100 milligrams per meter square (mg/m^2), every 3 weeks or paclitaxel 90 mg/m^2 once a week until progression of disease, occurrence of intolerable toxicity, the participant discontinues the study or dies.
All Cause Mortality
	Trastuzumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Trastuzumab
	Affected / at Risk (%)	# Events
Total	5/32 (15.6%)
Blood and lymphatic system disorders
Leukopenia	1/32 (3.1%)
Neutropenia	1/32 (3.1%)
Eye disorders
Cataract	1/32 (3.1%)
Infections and infestations
Infection	1/32 (3.1%)
Upper respiratory tract infection	1/32 (3.1%)
Psychiatric disorders
Completed suicide	1/32 (3.1%)
Other (Not Including Serious) Adverse Events
	Trastuzumab
	Affected / at Risk (%)	# Events
Total	29/32 (90.6%)
Blood and lymphatic system disorders
Leukopenia	19/32 (59.4%)
Neutropenia	18/32 (56.3%)
Agranulocytosis	10/32 (31.3%)
Bone marrow failure	3/32 (9.4%)
Anaemia	3/32 (9.4%)
Thrombocytopenia	2/32 (6.3%)
Gastrointestinal disorders
Diarrhoea	5/32 (15.6%)
Hypophagia	5/32 (15.6%)
Vomting	4/32 (12.5%)
Nausea	3/32 (9.4%)
Constipation	2/32 (6.3%)
Mouth ulceration	2/32 (6.3%)
General disorders
Asthenia	7/32 (21.9%)
Pyrexia	6/32 (18.8%)
Oedema peripheral	5/32 (15.6%)
Flushing	2/32 (6.3%)
Face oedema	2/32 (6.3%)
Injury, poisoning and procedural complications
Neurotoxicity	4/32 (12.5%)
Investigations
Alanine aminotransferase increased	4/32 (12.5%)
Aspartate aminotransferase increased	3/32 (9.4%)
Transaminases increased	2/32 (6.3%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	3/32 (9.4%)
Nervous system disorders
Hypoaesthesia	11/32 (34.4%)
Headache	3/32 (9.4%)
Insomnia	2/32 (6.3%)
Respiratory, thoracic and mediastinal disorders
Cough	4/32 (12.5%)
Chest discomfort	3/32 (9.4%)
Nasopharyngitis	2/32 (6.3%)
Skin and subcutaneous tissue disorders
Alopecia	7/32 (21.9%)
Nail disorder	5/32 (15.6%)
Rash	3/32 (9.4%)
Pigmentation disorder	3/32 (9.4%)
Paronychia	2/32 (6.3%)

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.