Trastuzumab and Vinorelbine in Advanced Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Dana-Farber Cancer Institute
Sponsor:
Collaborators:
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
Genentech
Information provided by (Responsible Party):
Ian E. Krop, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01185509
First received: August 18, 2010
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Metastatic Breast Cancer
Drug: trastuzumab
Drug: vinorelbine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 HER2 Negative Primary Tumors and HER2 Positive Circulating Tumor Cells

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Objective Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess the objective response rate of trastuzumab and vinorelbine in patients with metastatic breast cancer with HER2 negative primary tumors and HER2 positive circulating cells.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 35
Study Start Date: October 2010
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: trastuzumab
    Administered intravenously every 3 weeks.
    Drug: vinorelbine
    Administered intravenously once a week
Detailed Description:
  • 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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01185509

Contacts
Contact: Ian Krop, MD, PhD 617-632-3800 ian_krop@dfci.harvard.edu

Locations
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Ian Krop, MD, PhD         
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02115
Sub-Investigator: Gerburg Wulf, MD, PhD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Sub-Investigator: Steven Isakoff, MD, PhD         
Dana-Farber Cancer Institute at Faulkner Hospital Active, not recruiting
Boston, Massachusetts, United States, 02130
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
Genentech
Investigators
Principal Investigator: Ian Krop, MD, PhD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Ian E. Krop, MD, PhD, Assistant Professor of Medicine, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01185509     History of Changes
Other Study ID Numbers: 10-207, H4913s
Study First Received: August 18, 2010
Last Updated: April 30, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
HER2 negative
HER2 positive

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Vinorelbine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on October 01, 2014