Phase 2 Study of Trastuzumab and Etoposide for Her2 Positive Breast Cancer

• Sponsor: Medstar Health Research Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00810017
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 2
• Location: 1
• Arm: 1
• Duration (Months): 15.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is for women and men who have previously treated metastatic (has spread to other parts in the body), Her2- positive breast cancer. The purpose of this study is to find out what effects (good and bad) the FDA-approved drugs etoposide and trastuzumab have on this type of breast cancer and to determine if these drugs are safe to use together. This research is being done to find more effective treatment for this type of condition.

In this study, trastuzumab and etoposide will be given by intravenous infusion (IV; through a vein) on the first 3 days of every 3-week cycle. This is repeated for 6 cycles. After 6 cycles, only trastuzumab will be given until worsening of disease. In this study, a small amount of your tissue that was collected when you had surgery will be evaluated in the lab to look at genetic differences among people and how those differences may affect a response to a specific drug or medicine. This testing will look for a gene called Top2A. Previous studies suggest that people who have both the Top2A and Her2 genes respond to certain chemotherapies (anti-cancer drugs) differently from those who only have the Her2 gene.

Condition or Disease	Intervention/Treatment	Phase
HER-2 Positive Metastatic Breast Cancer	Drug: Etoposide; Drug: Trastuzumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Clinical Study Combining Trastuzumab With Etoposide in Treatment of HER2-Positive Metastatic Breast Cancer.
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single arm study Etoposide 100mg/m2 daily x 3 days Q3W and Trastuzumab 8mg/kg loading dose then 6mg/kg, then single agent until disease progression	Drug: Etoposide; etoposide 100 mg/m2 daily for 3 days every three weeks for 6 cycles; Other Names: Eposin Etopophos Vepesid VP-16 ; Drug: Trastuzumab; intravenous trastuzumab 8 mg/kg loading dose and then 6 mg/kg every three weeks and then single agent trastuzumab until progression of disease; Other Names: Herceptin

Outcome Measures

Primary Outcome Measures

1. To Determine ORR of Trastuzumab Combined With Etoposide in Patients With HER2 Positive Metastatic Breast Cancer, and to Assess Toxicity of the Combination of Trastuzumab With Intravenous Etoposide. [The best overall response is the best response recorded from the start of first treatment until the date of first progression or date of death from any cause whichever came first, assessed up to 24 months]

   To determine the overall response rate

2. To Determine Efficacy of Trastuzumab Combined With Etoposide in Patients With HER2-positive Metastatic Breast Cancer, and to Assess Toxicity of the Combination of Trastuzumab With Intravenous Etoposide. [From the start of first treatment until unacceptable toxicity or date of death, whichever came first, over 24 months]

   Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Secondary Outcome Measures

1. Determine Duration of Response [Stable disease is measured from the start of the treatment until the criteria for progression are met, assessed by CT scans at a minimum interval of 8 weeks over 5 years]

   Stable disease

2. Determine Duration of Response [Time to disease progression is defined as time from registration date to the date of documented disease progression or death on study, whichever occurs first for 5 years]

   Time to disease progression

3. Determine Duration of Response [The progression-free survival rate is defined as the percentage of patients who are without disease progression while on the study treatment at the end of study, over 5 years]

   The duration of overall response will be measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started. The duration of overall CR is measured from the time measurements are met for CR until the first date that recurrent disease is objectively documented

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Females or males with histologic confirmation of breast carcinoma and diagnosis of metastatic breast adenocarcinoma

• Confirmed HER2 amplification by immunohistochemical staining (IHC) 3+ or FISH amplified (either primary or metastatic).

• Have had any number of prior HER2 targeted therapy containing chemotherapies for treatment of breast cancer

• Measurable extent of disease

• Life expectancy of 3 months or greater

• Patients must have adequate heart function, determined with ECHO or MUGA (ECHO preferred).

• Patients must have adequate bone marrow and organ function

• Patient of childbearing potential must be willing to use an effective means of contraception during their participation on trial

• Greater than 3 weeks from prior radiation or chemotherapy; more than 1 week from prior hormonal therapy; and more than 6 weeks from prior treatment with nitrosoureas or mitomycin.

• No serious intercurrent medical illness.

• Controlled metastatic CNS disease ≥ 3 months

• The ability to understand and willingness to sign a written informed consent form, and to comply with the protocol.

Exclusion Criteria:

• Pregnant or nursing women

• Patients who are poor medical risk because of other non-malignant systemic disease or active, uncontrolled infection.

• Prior craniospinal radiation, or total body irradiation (TBI).

• Patients receiving G-CSF (filgrastim or pegfilgrastim) or thrombopoietin (or other platelet growth factors) within the 3 weeks prior to enrollment (erythropoietin is allowed).

• Prior chemotherapy within the last 3 weeks (last 6 weeks for nitrosureas/mitomycin).

• Prior radiation therapy within the last 3 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation).

• Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.

• Current symptoms of angina or uncontrolled arrhythmias, uncontrolled hypertension with systolic blood pressure >=170 or diastolic blood pressure >=110.

• Psychiatric illness precluding participation in study

• Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest.

• Carcinomatous meningitis or CNS mets not controlled for ≥ 3 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington Cancer Institute	Washington	District of Columbia	United States	20010

Sponsors and Collaborators

• Medstar Health Research Institute
• Genentech, Inc.

Investigators

• Principal Investigator: Sandra M Swain, MD, Medstar Health Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medstar Health Research Institute
• ClinicalTrials.gov Identifier: NCT00810017
• Other Study ID Numbers: IIT_H446Us
• First Posted: Dec 17, 2008
• Last Update Posted: May 19, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Medstar Health Research Institute: Her2 Positive; Breast Cancer; Metastatic
• Additional relevant MeSH terms: Breast Neoplasms; Trastuzumab; Etoposide

Study Results

Participant Flow

Arm/Group Title	Single Arm Study
Arm/Group Description	Etoposide 100mg/m2 daily x 3 days Q3W and Trastuzumab 8mg/kg loading dose then 6mg/kg, then single agent until disease progression Etoposide: etoposide 100 mg/m2 daily for 3 days every three weeks for 6 cycles Trastuzumab: intravenous trastuzumab 8 mg/kg loading dose and then 6 mg/kg every three weeks and then single agent trastuzumab until progression of disease
Period Title: Overall Study
STARTED	2
COMPLETED	0
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Single Arm Study
Arm/Group Description	Etoposide 100mg/m2 daily x 3 days Q3W and Trastuzumab 8mg/kg loading dose then 6mg/kg, then single agent until disease progression Etoposide: etoposide 100 mg/m2 daily for 3 days every three weeks for 6 cycles Trastuzumab: intravenous trastuzumab 8 mg/kg loading dose and then 6 mg/kg every three weeks and then single agent trastuzumab until progression of disease
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 50%
>=65 years	1 50%
Sex: Female, Male (Count of Participants)
Female	2 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%

Outcome Measures

1. Primary Outcome

Title	To Determine ORR of Trastuzumab Combined With Etoposide in Patients With HER2 Positive Metastatic Breast Cancer, and to Assess Toxicity of the Combination of Trastuzumab With Intravenous Etoposide.
Description	To determine the overall response rate
Time Frame	The best overall response is the best response recorded from the start of first treatment until the date of first progression or date of death from any cause whichever came first, assessed up to 24 months

Outcome Measure Data

Analysis Population Description

Study was terminated and no results were collected.

Arm/Group Title	Single Arm Study
Arm/Group Description	Etoposide 100mg/m2 daily x 3 days Q3W and Trastuzumab 8mg/kg loading dose then 6mg/kg, then single agent until disease progression Etoposide: etoposide 100 mg/m2 daily for 3 days every three weeks for 6 cycles Trastuzumab: intravenous trastuzumab 8 mg/kg loading dose and then 6 mg/kg every three weeks and then single agent trastuzumab until progression of disease
Measure Participants	0

2. Primary Outcome

Title	To Determine Efficacy of Trastuzumab Combined With Etoposide in Patients With HER2-positive Metastatic Breast Cancer, and to Assess Toxicity of the Combination of Trastuzumab With Intravenous Etoposide.
Description	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame	From the start of first treatment until unacceptable toxicity or date of death, whichever came first, over 24 months

Outcome Measure Data

Analysis Population Description

Study was terminated and no results were collected.

Arm/Group Title	Single Arm Study
Arm/Group Description	Etoposide 100mg/m2 daily x 3 days Q3W and Trastuzumab 8mg/kg loading dose then 6mg/kg, then single agent until disease progression Etoposide: etoposide 100 mg/m2 daily for 3 days every three weeks for 6 cycles Trastuzumab: intravenous trastuzumab 8 mg/kg loading dose and then 6 mg/kg every three weeks and then single agent trastuzumab until progression of disease
Measure Participants	0

3. Secondary Outcome

Title	Determine Duration of Response
Description	Stable disease
Time Frame	Stable disease is measured from the start of the treatment until the criteria for progression are met, assessed by CT scans at a minimum interval of 8 weeks over 5 years

Outcome Measure Data

Analysis Population Description

Study was terminated and no results were collected.

Arm/Group Title	Single Arm Study
Arm/Group Description	Etoposide 100mg/m2 daily x 3 days Q3W and Trastuzumab 8mg/kg loading dose then 6mg/kg, then single agent until disease progression Etoposide: etoposide 100 mg/m2 daily for 3 days every three weeks for 6 cycles Trastuzumab: intravenous trastuzumab 8 mg/kg loading dose and then 6 mg/kg every three weeks and then single agent trastuzumab until progression of disease
Measure Participants	0

4. Secondary Outcome

Title	Determine Duration of Response
Description	Time to disease progression
Time Frame	Time to disease progression is defined as time from registration date to the date of documented disease progression or death on study, whichever occurs first for 5 years

Outcome Measure Data

Analysis Population Description

Study was terminated and no results were collected.

Arm/Group Title	Single Arm Study
Arm/Group Description	Etoposide 100mg/m2 daily x 3 days Q3W and Trastuzumab 8mg/kg loading dose then 6mg/kg, then single agent until disease progression Etoposide: etoposide 100 mg/m2 daily for 3 days every three weeks for 6 cycles Trastuzumab: intravenous trastuzumab 8 mg/kg loading dose and then 6 mg/kg every three weeks and then single agent trastuzumab until progression of disease
Measure Participants	0

5. Secondary Outcome

Title	Determine Duration of Response
Description	The duration of overall response will be measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started. The duration of overall CR is measured from the time measurements are met for CR until the first date that recurrent disease is objectively documented
Time Frame	The progression-free survival rate is defined as the percentage of patients who are without disease progression while on the study treatment at the end of study, over 5 years

Outcome Measure Data

Analysis Population Description

Study was terminated and no results were collected.

Arm/Group Title	Single Arm Study
Arm/Group Description	Etoposide 100mg/m2 daily x 3 days Q3W and Trastuzumab 8mg/kg loading dose then 6mg/kg, then single agent until disease progression Etoposide: etoposide 100 mg/m2 daily for 3 days every three weeks for 6 cycles Trastuzumab: intravenous trastuzumab 8 mg/kg loading dose and then 6 mg/kg every three weeks and then single agent trastuzumab until progression of disease
Measure Participants	0

Adverse Events

Time Frame	Study was terminated and no results were collected.
Adverse Event Reporting Description	Study was terminated and no results were collected.
Arm/Group Title	Single Arm Study
Arm/Group Description	Etoposide 100mg/m2 daily x 3 days Q3W and Trastuzumab 8mg/kg loading dose then 6mg/kg, then single agent until disease progression Etoposide: etoposide 100 mg/m2 daily for 3 days every three weeks for 6 cycles Trastuzumab: intravenous trastuzumab 8 mg/kg loading dose and then 6 mg/kg every three weeks and then single agent trastuzumab until progression of disease
All Cause Mortality
	Single Arm Study
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Single Arm Study
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Single Arm Study
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

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.