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

Alternate Title

Anastrozole With or Without Trastuzumab in Treating Postmenopausal Women With Metastatic Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III, Phase II	Treatment	Closed	18 and over	Pharmaceutical / Industry	ROCHE-BO16216 CWRU-030118, GENENTECH-H2223g, ROCHE-1100, ROCHE-B016216F, NCT00022672

Objectives

1. Compare the efficacy of anastrozole with or without trastuzumab (Herceptin), in terms of progression-free survival, in postmenopausal women with hormone-receptor positive HER2-overexpressing metastatic breast cancer.
2. Compare the safety profile of these regimens in these patients.
3. Compare the overall clinical-benefit rate in patients treated with these regimens.
4. Compare the overall survival, duration of response, and 2-year survival of patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed metastatic breast cancer
  • HER2 overexpression (3+) by immunohistochemistry

    OR

  • Any degree of erbB-2 amplification (at least 2 fold) by FISH



• Measurable or evaluable disease



• Postmenopausal as defined by any of the following:
  • At least 60 years of age
  • Under 60 years of age and amenorrheic for at least 12 months
  • Under 60 years of age, without a uterus, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) values within postmenopausal range
  • Menopausal age (under 60), amenorrheic for 12 months or less, and LH and FSH values within postmenopausal range
  • Prior bilateral oophorectomy
  • Prior radiation castration with amenorrhea for at least 6 months



• No clinical or radiological evidence of CNS metastases



• Hormone receptor status:
  • Estrogen-receptor positive

    AND/OR

  • Progesterone-receptor positive

Prior/Concurrent Therapy:

Biologic therapy:

• No prior anti-HER2 therapy
• No other concurrent anticancer immunotherapy

Chemotherapy:

• At least 6 months since prior adjuvant chemotherapy
• No prior chemotherapy for metastatic disease
• No concurrent anticancer chemotherapy

Endocrine therapy:

• Prior first-line tamoxifen for metastatic disease allowed if partial or complete response or stable disease for more than 6 months
• At least 1 day since prior tamoxifen
• No more than 4 weeks (duration) of prior anastrozole
• No concurrent steroid treatment for cancer
• No concurrent hormone replacement therapy
• No other concurrent anticancer hormonal therapy

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy to indicator lesion, unless objective disease recurrence or progression within radiation portal since completion of radiotherapy
• No concurrent radiotherapy to only known site of disease
• Concurrent palliative radiotherapy allowed

Surgery:

• See Disease Characteristics
• No concurrent resection of only known site of disease
• Concurrent palliative surgery allowed

Other:

• At least 30 days since prior investigational drugs
• Prior or concurrent bisphosphonate therapy allowed
• No other concurrent specific anticancer therapy

Patient Characteristics:

Age:

• See Disease Characteristics
• 18 and over

Sex:

• Female

Menopausal status:

• See Disease Characteristics

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 3,000/mm³
• Neutrophil count greater than 1,500/mm³
• Platelet count greater than 100,000/mm³
• Hemoglobin greater than 9 g/dL

Hepatic:

• Transaminases less than 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases present)

Renal:

• Creatinine less than 1.5 times ULN

Cardiovascular:

• LVEF greater than 50% by echocardiogram or MUGA
• No uncontrolled cardiac disease (e.g., angina, arrhythmias, or hypertension)
• No prior congestive heart failure
• No myocardial infarction within the past 6 months

Pulmonary:

• No severe dyspnea at rest due to complications of advanced malignancy
• No requirement for supplementary oxygen

Other:

• No concurrent uncontrolled serious illness
• No other prior malignancy that would preclude study compliance
  • Patients with prior nonmelanoma skin cancer, carcinoma in situ of the cervix, or other curatively treated malignancy allowed if disease free for more than 5 years
• No clinical disease that requires immediate cytotoxic chemotherapy
• No known allergy to Chinese hamster ovary cell proteins, murine proteins, or to any excipients of trastuzumab (Herceptin) formulation (e.g., l-histidine, trehalose dihydrate, or polysorbate 20) or preparation (e.g., benzyl alcohol)
• Not pregnant or nursing
• Negative pregnancy test

Expected Enrollment

A total of 202 patients (101 per treatment arm) will be accrued for this study within 2 years.

Outcomes

Progression-free survival

Overall survival
Clinical benefit rate as measured by stable disease or partial or complete response
Time to progression
Two year survival
Duration of response

Outline

This is a randomized, open-label, multicenter study. Patients are stratified according to presence of liver metastases (yes vs no), tumor assessment (measurable disease vs evaluable disease), relapse after prior adjuvant tamoxifen therapy (no prior adjuvant tamoxifen therapy vs relapse at least 12 months after therapy vs relapse during or fewer than 12 months after therapy), and concurrent bisphosphonate therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral anastrozole once daily and trastuzumab (Herceptin) IV over 30-90 minutes once weekly.



• Arm II: Patients receive anastrozole as in arm I.

In both arms, treatment continues for at least 2 years in the absence of disease progression or unacceptable toxicity. Patients in either arm who do not develop disease progression may continue receiving treatment, in the arm to which they were originally randomized, during the extension phase of this study. Patients in arm II who develop disease progression may receive treatment in arm I during the extension phase in the absence of further disease progression.

Patients are followed at 28 days.

Trial Contact Information

Trial Lead Organizations

Hoffmann-La Roche, Incorporated

Michaela Lehle, PhD, Protocol chair		Ph: 41-61-688-0638 Email: michaela.lehle@roche.com

Registry Information
Official Title		A Randomized, Controlled, Open-Label Study To Evaluate The Efficacy And Safety Of Herceptin (TRASTUZUMAB) In Combination With The Oral Aromatase Inhibitor ARIMIDEX (ANASTROZOLE) Compared With ARIMIDEX Alone As First And Second Line Treatment Administered To Postmenopausal, Hormone Receptor-Positive (ER+VE And/Or PR+VE) Patients With HER2 Overexpressing Metastatic Breast Cancer
Trial Start Date		2000-11-17
Registered in ClinicalTrials.gov		NCT00022672
Date Submitted to PDQ		2001-06-28
Information Last Verified		2006-04-17

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