Clinical trial NCT00169104: Effects of Granulocyte Colony-stimulating Factor (G-CSF), Trastuzumab, and Vinorelbine on Immune Cell Function
Official title: A Phase II Trial of Trastuzumab, Neupogen, and Vinorelbine Investigating the Effects on Immune Function and Clinical Outcomes in Patients With Metastatic Breast Cancer Overexpressing Her-2/Neu
Conditions: Metastatic Breast Cancer
Summary: Trastuzumab or Herceptin is an antibody directed against Her-2. Her-2 is a growth factor receptor which is present on the tumors of 25% of patients with breast cancer. The addition of trastuzumab to chemotherapy has been shown in a randomized clinical trial to increase the response rate to chemotherapy, the duration of response to chemotherapy, and to improve the duration of survival of patients with metastatic breast cancer. The anticancer mechanism of action of trastuzumab is unknown, but it is possible that trastuzumab acts by promoting antibody-dependent cell mediated cytotoxicity (ADCC), or direct killing of cancer cells by immune cells, triggered by antibodies bound to the surface of the cancer cell. G-CSF is a drug which is a growth factor for certain types of immune cells. G-CSF has two favorable effects on ADCC. G-CSF increases the pool of circulating cancer-killing immune cells, and G-CSF increases the strength of binding of cancer-killing immune cells to a specific part of the antibody. Therefore, priming with G-CSF significantly increases the efficiency of ADCC, and four days of treatment with G-CSF has been shown to optimize ADCC in some studies. Recent data from the investigators' laboratory indicates that chemotherapy can augment ADCC directed against tumor cells.
The investigators' hypothesis is that pre-treatment with the drug G-CSF would increase the effectiveness of chemotherapy given with trastuzumab.
Interventions:
description: 5 mcgm/kg daily Monday through Friday weeks 3-14
name: G-CSF
other_name: Neupogen
type: Drug
description: 4 mcgm/kg intravenously (IV) over 90 minutes week 1, then 2 mg/kg IV over 30 minutes weeks 2-14
name: trastuzumab
other_name: Herceptin
type: Drug
description: 25 mg/m2 over 6 minutes IV weekly, weeks 3, 4, 6, 7, 9, 10, 12, 13
name: vinorelbine
other_name: Navelbine
type: Drug
description: 5 mcgm/kg SQ daily for ten days, Monday through Friday of the first two weeks of the study
name: G-CSF
other_name: Neupogen
type: Drug
description: Saline will be given SQ daily for ten days, Monday through Friday of the first two weeks of the study
name: saline placebo
type: Drug
Study arms:
design_group_description: Subjects will receive ten doses of G-CSF at a dose of 5 mcgm/kg daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg IV weeks 3 through 14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13 and G-CSF at 5 mcgm/kg SQ daily Monday through Friday weeks 3-14.
design_group_title: 1
design_group_type: Active Comparator
design_group_description: Subjects will receive ten doses of a placebo injection SQ daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg weeks 3-14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13, and G-CSF at 5 mcgm/kg SQ daily Monday through Fridays weeks 3-14.
design_group_title: 2
design_group_type: Placebo Comparator
Sponsor: Dartmouth-Hitchcock Medical Center
Collaborators: Amgen, Inc.
Drug name mappings:
name: 曲妥珠单抗
lang: CN
name: Trastuzumab
lang: EN
name: トラスツズマブ（遺伝子組換え）
lang: JP
name: 非格司亭 （安进）
lang: CN
name: Filgrastim (Amgen)
lang: EN
name: フィルグラスチム（遺伝子組換え）
lang: JP
name: 长春瑞滨双酒石酸盐
lang: CN
name: Vinorelbine Tartrate
lang: EN
name: ビノレルビン酒石酸塩
lang: JP