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

NCT ID: NCT01160718

Last Updated: 2019-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2016-09-30

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm A: Fulvestrant / AZD6244

Fulvestrant 500mg i.m. day 1, 15, day 1 of cycle 2, then every 28 +/- 3 days AZD6244 75 mg p.o. bid

Group Type: ACTIVE_COMPARATOR

fulvestrant

Intervention Type: DRUG

Arm A: Fulvestrant 500mg i.m. day 1, 15, day 1 of cycle 2, then every 28 +/- 3 days Arm B: Fulvestrant 500mg i.m. day 1, 15, day 1 of cycle 2, then every 28 +/- 3 days

selumetinib

Intervention Type: DRUG

AZD6244 75 mg p.o. bid

Arm B: Fulvestrant / Placebo

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)

Group Type: PLACEBO_COMPARATOR

fulvestrant

Intervention Type: DRUG

Arm A: Fulvestrant 500mg i.m. day 1, 15, day 1 of cycle 2, then every 28 +/- 3 days Arm B: Fulvestrant 500mg i.m. day 1, 15, day 1 of cycle 2, then every 28 +/- 3 days

Interventions

fulvestrant

Arm A: Fulvestrant 500mg i.m. day 1, 15, day 1 of cycle 2, then every 28 +/- 3 days Arm B: Fulvestrant 500mg i.m. day 1, 15, day 1 of cycle 2, then every 28 +/- 3 days

Intervention Type: DRUG

selumetinib

AZD6244 75 mg p.o. bid

Intervention Type: DRUG

Other Intervention Names

ZD9238; AZD6244

Eligibility Criteria

Inclusion Criteria

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Postmenopausal
• Hemoglobin ≥ 90 g/L
• Platelet count ≥ 100 x 10^9/L
• Absolute neutrophil count ≥ 1.5 x 10^9/L
• Creatinine clearance ≥ 30 mL/min
• ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN in patients with liver metastases)
• Bilirubin ≤ 1.5 times ULN
• INR < 1.6
• PTT normal
• LVEF ≥ 50%
• Able to swallow AZD6244/placebo capsules
• Capable of understanding information given by the investigator on the trial
• Must adhere to and be geographically proximal to allow for proper staging, treatment, and follow up
• No contraindication for intramuscular injections
• No bleeding diathesis
• No current or prior malignancy other than breast cancer within the past 5 years, except carcinoma in situ of the cervix or basal cell carcinoma of the skin treated curatively
• No serious underlying medical condition that, in the judgment of the investigator, would impair the ability of the patient to participate in the trial (e.g., active autoimmune disease or uncontrolled diabetes)
• No refractory nausea and vomiting, chronic gastrointestinal disease (e.g., inflammatory bowel disease), or significant bowel resection that preclude adequate absorption
• No psychiatric disorder precluding understanding of information on trial-related topics, giving informed consent, or interfering with adherence for oral drug intake
• No uncontrolled hypertension (systolic BP > 150 mm Hg and/or diastolic BP > 100 mm Hg, measured repeatedly at more than two visits despite adequate treatment with at least two different antihypertensive drugs)
• No clinically significant (i.e., active) cardiovascular disease, including any of the following:

• Cerebrovascular accident/stroke or myocardial infarction within the past 6 months
• Unstable angina
• NYHA class III-IV congestive heart failure
• Serious cardiac arrhythmia or AV-block > 1, requiring medication during the trial and which might interfere with regularity of the trial treatment, or not controlled by medication
• No known hypersensitivity to trial drugs or any other component of the trial drugs

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 30 days since other prior experimental drugs or participation in another clinical trial
• No prior fulvestrant, AZD6244, MEK inhibitors, RAF inhibitors, or endocrine therapies other than aromatase inhibitors (e.g., anastrazole, letrozole, or exemestane) or tamoxifen
• No more than 1 line of aromatase inhibitors (steroidal and nonsteroidal aromatase inhibitors are considered two different lines)
• No concurrent full-dose anticoagulation therapy (e.g., low molecular weight heparin, acenocoumarol, phenprocoumon, or analogues)

• Prophylactic doses of anticoagulation or antiplatelet may be allowed
• No concurrent radiotherapy
• No other concurrent anticancer therapy or experimental drugs
• Concurrent bisphosphonate allowed provided the investigator rules out tumor progression

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Khalil Zaman, MD

Role: STUDY_CHAIR

Centre Hospitalier Universitaire Vaudois

Lucien Perey, MD

Role: STUDY_CHAIR

Hopital de Morges

Patrick Neven, MD, PhD

Role: STUDY_CHAIR

University Hospital, Gasthuisberg

Locations

Universitair Ziekenhuis Gent

Ghent, , Belgium

U.Z. Gasthuisberg

Leuven, , Belgium

Kantonsspital Aarau

Aarau, , Switzerland

Kantonsspital Baden

Baden, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Inselspital Bern

Bern, , Switzerland

Spitalzentrum Biel

Biel, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

Brustzentrum Thurgau at Kantonsspital Frauenfeld

Frauenfeld, , Switzerland

Hopitaux Universitaires de Geneve

Geneva, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital Luzern

Luzerne, , Switzerland

Oncology Institute of Southern Switzerland - Mendrisio

Mendrisio, , Switzerland

Hopital de Morges

Morges, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

City Hospital Triemli

Zurich, , Switzerland

Countries

Belgium; Switzerland

References

Zaman K, Winterhalder R, Mamot C, Hasler-Strub U, Rochlitz C, Mueller A, Berset C, Wiliders H, Perey L, Rudolf CB, Hawle H, Rondeau S, Neven P. Fulvestrant with or without selumetinib, a MEK 1/2 inhibitor, in breast cancer progressing after aromatase inhibitor therapy: a multicentre randomised placebo-controlled double-blind phase II trial, SAKK 21/08. Eur J Cancer. 2015 Jul;51(10):1212-20. doi: 10.1016/j.ejca.2015.03.016. Epub 2015 Apr 16.

Reference Type: RESULT

PMID: 25892646 (View on PubMed)

Other Identifiers

SWS-SAKK-21/08

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2010-019965-27

Identifier Type: -

Identifier Source: secondary_id

EU-21046

Identifier Type: -

Identifier Source: secondary_id

CDR0000680800

Identifier Type: -

Identifier Source: secondary_id

SAKK 21/08

Identifier Type: -

Identifier Source: org_study_id