Clinical trial NCT00429104: Herceptin and GM-CSF for Metastatic Breast Cancer
Official title: Phase II Study of GM-CSF to Overcome Herceptin-Resistant HER-2/Neu-Overexpressing Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Breast Cancer
Carcinoma of the Breast
HER-2/neu Overexpression
Herceptin
Trastuzumab
GM-CSF
Sargramostim
Leukine
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2007-01-31
Enrollment: 18
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Objectives:

1. To determine the patient's tumor response rate that this protocol will produce.
2. To determine the 1 year progression-free survival that this protocol will produce.

Secondary Objective:

1. To determine whether antibody-dependent cell-mediated cytotoxicity (ADCC) is the mechanism of overcoming Herceptin-resistance by use of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF).

Detailed description: GM-CSF stimulates the immune system and may increase the effectiveness of Herceptin.

Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have a complete medical history and physical exam. This includes blood tests (about 2 tea spoons), and x-rays. Women who are able to have children must have a negative blood or urine pregnancy test.

If you are found to be eligible to take part in this study, you will receive trastuzumab through a vein (IV) every week until the disease gets worse. GM-CSF will be injected under the skin at least once a day until the white blood cell count is stable. GM-CSF will also continue during the course of study until the disease progresses.

You will have further evaluation of your disease by computed tomography-CT scan, bone scan, chest X-ray, etc. at 2, 4, 6, 9, 12, 18, and 24 months after the start of treatment. You will have blood tests (about 2 tea spoons) at least twice a week until the appropriate dose of GM-CSF is found. The dose may increase or decrease depending on the blood test.

You will have blood (about 2 tablespoons) drawn before treatment at the 2nd and 4th month, and if the disease gets worse.

You will be removed from the study if the disease is progressing or severe side effects occur.

This is an investigational study. The FDA has approved trastuzumab and GM-CSF, but their use in this study is experimental. A total of 36 patients will take part in this study. All will be enrolled at UT MD Anderson Cancer Center.

Eligibility criteria: Inclusion Criteria:

1. Histological confirmation of invasive carcinoma of the breast.
2. HER-2/neu overexpression: 3+ by immunohistochemical staining or Fluorescence in situ hybridization (FISH) (+).
3. Stage IV breast cancer with measurable disease.
4. Patient receiving progressive disease after Herceptin plus chemotherapy or Herceptin alone. No more than two Herceptin containing regimens.
5. Zubrod performance status 0 or 1.
6. Adequate hematological parameters (White Blood cells-WBC \> 3,000/mm3, platelet count \> 100,000/mm3), adequate renal function (serum creatinine \< 2.0 mg/dl), adequate liver function (total bilirubin, aspartate aminotransferase (AST or SGOT) or alanine aminotransferase (ALT or SGPT) \< 3 x normal).

Exclusion Criteria:

1. Active Brain metastasis.
2. No measurable disease at the time of registration (e.g. bone only, leptomeningeal disease alone or pleural effusion alone).
3. More than 2 Herceptin containing regimens in metastatic breast cancer.
4. Known history of HIV positive.
5. Chronic active hepatitis or cirrhosis.
6. Symptomatic pulmonary disease.
7. Use of steroid of non-steroidal anti-inflammatory analgesic or Cox-2 inhibitor 1 week prior to registration.

Primary outcomes:
measure: Number of Participants With Tumor Response (Stable Disease)
timeFrame: 2 months
Secondary outcomes:
measure: Duration of Stable Disease
timeFrame: 6 Years
Other outcomes:
Locations:
city: Houston
country: United States
facility: U.T.M.D. Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Naoto Ueno, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: