Herceptin and GM-CSF for Metastatic Breast Cancer

Phase II Study of GM-CSF to Overcome Herceptin-Resistant HER-2/Neu-Overexpressing Metastatic Breast Cancer

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).

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Herceptin; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • U.T.M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HER2+ Metastatic Breast Cancer; Herceptin 4 mg/kg IV Over 90 Minutes + GM-CSF 250 mcg/m^2 subcutaneously	Drug: Herceptin; 4 mg/kg IV Over 90 Minutes; Other Names: Trastuzumab; Drug: GM-CSF; 250 mcg/m^2 Subcutaneously; Other Names: Leukine; Sargramostim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Tumor Response (Stable Disease)	Number of participants with response defined as stable disease or better using Response Evaluation Criteria In Solid Tumors (RECIST) at the month 2 evaluation.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Stable Disease	Stable disease is measured from the start of the treatment until the RECIST criteria for disease progression is met.	6 Years

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: Bayer

Publications and helpful links

Helpful Links

• The University of Texas M.D.Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start: August 1, 2002
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: January 29, 2007
• First Submitted That Met QC Criteria: January 30, 2007
• First Posted (Estimate): January 31, 2007

Study Record Updates

• Last Update Posted (Estimate): December 6, 2012
• Last Update Submitted That Met QC Criteria: December 4, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Breast Cancer; Trastuzumab; Herceptin; Sargramostim; GM-CSF; Carcinoma of the Breast; HER-2/neu Overexpression; Leukine
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Trastuzumab; Sargramostim
• Other Study ID Numbers: DM01-0100