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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01160718
Recruitment Status : Completed
First Posted : July 12, 2010
Last Update Posted : May 15, 2019
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: fulvestrant Drug: selumetinib Phase 2

Detailed Description:



  • 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.


  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Fulvestrant With or Without AZD6244, a Mitogen-Activated Protein Kinase Kinase (MEK) ½ Inhibitor, in Advanced Stage Breast Cancer Progressing After Aromatase Inhibitor: A Randomized Placebo-Controlled Double-Blind Phase II Trial
Study Start Date : August 2010
Actual Primary Completion Date : December 2012
Actual Study Completion Date : September 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Fulvestrant

Arm Intervention/treatment
Active Comparator: 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
Drug: 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
Other Name: ZD9238

Drug: selumetinib
AZD6244 75 mg p.o. bid
Other Name: AZD6244

Placebo Comparator: 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)
Drug: 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
Other Name: ZD9238

Primary Outcome Measures :
  1. Disease control (sum of complete response, partial response, and stable disease) at 24 weeks or more according to RECIST 1.1 criteria [ Time Frame: at 24 weeks or more according to RECIST 1.1 criteria ]

Secondary Outcome Measures :
  1. Adverse events [ Time Frame: according to NCI CTCAE v 4.0 ]
  2. Overall response [ Time Frame: according to RECIST 1.1 ]
  3. Progression-free survival [ Time Frame: will be calculated from randomization until documented tumor progression or death, whichever occurs first. ]
  4. Time to treatment failure [ Time Frame: will be calculated from randomization to discontinuation of all trial treatment due to any reason ]
  5. Duration of response [ Time Frame: will be calculated from the time that measurement criteria are met for the first time until documented tumor progression. ]
  6. Overall survival [ Time Frame: Overall survival will be calculated from registration until death ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • Histologically or cytologically confirmed breast cancer

    • Not amenable to curative therapy
  • HER-2 positive disease allowed
  • Disease relapse or progression after aromatase inhibitor as adjuvant therapy or for advanced stage disease
  • Bilateral breast cancer allowed provided tumor endocrine sensitivity has been proven on both sides
  • Measurable disease according to RECIST criteria v1.1 or other lesions assessable by radiological exams (i.e., bone-only disease or small but unequivocal liver or lung metastases)
  • Received no more than 1 line of chemotherapy for advanced stage disease
  • Estrogen receptor- and/or progesterone receptor-positive (≥ 10% tumor cells positive by immunohistochemistry or ≥ 10 fmol/mg cytosol protein by ligand binding assay)
  • No known CNS metastases

    • Patients with brain metastases treated with radiotherapy and without any sign of brain progression after ≥ 3 months since the end of radiotherapy may be considered eligible after trial chair approval)


  • 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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01160718

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Universitair Ziekenhuis Gent
Ghent, Belgium, B-9000
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
Kantonsspital Aarau
Aarau, Switzerland, CH-5001
Kantonsspital Baden
Baden, Switzerland, CH-5404
Basel, Switzerland, CH-4031
Inselspital Bern
Bern, Switzerland, CH-3010
Spitalzentrum Biel
Biel, Switzerland, CH-2501
Kantonsspital Graubuenden
Chur, Switzerland, CH-7000
Brustzentrum Thurgau at Kantonsspital Frauenfeld
Frauenfeld, Switzerland, 8501
Hopitaux Universitaires de Geneve
Geneva, Switzerland, CH-1226
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Kantonsspital Luzern
Luzerne, Switzerland, CH-6000
Oncology Institute of Southern Switzerland - Mendrisio
Mendrisio, Switzerland, CH-6850
Hopital de Morges
Morges, Switzerland, CH-1110
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Kantonsspital Winterthur
Winterthur, Switzerland, CH-8400
City Hospital Triemli
Zurich, Switzerland, CH-8063
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
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Study Chair: Khalil Zaman, MD Centre Hospitalier Universitaire Vaudois
Study Chair: Lucien Perey, MD Hopital de Morges
Study Chair: Patrick Neven, MD, PhD University Hospital, Gasthuisberg

Publications of Results:
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Responsible Party: Swiss Group for Clinical Cancer Research Identifier: NCT01160718     History of Changes
Other Study ID Numbers: SAKK 21/08
First Posted: July 12, 2010    Key Record Dates
Last Update Posted: May 15, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Swiss Group for Clinical Cancer Research:
estrogen receptor-positive breast cancer
HER2-positive breast cancer
HER2-negative breast cancer
progesterone receptor-positive breast cancer
recurrent breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Aromatase Inhibitors
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action