Trastuzumab and Vinorelbine in Advanced Breast Cancer | NCT01185509

NCT01185509

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
H4913s	Other Identifier	Genentech, Inc

Status Module

Name	Class
Brigham and Women's Hospital	OTHER
Beth Israel Deaconess Medical Center	OTHER
Massachusetts General Hospital	OTHER
Genentech, Inc.

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Trastuzumab and Vinorelbine - Cohort A	Experimental	Cycle 1: Patients received trastuzumab 8 mg/kg intravenously (IV) on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Cycles 2+: Patients received trastuzumab 6 mg/kg IV on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Patients were treated until disease progression or unacceptable toxicity. Eligibility required patients to have HER2 amplification by fluorescence in situ hybridization (FISH) (mean ratio > 2.0). The CTC tests of the first 11 patients were done at DFCI. The study team then decided to proceed with a different CTC test performed outside of DFCI. Because the method of CTC isolation was different from that performed by DFCI, the first 11 patients were placed into a separate cohort (Cohort A) and the remaining 20 patients represented the main cohort.	Drug: trastuzumab Drug: vinorelbine
Trastuzumab and Vinorelbine - Main Cohort	Experimental	Cycle 1: Patients received trastuzumab 8 mg/kg intravenously (IV) on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Cycles 2+: Patients received trastuzumab 6 mg/kg IV on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Patients were treated until disease progression or unacceptable toxicity. Eligibility required patients to have HER2 amplification by FISH (mean ratio > 2.0). The CTC tests of the first 11 patients were done at DFCI. The study team then decided to proceed with a different CTC test performed outside of DFCI. Because the method of CTC isolation was different from that performed by DFCI, the first 11 patients were placed into a separate cohort (Cohort A) and the remaining 20 patients represented the main cohort.	Drug: trastuzumab Drug: vinorelbine

Name	Type	Description	Arm Group Labels	Other Names
trastuzumab	Drug		Trastuzumab and Vinorelbine - Cohort A Trastuzumab and Vinorelbine - Main Cohort
vinorelbine

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as the percentage of patients achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.	Disease was evaluated radiologically at baseline, on trt every 6 weeks (wks) for the first 18 wks and then every 12 wks; Median (range) trt duration was 12 weeks (3-67).

Secondary Outcomes

Measure	Description	Time Frame
Clinical Benefit Rate (CBR)	CBR was defined as achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria. SD needed to be a minimum 24 weeks in duration

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically or cytologically confirmed metastatic invasive mammary carcinoma. The primary cancer must be HER2 negative by fluorescence in situ hybridization and/or immunohistochemistry.
Patients must have CTCs with HER2 amplification by FISH.
Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as 20mm or greater with conventional techniques of as 10mm or greater with spiral CT scan.
Study participants must have either archival primary tumor or metastatic tumor tissue available to allow analysis to confirm their HER2 status.
Patients must have received at least 1 prior chemotherapy regimen for metastatic breast cancer or evidence of disease progression within 6 months of completing adjuvant chemotherapy. Patients can receive any number of biological or hormonal regimens and remain eligible.
18 years of age or older
Life expectancy of greater than 3 months
ECOG Performance Status of 0, 1 or 2
Normal organ and marrow function as outlined in the protocol
Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.

Exclusion Criteria:

Participants must have recovered from all reversible toxicities related to prior therapy before beginning protocol treatment, and may not have any pre-existing treatment-related toxicities in excess of grade 2
Participants may not be receiving any other investigational agents while participating in this study
Participants may not have received trastuzumab or vinorelbine in the past
Participants receiving any medications or substances that are inhibitors of cytochrome P450 isoenzymes in the CYP3A subfamily are ineligible.
EKG abnormalities of known clinical significance, such as prolonged QT.
Left ventricular ejection fraction < 50%
Patients with peripheral neuropathy of any etiology that exceeds grade 1 are ineligible
Uncontrolled intercurrent illness
Individuals with symptomatic or progressive brain metastases are ineligible. Subjects with treated brain metastases are eligible if they have no radiographic or other signs of progression in the brain for 1 month or longer after completion of local therapy. Any corticosteroid use for brain metastases must have been discontinued without subsequent appearance of symptoms for more than 4 weeks prior to study treatment.
Individuals with active second malignancy are ineligible. Patients that are disease-free from a previously treated non-breast malignancy and have a 20% or less chance of recurrence are eligible.
Pregnant or breast feeding women
HIV-positive individuals on combination antiretroviral therapy

Name	Affiliation	Role
Ian Krop, MD, PhD	Dana-Farber Cancer Institute	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Massachusetts General Hospital		Boston	Massachusetts	02114	United States
Beth Israel Deaconess Medical Center

PubMed Identifier	Type	Citation	Retractions
34994617	Derived	Parsons HA, Macrae ER, Guo H, Li T, Barry WT, Tayob N, Wulf GM, Isakoff SJ, Krop IE. Phase II Single-Arm Study to Assess Trastuzumab and Vinorelbine in Advanced Breast Cancer Patients With HER2-Negative Tumors and HER2-Positive Circulating Tumor Cells. JCO Precis Oncol. 2021 Nov;5:896-903. doi: 10.1200/PO.20.00461.

Arm/Group Information

ID	Title	Description
FG000	Trastuzumab and Vinorelbine - Cohort A	Cycle 1: Patients received trastuzumab 8 mg/kg intravenously (IV) on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Cycles 2+: Patients received trastuzumab 6 mg/kg IV on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Patients were treated until disease progression or unacceptable toxicity. Eligibility required patients to have HER2 amplification by FISH (mean ratio > 2.0). The CTC tests of the first 11 patients were done at DFCI. The study team then decided to proceed with a different CTC test performed outside of DFCI. Because the method of CTC isolation was different from that performed by DFCI, the first 11 patients were placed into a separate cohort (Cohort A) and the remaining 20 patients represented the main cohort.
FG001	Trastuzumab and Vinorelbine - Main Cohort	Cycle 1: Patients received trastuzumab 8 mg/kg intravenously (IV) on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Cycles 2+: Patients received trastuzumab 6 mg/kg IV on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Patients were treated until disease progression or unacceptable toxicity. Eligibility required patients to have HER2 amplification by FISH (mean ratio > 2.0). The CTC tests of the first 11 patients were done at DFCI. The study team then decided to proceed with a different CTC test performed outside of DFCI. Because the method of CTC isolation was different from that performed by DFCI, the first 11 patients were placed into a separate cohort (Cohort A) and the remaining 20 patients represented the main cohort.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Trastuzumab and Vinorelbine - Cohort A	Cycle 1: Patients received trastuzumab 8 mg/kg intravenously (IV) on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Cycles 2+: Patients received trastuzumab 6 mg/kg IV on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Patients were treated until disease progression or unacceptable toxicity. Eligibility required patients to have HER2 amplification by FISH (mean ratio > 2.0). The CTC tests of the first 11 patients were done at DFCI. The study team then decided to proceed with a different CTC test performed outside of DFCI. Because the method of CTC isolation was different from that performed by DFCI, the first 11 patients were placed into a separate cohort (Cohort A) and the remaining 20 patients represented the main cohort.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Median

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Objective Response Rate (ORR)

ORR was defined as the percentage of patients achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

The analysis dataset is comprised of all treated patients.

Posted

Number

95% Confidence Interval

percentage of patients

Disease was evaluated radiologically at baseline, on trt every 6 weeks (wks) for the first 18 wks and then every 12 wks; Median (range) trt duration was 12 weeks (3-67).

ID	Title	Description
OG000	Trastuzumab and Vinorelbine - Cohort A

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Trastuzumab and Vinorelbine - Cohort A	Cycle 1: Patients received trastuzumab 8 mg/kg intravenously (IV) on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Cycles 2+: Patients received trastuzumab 6 mg/kg IV on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Patients were treated until disease progression or unacceptable toxicity. Eligibility required patients to have HER2 amplification by FISH (mean ratio > 2.0). The CTC tests of the first 11 patients were done at DFCI. The study team then decided to proceed with a different CTC test performed outside of DFCI. Because the method of CTC isolation was different from that performed by DFCI, the first 11 patients were placed into a separate cohort (Cohort A) and the remaining 20 patients represented the main cohort.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Abdominal infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Abdominal pain	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment

Title	Organization	Phone	Extension	Email
Ian Krop, MD, PhD	Dana-Farber Cancer Institute	617.632.6973		Ian_Krop@dfci.harvard.edu

ID	Term
D001943	Breast Neoplasms

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases

ID	Term
D000068878	Trastuzumab
D000077235	Vinorelbine

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins

Cycle 1: Patients received trastuzumab 8 mg/kg intravenously (IV) on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Cycles 2+: Patients received trastuzumab 6 mg/kg IV on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Patients were treated until disease progression or unacceptable toxicity. Eligibility required patients to have HER2 amplification by FISH (mean ratio > 2.0). The CTC tests of the first 11 patients were done at DFCI. The study team then decided to proceed with a different CTC test performed outside of DFCI. Because the method of CTC isolation was different from that performed by DFCI, the first 11 patients were placed into a separate cohort (Cohort A) and the remaining 20 patients represented the main cohort.