Clinical trial NCT01185509: Trastuzumab and Vinorelbine in Advanced Breast Cancer
Official title: A Phase II, Single Arm, Open Label Study to Evaluate the Efficacy and Safety of Trastuzumab and Vinorelbine in Advanced Breast Cancer Patients With Human Epidermal Growth Factor-2 (HER2) Negative Primary Tumors and HER2 Positive Circulating Tumor Cells
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Metastatic Breast Cancer
Keywords: HER2 negative
HER2 positive
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Beth Israel Deaconess Medical Center
name: Massachusetts General Hospital
name: Genentech, Inc.
First posted: 2010-08-20
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: The analysis was performed for 2 separate cohorts due to a change in study conduct during the trial (see arm description).
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to see what effects trastuzumab in combination with vinorelbine has on breast cancer when the participant has circulating tumor cells that are positive for the protein called HER2. Trastuzumab is an FDA approved drug that targets HER2. The drug combination of trastuzumab and vinorelbine is an effective treatment for patients with breast cancers that are positive for HER2. This trial seeks to determine if the combination can also benefit participants whose original breast cancer was HER2 negative but whose circulating tumor cells are HER2 positive.

Detailed description: OBJECTIVES:

Primary

* To assess the objective response rate (ORR) of trastuzumab and vinorelbine in patients with metastatic breast cancer with HER2 negative primary tumors and HER2 positive circulating tumor cells.

Secondary

* To describe the number of CTCs and the CTCs characteristics before and after therapy, and to explore the correlation of these findings with response.
* To further characterize the safety and tolerability.
* To evaluate progression-free survival.
* To evaluate clinical benefit rate \[complete response (CR)+partial response (PR)+stable disease (SD)\>24 weeks\].

Exploratory

* To determine the clinical feasibility of high-throughput mutation profiling on circulating tumor cells (CTCs).

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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 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: Clinical Benefit Rate (CBR)
timeFrame: 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).
measure: Progression-Free Survival (PFS)
timeFrame: Disease was evaluated radiologically at baseline, on trt every 6 weeks (wks) for the first 18 wks and then every 12 wks and within 2 wks off-study; Median follow-up was 2.7 months.
measure: Baseline Level of Circulating Tumor Cells (CTCs)
timeFrame: Assessed at baseline
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Ian Krop, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.