Clinical trial · Interventional

Effects of Granulocyte Colony-stimulating Factor (G-CSF), Trastuzumab, and Vinorelbine on Immune Cell Function

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

NCT00169104CI-TRIAL-00033899terminatedPhase 2 / Phase 3Results postedClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Why stopped (as posted): Closed due to achievement of primary study endpoint

Summary

Brief summary (as posted)

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.

Conditions

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Metastatic Breast Cancer	Malignant Breast Neoplasm	CURATED_BROADER	0.78

Interventions

Interventions (4)

Intervention	Type	Mapped drug	Match
G-CSF	Drug	—	UNRESOLVED
saline placebo	Drug	—	UNRESOLVED
trastuzumab	Drug	Trastuzumab	ALIAS
vinorelbine	Drug	Vinorelbine	ALIAS

Design

Arms and outcomes

Arms (2)

type
ACTIVE_COMPARATOR
label
1
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.
interventionNames
1. Drug: G-CSF
2. Drug: trastuzumab
3. Drug: vinorelbine
type
PLACEBO_COMPARATOR
label
2
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.
interventionNames

Eligibility

Eligibility (as posted)

Sex: Female
Minimum age: 18 Years

Show eligibility criteria text

Inclusion Criteria:

* All patients must have pathological confirmation of carcinoma of the breast.
* Patients must have metastatic breast cancer by documented clinical or radiological assessment.
* Immunohistochemical analysis of HER-2/neu expression on paraffin-embedded specimens will be performed. HER-2/neu overexpression will be qualitatively scored as 0, 1+, 2+, or 3+, with 3+ indicating the strongest positivity. Fluorescence In Situ Hybridization (FISH) analyses will also be performed on these patients. Patients with 2+ to 3+ overexpression of HER-2/neu (membranous staining) are eligible, regardless of the results of the FISH analysis.
* Age ≥18 years.
* Karnofsky performance status ≥ 60%.
* Adequate hepatic, renal, and hematologic function.
* Prior treatment with trastuzumab will be allowed.
* All patients must have adequate cardiac function (defined as left ventricular ejection fraction ≥ 45%) documented by echocardiogram or MUGA scan.
* Premenopausal women will be required to have a negative urine or serum pregnancy test and to use an effective form of contraception.
* Patients with a history of brain metastases are permitted as long as it has been at least 30 days since definitive treatment, they are clinically stable and a magnetic resonance imaging scan of the brain demonstrates control of the lesion(s).
* All patients must give written informed consent indicating they are aware of the investigational nature of this treatment, as well as the risks and benefits of this protocol.

Exclusion Criteria:

* No treatment with chemotherapy or trastuzumab will be allowed within four weeks of study entry.
* Prior therapy with vinorelbine.
* Known history of hypersensitivity to trastuzumab, Chinese hamster ovary (CHO) cell proteins, or any component of these products.
* History of current unstable angina, symptomatic congestive heart failure, or myocardial infarction within the last 6 months.
* Pregnant women are excluded.
* History of a known hypersensitivity to E. coli-derived proteins, filgrastim, or any component of the product.

References

Publications (1)

RESULTSchwartz GN, Kaufman PA, Tretter CPG, Arrick BA, Mulrooney TJ, Connelly EM, Mellinger DL, Fisher JL, Ernstoff MS. Vinorelbine and trastuzumab enhance effector cell function in patients with Her-2/neu overexpressing metastatic breast cancer. Breast Cancer Research and Treatment 88 (Suppl 1):S128a, 2004.