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

NCT01160718 | Completed Phase 2

• 5 other identifiers: SAKK 21/08SWS-SAKK-21/08EUDRACT-2010-019965-27EU-21046CDR0000680800
• Study Type: interventional
• Target: 46
• Locations: 2 countries
• Sites: 17

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.

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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

• Duration of response

  will be calculated from the time that measurement criteria are met for the first time until documented tumor progression.

Study Arms (2)

Arm A: Fulvestrant / AZD6244

ACTIVE COMPARATOR

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; Drug: selumetinib

Arm B: Fulvestrant / Placebo

PLACEBO COMPARATOR

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

Interventions

fulvestrant 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

Also known as: ZD9238

Arm A: Fulvestrant / AZD6244; Arm B: Fulvestrant / Placebo

selumetinib DRUG

AZD6244 75 mg p.o. bid

Also known as: AZD6244

Arm A: Fulvestrant / AZD6244

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (17)

Universitair Ziekenhuis Gent

Ghent, B-9000, Belgium

Location

U.Z. Gasthuisberg

Leuven, B-3000, Belgium

Location

Kantonsspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, CH-5404, Switzerland

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Spitalzentrum Biel

Biel, CH-2501, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Brustzentrum Thurgau at Kantonsspital Frauenfeld

Frauenfeld, 8501, Switzerland

Location

Hopitaux Universitaires de Geneve

Geneva, CH-1226, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonsspital Luzern

Luzerne, CH-6000, Switzerland

Location

Oncology Institute of Southern Switzerland - Mendrisio

Mendrisio, CH-6850, Switzerland

Location

Hopital de Morges

Morges, CH-1110, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Kantonsspital Winterthur

Winterthur, CH-8400, Switzerland

Location

City Hospital Triemli

Zurich, CH-8063, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 25892646 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant; AZD 6244

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Khalil Zaman, MD

  Centre Hospitalier Universitaire Vaudois

  STUDY CHAIR

• Lucien Perey, MD

  Hopital de Morges

  STUDY CHAIR

• Patrick Neven, MD, PhD

  University Hospital, Gasthuisberg

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2010
• First Posted: July 12, 2010
• Study Start: August 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: September 1, 2016
• Last Updated: May 15, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); CH (15)