Vinflunine Plus Trastuzumab in Human Epidermal Growth Factor Receptor 2 (HER2neu) Over-Expressing Metastatic Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT00284180
First received: January 27, 2006
Last updated: July 9, 2013
Last verified: July 2013
  Purpose

This research study involves the anti-cancer medication trastuzumab and the investigational drug vinflunine. The purpose of this trials is to see if trastuzumab and vinflunine used in combination or vinflunine alone is effective in the treatment of metastatic breast cancer


Condition Intervention Phase
Breast Neoplasms
Breast Cancer
Drug: Vinflunine
Drug: Trastuzumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Vinflunine Plus Trastuzumab in Human Epidermal Growth Factor Receptor 2 (HER2neu) Over-Expressing Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.


Enrollment: 32
Study Start Date: January 2006
Study Completion Date: November 2010
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HER2 Negative Intervention
Vinflunine 320 mg/m2 intravenously day 1 over 20 minutes, repeated every 21 days
Drug: Vinflunine
Novel second generation vinca alkaloid
Other Name: Javlor
Experimental: HER2 Positive Intervention
Vinflunine 280 mg/m2 every 21 days with trastuzumab administered with a loading dose of 8 mg/kg, followed by 6 mg/kg IV on day 1 of each subsequent cycle, repeated every 21 days. If no grade 3/4 adverse events were encountered after the first cycle of vinflunine/trastuzumab, the dose of vinflunine could be escalated to 320 mg/m2.
Drug: Vinflunine
Novel second generation vinca alkaloid
Other Name: Javlor
Drug: Trastuzumab
Anti-HER2 monoclonal antibody
Other Name: Herceptin

Detailed Description:

If the tumor is HER2neu positive, eligible patients will receive trastuzumab and vinflunine intravenously (IV) every 3 weeks.

If the tumor is HER2neu negative, eligible patients will receive vinflunine intravenously (IV) every 3 weeks.

Patients whose cancer does not grow or decreases in size may continue to receive treatment until cancer progression. Evaluation of cancer will be every 9 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed breast cancer with metastatic disease. Patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
  • The human epidermal growth factor receptor 2 (HER2) status of the tumor will be used to stratify patients. Tumors that are HER2 FISH+ will receive vinflunine and trastuzumab. Patients with tumors which are HER2 FISH negative or if the HER2 status is unknown/not performed will remain on study and will receive single agent vinflunine.
  • Patients must have measurable disease not directly irradiated as per RECIST criteria.
  • Measurable disease- is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.
  • Prior Therapy: Patients must not have received prior chemotherapy in the metastatic breast setting. Patients who have not received prior anthracyclines or taxanes should be considered for these agents. Patients may have received prior chemotherapy and/or hormonal therapy for early stage breast cancer. The chemotherapy regimen may have included an anthracycline and/or a taxane as long as it has been > 6 months since completion of the regimen. Adjuvant trastuzumab is allowed. Patients may have received prior radiation therapy in either the metastatic or early stage setting as long as <25% of the bone marrow has been treated. Prior radiation to the whole pelvis is not allowed. Radiation therapy must be completed at least 7 days prior to study registration, and all radiation related toxicities must be resolved to grade ≤ 1 before patient is eligible for study inclusion. Patients may have received any number of hormonal therapies in the neo-adjuvant, adjuvant or metastatic setting.
  • Age >18 years.
  • Life expectancy of > 6 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status <2.
  • Patients must have normal organ and marrow function. Laboratory tests should be completed within 14 days prior to starting study treatment. Only for patients who will be receiving trastuzumab, a left ventricular ejection fraction (LVEF) may be determined by either echocardiography or multigated acquisition (MUGA) scan, and should be obtained within 4 weeks prior to starting study treatment.
  • Fertility/reproduction. Patients must not be pregnant, expect to become pregnant or conceive a child from time of first signing study consent until at least 12 weeks after last dose of study treatment.

Exclusion Criteria

  • Patients who have received prior vinca alkaloid chemotherapy are not eligible unless treatment was completed > 5 years ago.
  • Patients in which the HER2 status is unknown or is FISH negative will not receive trastuzumab but are eligible for treatment with single agent vinflunine.
  • Patients that have received prior chemotherapy for metastatic breast cancer.
  • Patients receiving trastuzumab must have received a cumulative dose of doxorubicin less than 360mg/m2, and/or an epirubicin cumulative dose less than 720mg/m2 for study entry.
  • Patients with known leptomeningeal carcinomatosis are excluded from this clinical trial
  • History of grade 3 or 4 allergic reactions attributed to trastuzumab.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study
  • History of other non-breast cancer malignancy except for carcinoma in situ of the cervix or non-melanoma skin cancer, or in patients with greater than a 5-year disease free interval from a prior malignancy.
  • Patients who have received prior chemotherapy for early stage breast cancer with the completion of the regimen being < 6 months will not be eligible.
  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: NCT00284180

Locations
United States, Alabama
Northeast Alabama Regional Medical Center
Anniston, Alabama, United States, 36207
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
Integrated Community Oncology Network
Jacksonville, Florida, United States, 32256
Watson Clinic Center for Cancer Care and Research
Lakeland, Florida, United States, 33805
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Louisiana
Hematology Oncology Life Center
Alexandria, Louisiana, United States, 71301
United States, Michigan
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, South Carolina
Spartanburg Regional Medical Center
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
Associates in Hematology Oncology
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology
Nashville, Tennessee, United States, 37205
Sponsors and Collaborators
SCRI Development Innovations, LLC
Bristol-Myers Squibb
Investigators
Principal Investigator: Denise A Yardley, MD SCRI Development Innovations, LLC
  More Information

Additional Information:
Publications:
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00284180     History of Changes
Other Study ID Numbers: SCRI BRE 89
Study First Received: January 27, 2006
Results First Received: March 25, 2013
Last Updated: July 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Breast Neoplasms
Breast Cancer
Vinflunine
Vinca Alkaloid
Javlor

Additional relevant MeSH terms:
Neoplasms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Mitogens
Trastuzumab
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014