Fulvestrant and/or Trastuzumab as First-Line Therapy in Treating Postmenopausal Women With Stage IV Breast Cancer

• Sponsor: Translational Oncology Research International (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00138125
• Collaborator: University of California, Los Angeles (Other), Genentech, Inc. (Industry), AstraZeneca (Industry)
• Enrollment: 2
• Locations: 3
• Arm: 1
• Duration (Months): 56
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by lowering the amount of estrogen the body makes. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving fulvestrant together with trastuzumab is more effective than giving fulvestrant or trastuzumab alone in treating breast cancer.

PURPOSE: This randomized phase II trial is studying how well fulvestrant and/or trastuzumab works as first-line therapy in treating postmenopausal women with stage IV breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Faslodex; Biological: Herceptin	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Compare the overall objective response rate in postmenopausal women with estrogen receptor (ER)- and/or progesterone receptor (PR)-positive, HER2/neu-overexpressing stage IV breast cancer treated with first-line therapy comprising fulvestrant and/or trastuzumab (Herceptin®).

Secondary

• Compare the duration of response in patients treated with these regimens.

• Compare overall survival of patients treated with these regimens.

• Compare the antitumor activity of these regimens, in terms of time to disease progression, in these patients.

• Compare the clinical benefit of these regimens in these patients.

• Determine the safety and toxicity of these regimens in these patients.

• Correlate HER2/neu expression and ER and/or PR expression with response in patients treated with these regimens.

OUTLINE: This is a randomized, controlled, open-label, multicenter study. Patients are stratified according to prior adjuvant endocrine therapy (yes vs no). Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive fulvestrant intramuscularly on days 1 and 15 of course 1 and then on day 1 only in all subsequent courses.

• Arm II: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on days 1, 8, 15, and 22.

• Arm III: Patients receive fulvestrant as in arm I in combination with trastuzumab as in arm II.

In all arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 8 weeks.

PROJECTED ACCRUAL: A total of 120 patients (40 per treatment arm) will be accrued for this study.

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 Randomized Trial of Faslodex and Herceptin, Alone and Combined, in the First - Line Treatment of Hormone Receptor-Positive, HER-2/Neu-Overexpressing Metastatic Breast Cancer
• Study Start Date: Apr 1, 2005
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I see intervention description for details	Drug: Faslodex; Administered IM at 500 mg on day 1 of cycle 1, followed by 500 mg on day 15 of cycle 1, then 500 mg on day 1 of each cycle thereafter.; Biological: Herceptin; Given at 4 mg/kg IV on day 1 (cycle 1) then 2mg/kg IV weekly

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [5 years]

   Of the two treated patients on this trial, the records show that one patient who received Herceptin only completed 3 cycles of therapy, while the second patient who received Herceptin in combination with Faslodex completed 9 cycles of therapy. The last survival data collected from October to November 2008 showed that these two participants were alive at that time.

Secondary Outcome Measures

1. Overall Objective Response Rate [5 years]

   Two patients were treated on a truncated trial. Not enough data was generated for any analysis.

2. Time to Tumor Progression [5 years]

   Two patients were treated on a truncated trial. Not enough data was generated for any analysis.

3. Duration of Response [5 years]

   Two patients were treated on a truncated trial. Not enough data was generated for any analysis.

4. Overall Survival [5 years]

   Two patients were treated on a truncated trial. Not enough data was generated for any analysis.

5. Clinical Benefit (CR + PR + SD > 6 Months) [5 years]

   Two patients were treated on a truncated trial. Not enough data was generated for any analysis.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Female patient, postmenopausal, defined as a woman fulfilling any one of the following criteria:

• Age 60 years or older

• Age 45 years or older with amenorrhea for > 12 months with an intact uterus

• Follicle-stimulating hormone and estradiol levels within post-menopausal range

• Having undergone a bilateral oophorectomy

• Histologically or cytologically proven adenocarcinoma of the breast

• Subjects must have archived rumor tissue available to compare the clinical response with tumor expression of biomarkers, such as HER-2, ER and PR; archived tissue will be used to confirm HER-2, ER and PR status, but results will not be used to determine subject eligibility for the study

• HER2-positive disease

• ER-positive and/or PR-positive disease

• ECOG performance status 0-2

• Life expectancy > 24 weeks

• Left ventricular ejection fraction > lower limit of normal

• No prior chemotherapy, endocrine therapy, Herceptin, or other biologic or investigational therapy for metastatic breast cancer

• No more than two prior endocrine agents in the adjuvant setting as single- or sequential-therapy is permitted, but no prior Faslodex therapy is permitted. A 1-month treatment-free period is required prior to receiving the first dose of trial treatments

• Prior adjuvant chemotherapy is permitted

• Prior adjuvant Herceptin permitted

• At least 1 month since prior surgery, radiotherapy, or endocrine therapy, with complete recovery from the effects of these interventions

• Patients must have ended any hormone replacement therapy at least 1 month prior to receiving the first dose of trial therapy

• Patients treated with bisphosphonates may enroll, with heir bone lesions only assessable for disease progression

• Patient is accessible and willing to comply with treatment and follow-up

• Patient is willing to provide written informed consent prior to the performance of any study-related procedures

• Required laboratory values:

• Absolute neutrophil count > 1.5 x 10^9/L

• Hemoglobin > 10g/dL

• Platelet count > 100 x 10^9/L

• Creatinine < 2.0 mg/dL

• Total bilirubin < 1.5 x upper limit of normal

• AST and ALT < 2.5 x ULN

Exclusion Criteria:

• Prior chemotherapy, hormonal therapy, Herceptin or other investigational therapy for metastatic breast cancer

• Prior treatment with Faslodex

• Concurrent therapy with any other non-protocol anti-cancer therapy

• Current or prior history of brain metastases

• History of any other malignancy within the past 5 years, with the exception of non-melanoma skin cancer or carcinoma-in-situ of the cervix

• Clinically significant cardiovascular disease, New York Heart Association Class II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication

• Prior exposure of > 360 mg/m2 doxorubicin or liposomal doxorubicin, > 120 mg/m2 mitoxantrone, > 90 mg/m2 idarubicin, or > 720 mg/m2 epirubicin

• Active, uncontrolled infection requiring parenteral antimicrobials

• The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of the drugs in this protocol or place the subject at undue risk for treatment complications

• Inability to comply with the study protocol or follow-up procedures

• Known hypersensitivity to any of the drugs used in this protocol or to active or inactive excipients of Faslodex

• History of bleeding diasthesis

• Long-term anticoagulant therapy other than anti-platelet therapy, such as with warfarin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781
2	Cancer Care Associates Medical Group, Inc	Redondo Beach	California	United States	90277
3		San Antonio	Texas	United States

Sponsors and Collaborators

• Translational Oncology Research International
• University of California, Los Angeles
• Genentech, Inc.
• AstraZeneca

Investigators

• Principal Investigator: Richard J. Pietras, MD, PhD, Jonsson Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Translational Oncology Research International
• ClinicalTrials.gov Identifier: NCT00138125
• Other Study ID Numbers: CDR0000439421; UCLA-0502057-01; TORI-B-04; 441350-RI-78322; NCT00203437
• First Posted: Aug 30, 2005
• Last Update Posted: Oct 19, 2020
• Last Verified: Jan 1, 2013

• Keywords provided by Translational Oncology Research International: stage IV breast cancer; recurrent breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Trastuzumab; Fulvestrant

Study Results

Participant Flow

Recruitment Details	recruitment period from June 2005 - August 2008 at academic medical clinics and community medical clinics.

Arm/Group Title	Faslodex + Herceptin
Arm/Group Description	Faslodex : Administered IM at 500 mg on day 1 of cycle 1, followed by 500 mg on day 15 of cycle 1, then 500 mg on day 1 of each cycle thereafter. Herceptin : Given at 4 mg/kg IV on day 1 (cycle 1) then 2mg/kg IV weekly
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Faslodex + Herceptin
Arm/Group Description	Faslodex : Administered IM at 500 mg on day 1 of cycle 1, followed by 500 mg on day 15 of cycle 1, then 500 mg on day 1 of each cycle thereafter. Herceptin : Given at 4 mg/kg IV on day 1 (cycle 1) then 2mg/kg IV weekly
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	2 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 100%
Not Hispanic or Latino	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Of the two treated patients on this trial, the records show that one patient who received Herceptin only completed 3 cycles of therapy, while the second patient who received Herceptin in combination with Faslodex completed 9 cycles of therapy. The last survival data collected from October to November 2008 showed that these two participants were alive at that time.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Faslodex + Herceptin
Arm/Group Description	Faslodex : Administered IM at 500 mg on day 1 of cycle 1, followed by 500 mg on day 15 of cycle 1, then 500 mg on day 1 of each cycle thereafter. Herceptin : Given at 4 mg/kg IV on day 1 (cycle 1) then 2mg/kg IV weekly
Measure Participants	2
Number [participants]	2 100%

2. Secondary Outcome

Title	Overall Objective Response Rate
Description	Two patients were treated on a truncated trial. Not enough data was generated for any analysis.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Two patients were treated on a truncated trial. Not enough data was generated for any analysis.

Arm/Group Title	Arm I
Arm/Group Description	see intervention description for details Faslodex: Administered IM at 500 mg on day 1 of cycle 1, followed by 500 mg on day 15 of cycle 1, then 500 mg on day 1 of each cycle thereafter. Herceptin: Given at 4 mg/kg IV on day 1 (cycle 1) then 2mg/kg IV weekly
Measure Participants	0

3. Secondary Outcome

Title	Time to Tumor Progression
Description	Two patients were treated on a truncated trial. Not enough data was generated for any analysis.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Two patients were treated on a truncated trial. Not enough data was generated for any analysis.

Arm/Group Title	Faslodex + Herceptin
Arm/Group Description	Faslodex : Administered IM at 500 mg on day 1 of cycle 1, followed by 500 mg on day 15 of cycle 1, then 500 mg on day 1 of each cycle thereafter. Herceptin : Given at 4 mg/kg IV on day 1 (cycle 1) then 2mg/kg IV weekly
Measure Participants	0

4. Secondary Outcome

Title	Duration of Response
Description	Two patients were treated on a truncated trial. Not enough data was generated for any analysis.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Two patients were treated on a truncated trial. Not enough data was generated for any analysis.

Arm/Group Title	Arm I
Arm/Group Description	see intervention description for details Faslodex: Administered IM at 500 mg on day 1 of cycle 1, followed by 500 mg on day 15 of cycle 1, then 500 mg on day 1 of each cycle thereafter. Herceptin: Given at 4 mg/kg IV on day 1 (cycle 1) then 2mg/kg IV weekly
Measure Participants	0

5. Secondary Outcome

Title	Overall Survival
Description	Two patients were treated on a truncated trial. Not enough data was generated for any analysis.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Two patients were treated on a truncated trial. Not enough data was generated for any analysis.

Arm/Group Title	Faslodex + Herceptin
Arm/Group Description	Faslodex : Administered IM at 500 mg on day 1 of cycle 1, followed by 500 mg on day 15 of cycle 1, then 500 mg on day 1 of each cycle thereafter. Herceptin : Given at 4 mg/kg IV on day 1 (cycle 1) then 2mg/kg IV weekly
Measure Participants	0

6. Secondary Outcome

Title	Clinical Benefit (CR + PR + SD > 6 Months)
Description	Two patients were treated on a truncated trial. Not enough data was generated for any analysis.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Two patients were treated on a truncated trial. Not enough data was generated for any analysis.

Arm/Group Title	Faslodex + Herceptin
Arm/Group Description	Faslodex : Administered IM at 500 mg on day 1 of cycle 1, followed by 500 mg on day 15 of cycle 1, then 500 mg on day 1 of each cycle thereafter. Herceptin : Given at 4 mg/kg IV on day 1 (cycle 1) then 2mg/kg IV weekly
Measure Participants	0

Adverse Events

Time Frame	Adverse events reported between June 2005 and August 2008.
Arm/Group Title	Faslodex + Herceptin
Arm/Group Description	Faslodex : Administered IM at 500 mg on day 1 of cycle 1, followed by 500 mg on day 15 of cycle 1, then 500 mg on day 1 of each cycle thereafter. Herceptin : Given at 4 mg/kg IV on day 1 (cycle 1) then 2mg/kg IV weekly
All Cause Mortality
	Faslodex + Herceptin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Faslodex + Herceptin
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Faslodex + Herceptin
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Blood and lymphatic system disorders
Leukopenia	2/2 (100%)	2
General disorders
Fever	2/2 (100%)	2

Limitations/Caveats

Trial terminated due to slow patient accrual.Study closed with two subjects enrolled to treatment phase.Slow accrual was due to specific requirements of study population limiting enrollment and possibly due to availability of study drugs in clinic.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.