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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT01160718
First received: July 9, 2010
Last updated: December 8, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Breast Cancer
Drug: fulvestrant
Drug: selumetinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse events [ Time Frame: according to NCI CTCAE v 4.0 ] [ Designated as safety issue: Yes ]
  • Overall response [ Time Frame: according to RECIST 1.1 ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: will be calculated from randomization until documented tumor progression or death, whichever occurs first. ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: will be calculated from randomization to discontinuation of all trial treatment due to any reason ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: will be calculated from the time that measurement criteria are met for the first time until documented tumor progression. ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Overall survival will be calculated from registration until death ] [ Designated as safety issue: No ]

Estimated Enrollment: 89
Study Start Date: August 2010
Estimated Study Completion Date: December 2015
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01160718

Locations
Belgium
Universitair Ziekenhuis Gent
Ghent, Belgium, B-9000
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
Switzerland
Kantonsspital Aarau
Aarau, Switzerland, CH-5001
Kantonsspital Baden
Baden, Switzerland, CH-5404
Universitaetsspital-Basel
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
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
Hopitaux Universitaires de Geneve
Thonex-Geneve, Switzerland, CH-1226
Kantonsspital Winterthur
Winterthur, Switzerland, CH-8400
City Hospital Triemli
Zurich, Switzerland, CH-8063
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Khalil Zaman, MD Centre Hospitalier Universitaire Vaudois
Study Chair: Lucien Perey, MD Hopital de Morges
Study Chair: Patrick Neven, MD, PhD U.Z. Gasthuisberg
  More Information

No publications provided

Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT01160718     History of Changes
Other Study ID Numbers: SAKK 21/08, SWS-SAKK-21/08, EUDRACT-2010-019965-27, EU-21046, CDR0000680800
Study First Received: July 9, 2010
Last Updated: December 8, 2013
Health Authority: Switzerland: Swissmedic

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:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Estradiol
Aromatase Inhibitors
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Estrogens
Hormones
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 29, 2014