Fulvestrant With or Without AZD6244 in Treating Patients With Advanced Breast Cancer That Progressed After Aromatase Inhibitor Therapy

Phase 2

Completed

• Conditions: Breast Cancer
• Interventions: Drug: fulvestrant; Drug: selumetinib

• Registration Number: NCT01160718
• Lead Sponsor: Swiss Group for Clinical Cancer Research

Brief Summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. AZD6244 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether fulvestrant is more effective with or without AZD6244 in treating patients with advanced breast cancer.

PURPOSE: This randomized phase II trial is studying how well fulvestrant works with or without AZD6244 in treating patients with advanced breast cancer that progressed after aromatase inhibitor therapy.

Detailed Description

OBJECTIVES:

Primary

* To assess the efficacy of fulvestrant with versus without MEK inhibitor AZD6244 in patients with advanced stage, endocrine-sensitive breast cancer that progressed after aromatase inhibitor therapy.

Secondary

* To assess the safety and tolerability of this regimen in these patients.

* To examine other outcome parameters.

* To develop a virtual tissue bank for future translational research.

OUTLINE: This is a multicenter study. Patients are stratified according to center, prior treatment with tamoxifen citrate (yes vs no), the setting in which prior aromatase inhibitor was given (adjuvant treatment vs advanced stage treatment), HER-2 disease (positive vs negative), visceral metastasis (present vs absent), performance status (0 vs 1 or 2), and disease (measurable disease vs bone-only disease or small but unequivocal liver or lung metastases). Patients are randomized to 1 of 2 treatment arms.

* Arm I (experimental): Patients receive fulvestrant intramuscularly (IM) on days 1 and 15 of course 1 and on day 1 of each subsequent course. Patients also receive oral AZD6244 twice daily on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

* Arm II (control): Patients receive fulvestrant as in arm I. Patients also receive oral placebo twice daily on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months thereafter.

Study Timeline

• Study First Submitted: 2010-07-09
• Study First Submitted QC: 2010-07-09
• Study First Posted: 2010-07-12
• Study Start: 2010-08
• Primary Completion: 2012-12
• Study Completion: 2016-09
• Status Verified: 2019-05
• Last Update Submitted: 2019-05-13
• Last Update Posted: 2019-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 46

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: Fulvestrant / AZD6244	fulvestrant	Fulvestrant 500mg i.m. day 1, 15, day 1 of cycle 2, then every 28 +/- 3 days AZD6244 75 mg p.o. bid
Arm A: Fulvestrant / AZD6244	selumetinib	Fulvestrant 500mg i.m. day 1, 15, day 1 of cycle 2, then every 28 +/- 3 days AZD6244 75 mg p.o. bid
Arm B: Fulvestrant / Placebo	fulvestrant	Fulvestrant 500mg i.m. day 1, 15, day 1 of cycle 2, then every 28 +/- 3 days Placebo 3 caps p.o. bid (same appearance as AZD6244)

Primary Outcome Measures

Name	Time	Method
Disease control (sum of complete response, partial response, and stable disease) at 24 weeks or more according to RECIST 1.1 criteria	at 24 weeks or more according to RECIST 1.1 criteria

Secondary Outcome Measures

Name	Time	Method
Duration of response	will be calculated from the time that measurement criteria are met for the first time until documented tumor progression.
Overall survival	Overall survival will be calculated from registration until death
Adverse events	according to NCI CTCAE v 4.0
Overall response	according to RECIST 1.1
Progression-free survival	will be calculated from randomization until documented tumor progression or death, whichever occurs first.
Time to treatment failure	will be calculated from randomization to discontinuation of all trial treatment due to any reason

Trial Locations

Locations (17)

Kantonsspital Aarau; 🇨🇭 Aarau, Switzerland

Kantonsspital Baden; 🇨🇭 Baden, Switzerland

City Hospital Triemli; 🇨🇭 Zurich, Switzerland

Inselspital Bern; 🇨🇭 Bern, Switzerland

Kantonsspital Luzern; 🇨🇭 Luzerne, Switzerland

Spitalzentrum Biel; 🇨🇭 Biel, Switzerland

Universitair Ziekenhuis Gent; 🇧🇪 Ghent, Belgium

Universitaetsspital-Basel; 🇨🇭 Basel, Switzerland

U.Z. Gasthuisberg; 🇧🇪 Leuven, Belgium

Kantonsspital Graubuenden; 🇨🇭 Chur, Switzerland

Hopitaux Universitaires de Geneve; 🇨🇭 Geneva, Switzerland

Kantonsspital Winterthur; 🇨🇭 Winterthur, Switzerland

Kantonsspital - St. Gallen; 🇨🇭 St. Gallen, Switzerland

Oncology Institute of Southern Switzerland - Mendrisio; 🇨🇭 Mendrisio, Switzerland

Hopital de Morges; 🇨🇭 Morges, Switzerland

Brustzentrum Thurgau at Kantonsspital Frauenfeld; 🇨🇭 Frauenfeld, Switzerland

Centre Hospitalier Universitaire Vaudois; 🇨🇭 Lausanne, Switzerland