Clinical trial NCT01160718 (phase 2, status: completed)
Conditions: breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: fulvestrant, selumetinib
SMILES: [H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])C3=CC=C(O)C=C3C[C@@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)[C@@]21[H], CN1C=NC2=C1C=C(C(O)=NOCCO)C(NC1=C(Cl)C=C(Br)C=C1)=C2F
Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  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)

        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