Trastuzumab and Vinorelbine in Advanced Breast Cancer

• CTCs [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To describe the number of CTCs and the CTCs characteristics before and after therapy, and to explore the correlation of these findings with response.
• Safety and Tolerability [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  To further characterize the safety and tolerability of trastuzumab and vinorelbine in this patient population.

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.

• Participants will receive two different drugs. Trastuzumab will be administered by vein every 3 weeks. Participants will receive a higher dose of trastuzumab on the first day of treatment followed by a lower dose for subsequent administration. Vinorelbine will be administered by vein once a week.
• Each treatment cycle lasts 3 weeks during which time participants will be receiving Vinorelbine weekly and Trastuzumab every 3 weeks. Participants will continue to receive Vinorelbine weekly and Trastuzumab every 3 weeks as long as their cancer is not growing and they are not experiencing severe side effects.
• Circulating tumor cells (CTCs) will be collected at study entry, at 6 weeks or up to one week prior, and when study treatment is stopped.
• ECHO or MUGA scan is performed at study entry and repeated at 18 weeks and then as needed.
• CT or MRI will be performed at study entry and then repeated every 6 weeks for the first 18 weeks and then every 12 weeks thereafter. A bone scan or CT/MRI scan of the brain will be performed if the doctor determines this is medically necessary.

• Breast Cancer
• Metastatic Breast Cancer

• Drug: trastuzumab
  Administered intravenously every 3 weeks.
• Drug: vinorelbine
  Administered intravenously once a week

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

• Brigham and Women's Hospital
• Beth Israel Deaconess Medical Center
• Massachusetts General Hospital
• Genentech