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

Phase 3

Completed

Conditions: Breast Cancer

Interventions: Drug: Anastrozole
Drug: Exemestane
Drug: Fulvestrant

Registration Number: NCT00253422

Lead Sponsor: Institute of Cancer Research, United Kingdom

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 698

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Faslodex + placebo	Anastrozole	Arimidex/placebo comparator is blinded Faslodex (fulvestrant) IM on day 1,15,29 and monthly thereafter Placebo orally once a day
Faslodex + placebo	Fulvestrant	Arimidex/placebo comparator is blinded Faslodex (fulvestrant) IM on day 1,15,29 and monthly thereafter Placebo orally once a day
Faslodex + Arimidex	Anastrozole	Arimidex/placebo comparator is blinded Faslodex (fulvestrant) IM on day 1,15,29 and monthly thereafter Arimidex (anastrozole) orally once a day
Faslodex + Arimidex	Fulvestrant	Arimidex/placebo comparator is blinded Faslodex (fulvestrant) IM on day 1,15,29 and monthly thereafter Arimidex (anastrozole) orally once a day
Exemestane	Exemestane	exemestane orally once a day

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	Assessed up to 190 months	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.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate	From start of treatment, every 3 months to treatment discontinuation and/or up to 190 months	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
Duration of Response	Assessed up to 190 months	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.
Clinical Benefit Rate	Assessed up to 190 months	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.
Duration of Clinical Benefit	Assessed up to 190 months	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 to Treatment Failure	To discontinuation of protocol treatment for any reason, or progression of disease assessed up to 190 months	Time from randomisation to discontinuation of protocol treatment for any reason, or progression of disease
Overall Survival	To death assessed up to 190 months.	Time from randomisation until death from any cause.
Tolerability of Treatment	From start of treatment to discontinuation of treatment/progression assessed up to 190 months	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.

Trial Locations

Locations (2): Institute Of Cancer Research
🇬🇧
Sutton, England, United Kingdom
Royal Marsden - London
🇬🇧
London, England, United Kingdom
Institute Of Cancer Research
🇬🇧Sutton, England, United Kingdom