Study of Faslodex +/- Concomitant Arimidex v Exemestane Following Progression on Non-steroidal Aromatase Inhibitors

Institute of Cancer Research, United Kingdom698 enrolled

Overview

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant, anastrozole, or exemestane may fight breast cancer by blocking the use of estrogen by the tumor cells or by lowering the amount of estrogen the body makes. It is not yet known whether giving fulvestrant together with anastrozole is more effective than giving fulvestrant together with a placebo or exemestane alone in treating breast cancer. PURPOSE: This randomized phase III trial is studying fulvestrant and anastrozole to see how well they work compared to fulvestrant and a placebo or exemestane alone in treating postmenopausal women with locally advanced or metastatic breast cancer.

OBJECTIVES: Primary * Compare progression-free survival of postmenopausal women with estrogen receptor- and/or progesterone receptor-positive, locally advanced or metastatic breast cancer that relapsed or progressed during prior treatment with nonsteroidal aromatase inhibitors treated with fulvestrant with vs without anastrozole vs exemestane alone. Secondary * Compare the objective complete response (CR) and partial response (PR) rate and duration of response in patients treated with these regimens. * Compare the clinical benefit (i.e., 6-month CR, PR, and stable disease) rate and duration of clinical benefit in patients treated with these regimens. * Compare time to treatment failure in patients treated with these regimens. * Compare the overall survival of patients treated with these regimens. * Compare the tolerability of these regimens in these patients. OUTLINE: This is a randomized, partially double-blind and placebo-controlled, multicenter study. Patients are stratified according to the setting in which prior nonsteroidal aromatase-inhibitor therapy was given (adjuvant therapy vs first-line therapy) and participating center. Patients are randomized to 1 of 3 treatment arms. * Arm I (fulvestrant and anastrozole): Patients receive fulvestrant intramuscularly (IM) on days 1, 15, and 29 and then once monthly. Patients receive oral anastrozole once daily. * Arm II (fulvestrant and placebo): Patients receive fulvestrant as in arm I and oral placebo once daily. * Arm III (exemestane alone): Patients receive oral exemestane once daily. In all arms, treatment repeats every month in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for survival. PROJECTED ACCRUAL: A total of 750 patients (250 per treatment arm) will be accrued for this study.

Study Type

INTERVENTIONAL

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 120 Years

Medical Language ↔ Plain English

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed adenocarcinoma of the breast * Locally advanced or metastatic disease * Metastatic disease must be measurable or evaluable * Patients with bone only metastases are eligible provided there is an evaluable site of bone metastasis that can be followed by x-ray, MRI, or CT scan * Relapsed or progressed during prior treatment with single-agent nonsteroidal aromatase inhibitor (NSAI)\*, meeting either of the following criteria: * NSAI given as adjuvant therapy that lasted ≥ 12 months * Achieved an objective complete response, partial response, or stable disease that lasted ≥ 6 months after prior first-line therapy with NSAI for locally advanced or metastatic disease * Chemotherapy as part of the first-line therapy given before initiation of NSAI allowed NOTE: \*Patients are required to continue to take NSAI until beginning of study treatment. * No rapidly progressive visceral disease (i.e., lymphangitis carcinomatosa or diffuse hepatic involvement) * Hormone receptor status: * Estrogen receptor (ER) and/or progesterone receptor positive tumor * No ER-unknown disease PATIENT CHARACTERISTICS: Sex * Female Menopausal status * Postmenopausal, as defined by 1 of the following criteria: * Age 60 and over * Age 45 to 59 AND ≥ 12 months since last menstrual period with no prior hysterectomy * Any age with prior bilateral oophorectomy Performance status * WHO 0-2 Life expectancy * More than 3 months Hematopoietic * Neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * No thrombocytopenia * Hemoglobin ≥ 10 g/dL Hepatic * AST and ALT ≤ 2.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 5 times ULN (unless due to bone metastases) * No liver disease Renal * Creatinine \< 1.97 mg/dL Other * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Chemotherapy * See Disease Characteristics * Prior neoadjuvant or adjuvant chemotherapy allowed Endocrine therapy * See Disease Characteristics * Prior tamoxifen as neoadjuvant or adjuvant therapy allowed * No systemic corticosteroids that lasted \> 15 days within the past 4 weeks Other * More than 4 weeks since prior investigational drugs * Concurrent bisphosphonates for bone metastases allowed provided bisphosphonate therapy has been established for ≥ 6 months * Concurrent initiation of bisphosphonate allowed provided patient has soft tissue or visceral metastases as the measurable or evaluable target lesion * No concurrent anticoagulant therapy * No concurrent unlicensed noncancer investigational agents

Outcomes

Primary Outcomes

Progression-free Survival

defined as time from randomisation to progression of existing disease, new sites of disease, second primary cancer if change in systemic treatment was necessary, or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Time frame: Assessed up to 190 months

Secondary Outcomes

Objective Response Rate

The proportion of patients identified as having a complete response (CR) or partial response (PR) at any time whilst on study treatment. Response is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as either disappearance of all lesions or a \>=30% decrease in the sum of the longest diameter of target lesions with no progressing non-target lesions and no new lesions. Objective Response (OR) = CR + PR

Time frame: From start of treatment, every 3 months to treatment discontinuation and/or up to 190 months

Duration of Response

time from first assessment of response to progression or death. Response is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as either disappearance of all lesions or a \>=30% decrease in the sum of the longest diameter of target lesions with no progressing non-target lesions and no new lesions. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Time frame: Assessed up to 190 months

Clinical Benefit Rate

Complete or partial response or stable disease for at least six months prior to progression. Response is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as either disappearance of all lesions or a \>=30% decrease in the sum of the longest diameter of target lesions with no progressing non-target lesions and no new lesions. Stable disease is neither responding or progressing. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Time frame: Assessed up to 190 months

Duration of Clinical Benefit

Time from first assessment of clinical benefit to progression or death. Response is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as either disappearance of all lesions or a \>=30% decrease in the sum of the longest diameter of target lesions with no progressing non-target lesions and no new lesions. Stable disease is neither responding or progressing. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Clinical benefit = (CR+PR)+(SD\>=6months).

Time frame: Assessed up to 190 months

Time to Treatment Failure

Time from randomisation to discontinuation of protocol treatment for any reason, or progression of disease

Time frame: To discontinuation of protocol treatment for any reason, or progression of disease assessed up to 190 months

Overall Survival

Time from randomisation until death from any cause.

Time frame: To death assessed up to 190 months.

Tolerability of Treatment

To evaluate the overall safety and tolerability. The number of patients experiencing at least one adverse event. Refer to adverse event section for more details.

Time frame: From start of treatment to discontinuation of treatment/progression assessed up to 190 months

Study of Faslodex +/- Concomitant Arimidex v Exemestane Following Progression on Non-steroidal Aromatase Inhibitors

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes