Herceptin and GM-CSF for Metastatic Breast Cancer

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00429104
• Collaborator: Bayer (Industry)
• Enrollment: 18
• Location: 1
• Arm: 1
• Duration (Months): 87
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Herceptin; Drug: GM-CSF	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of GM-CSF to Overcome Herceptin-Resistant HER-2/Neu-Overexpressing Metastatic Breast Cancer
• Study Start Date: Aug 1, 2002
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

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: Sargramostim Leukine

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Tumor Response (Stable Disease) [2 months]

   Number of participants with response defined as stable disease or better using Response Evaluation Criteria In Solid Tumors (RECIST) at the month 2 evaluation.

Secondary Outcome Measures

1. Duration of Stable Disease [6 Years]

   Stable disease is measured from the start of the treatment until the RECIST criteria for disease progression is met.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	U.T.M.D. Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Bayer

Investigators

• Principal Investigator: Naoto Ueno, MD, PhD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00429104
• Other Study ID Numbers: DM01-0100
• First Posted: Jan 31, 2007
• Last Update Posted: Dec 6, 2012
• Last Verified: Dec 1, 2012

• Keywords provided by M.D. Anderson Cancer Center: Breast Cancer; Carcinoma of the Breast; HER-2/neu Overexpression; Herceptin; Trastuzumab; GM-CSF; Sargramostim; Leukine
• Additional relevant MeSH terms: Breast Neoplasms; Trastuzumab; Sargramostim

Study Results

Participant Flow

Recruitment Details	Recruitment Period of November 2002 to April 2007, all recruited at University of Texas MD Anderson Cancer Center.

Arm/Group Title	HER2+ Metastatic Breast Cancer
Arm/Group Description	Herceptin 4 mg/kg intravenous (IV) Over 90 Minutes + Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) 250 mcg/m^2 subcutaneously
Period Title: Overall Study
STARTED	18
COMPLETED	17
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	HER2+ Metastatic Breast Cancer
Arm/Group Description	Herceptin 4 mg/kg intravenous (IV) Over 90 Minutes + Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) 250 mcg/m^2 subcutaneously
Overall Participants	18
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	48
Sex: Female, Male (Count of Participants)
Female	18 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	18 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was per protocol, and of 18 enrolled, one participant was inevaluable.

Arm/Group Title	HER2+ Metastatic Breast Cancer
Arm/Group Description	Herceptin 4 mg/kg intravenous (IV) Over 90 Minutes + Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) 250 mcg/m^2 subcutaneously
Measure Participants	17
Number [participants]	5 27.8%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was per protocol, and of 18 enrolled, one participant was inevaluable.

Arm/Group Title	HER2+ Metastatic Breast Cancer
Arm/Group Description	Herceptin 4 mg/kg intravenous (IV) Over 90 Minutes + Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) 250 mcg/m^2 subcutaneously
Measure Participants	17
Median (Full Range) [weeks]	15.8

Adverse Events

Time Frame	4 years and 6 months
Arm/Group Title	HER2+ Metastatic Breast Cancer
Arm/Group Description	Herceptin 4 mg/kg intravenous (IV) Over 90 Minutes + Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) 250 mcg/m^2 subcutaneously
All Cause Mortality
	HER2+ Metastatic Breast Cancer
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	HER2+ Metastatic Breast Cancer
	Affected / at Risk (%)	# Events
Total	0/17 (0%)
Other (Not Including Serious) Adverse Events
	HER2+ Metastatic Breast Cancer
	Affected / at Risk (%)	# Events
Total	17/17 (100%)
Eye disorders
Red eye	1/17 (5.9%)
Gastrointestinal disorders
Fever	3/17 (17.6%)
Nausea	2/17 (11.8%)
Vomitting	1/17 (5.9%)
Diarrhea	3/17 (17.6%)
Constipation	1/17 (5.9%)
General disorders
Sore Mouth	2/17 (11.8%)
Fatigue	5/17 (29.4%)
Itchy hands/feet	1/17 (5.9%)
Headache	2/17 (11.8%)
Musculoskeletal and connective tissue disorders
Muscle Pain	4/17 (23.5%)
Nervous system disorders
Numbness	1/17 (5.9%)
Sore finger/toes	1/17 (5.9%)
Skin and subcutaneous tissue disorders
Rash at injection site	7/17 (41.2%)
Skin Rash	6/17 (35.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.