Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active Postmenopausal NCI UCLA-0502057-01 TORI-B-04, NCT00138125

Objectives

Primary

1. 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

1. Compare the duration of response in patients treated with these regimens.
2. Compare overall survival of patients treated with these regimens.
3. Compare the antitumor activity of these regimens, in terms of time to disease progression, in these patients.
4. Compare the clinical benefit of these regimens in these patients.
5. Determine the safety and toxicity of these regimens in these patients.
6. Correlate HER2/neu expression and ER and/or PR expression with response in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed adenocarcinoma of the breast at first diagnosis
  • Stage IV disease



• Measurable disease



• HER2/neu-positive disease by fluorescence in situ hybridization
  • Amplification ≥ 2.0



• No prior or current brain metastases



• Hormone receptor status:
  • Estrogen receptor- and/or progesterone receptor-positive tumor by immunohistochemistry
    • At least 10% tumor staining OR Allred score ≥ 3 for positivity

Prior/Concurrent Therapy:

Biologic therapy

• At least 6 months since prior adjuvant trastuzumab (Herceptin®)
• No prior trastuzumab for metastatic breast cancer

Chemotherapy

• Prior adjuvant chemotherapy allowed
• No prior chemotherapy for metastatic breast cancer
• No concurrent chemotherapy

Endocrine therapy

• At least 6 months since prior adjuvant tamoxifen or aromatase inhibitor therapy
• At least 4 weeks since prior endocrine therapy (4 months for luteinizing hormone-releasing hormone analog) and recovered
• No prior fulvestrant
• No prior endocrine therapy for metastatic breast cancer
• No other concurrent endocrine therapy

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery

• At least 4 weeks since prior surgery and recovered

Other

• No prior investigational therapy for metastatic breast cancer
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• No concurrent long-term anticoagulant therapy, except antiplatelet therapy (e.g., warfarin)
  • Concurrent low-dose warfarin allowed provided INR is ≤1.6

Patient Characteristics:

Age

• Postmenopausal

Sex

• Female

Menopausal status

• Postmenopausal, defined by 1 of the following:
  • Prior bilateral oophorectomy
  • 60 years of age or older
  • 45 years of age or older with amenorrhea for ≥ 12 months AND uterus is intact
  • Follicle-stimulating hormone and estradiol levels within postmenopausal range

Performance status

• ECOG 0-2

Life expectancy

• At least 24 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm³
• Hemoglobin ≥ 10 g/dL
• Platelet count ≥ 100,000/mm³
• No history of bleeding diathesis (e.g., disseminated intravascular coagulation or clotting factor deficiency)

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN) (Gilbert's syndrome allowed)
• AST and ALT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 5.0 times ULN, except in the presence of documented bone metastases and the absence of known hepatic disease

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• LVEF ≥ lower limit of normal
• No New York Heart Association class II-IV congestive heart failure
• No uncontrolled hypertension
• No myocardial infarction
• No unstable angina
• No serious cardiac arrhythmia requiring medication
• No other clinically significant cardiovascular disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
• No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No active uncontrolled infection requiring parenteral antimicrobials
• No other medical or psychiatric disorder that would preclude study treatment
• No known hypersensitivity to any of the study drugs or to active or inactive excipients of fulvestrant (e.g., castor oil or mannitol)

Expected Enrollment

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

Outcomes

Overall objective tumor response rate at baseline and after every 3 courses of treatment

Duration of objective response at baseline and after every 3 courses of treatment
Time to tumor progression at baseline and after every 3 courses of treatment
Duration of survival at baseline and after every 3 courses of treatment
Clinical benefit (including complete response, disease progression, or stable disease) at 24, 36, and 48 weeks
Safety and toxicity at baseline and after every 3 courses of treatment
Interrelationships between HER-2 and estrogen receptor (ER) or progesterone receptor (PR) expression with response at baseline and after every 3 courses of treatment

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.

Trial Contact Information

Trial Lead Organizations

Jonsson Comprehensive Cancer Center at UCLA

Richard Pietras, MD, PhD, Protocol chair		Ph: 310-825-9769; 888-798-0719 Email: rpietras@ucla.edu

U.S.A.
California
	Los Angeles
	Jonsson Comprehensive Cancer Center at UCLA
		Clinical Trials Office - Jonsson Comprehensive Cancer Center at UCLA	Ph:  888-798-0719

Registry Information
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
Trial Start Date		2005-05-31
Registered in ClinicalTrials.gov		NCT00138125
Date Submitted to PDQ		2005-06-29
Information Last Verified		2007-04-13
NCI Grant/Contract Number		CA16042