A Randomized Study of AZD2014 in Combination With Fulvestrant in Metastatic or Advanced Breast Cancer
NCT ID: NCT02216786
Last Updated: 2024-12-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
333 participants
INTERVENTIONAL
2014-01-16
2021-12-31
Brief Summary
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* Fulvestrant
* Fulvestrant + AZD2014 (continuous daily schedule)
* Fulvestrant + AZD2014 (intermittent schedule - 2 days on, 5 days off)
* Fulvestrant + everolimus
Randomization will be stratified by the following criteria:
* Measurable disease (vs. non-measurable).
* Sensitivity to prior endocrine therapy (sensitive versus resistant)
Detailed Description
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* Fulvestrant
* Fulvestrant + AZD2014 (continuous daily schedule)
* Fulvestrant + AZD2014 (intermittent schedule - 2 days on, 5 days off)
* Fulvestrant + everolimus
Randomization will be stratified by the following criteria:
* Measurable disease (vs. non-measurable).
* Sensitivity to prior endocrine therapy (sensitive versus resistant) Sensitivity to prior endocrine therapy is defined as (i) at least 24 months of endocrine therapy before recurrence in the adjuvant setting or (ii) a complete or partial response to prior metastatic endocrine treatment, or (iii) stabilization for at least 24 weeks of endocrine therapy for advanced disease.
Treatment will be continued until disease progression unless there is evidence of unacceptable toxicity or if the patient requests to be withdrawn from the study. If one of the treatments (fulvestrant or mTOR inhibitor) is discontinued prior to disease progression, patients should be continued on single agent treatment until progression, evidence of unacceptable toxicity or if the patient requests to be withdrawn from the study.
At the time of documented disease progression (using RECIST 1.1), patients randomised to receive fulvestrant + everolimus who still meet eligibility criteria may be permitted to receive open-label crossover treatment with fulvestrant + AZD2014. Crossover therapy must begin no later than 28 days after the clinic visit at which progression was determined. Patients will receive crossover therapy until progression, intolerable toxicity, elective withdrawal from the study, or until the completion or termination of the study, whichever occurs first.
Tumour evaluations will be performed before the initiation of treatment, every 8 weeks during the first 40 weeks and every 12 weeks thereafter until disease progression.
The study will also assess the relationship between the anticipated anti-tumour activity of the treatment regimen and biological characteristics of patients' tumour at baseline
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Fulvestrant and AZD2014 (continuous)
Experimental arm
AZD2014
Oral tablet
Fulvestrant
Im injection
Everolimus and Fulvestrant
Comparator arm
Everolimus
Oral tablet
Fulvestrant
Im injection
Fulvestrant
Control 1
Fulvestrant
Im injection
Fulvestrant +AZD2014 (intermittent)
Experimental arm
AZD2014
Oral tablet
Fulvestrant
Im injection
Interventions
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AZD2014
Oral tablet
Everolimus
Oral tablet
Fulvestrant
Im injection
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Women, age ≥18 years
3. Histologically confirmed breast cancer
4. Metastatic or locally recurrent disease; locally recurrent disease must not be amenable to resection with curative intent (patients who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible).
5. Patients must have:
1. at least one lesion, not previously irradiated, that can be measured accurately at baseline as ≥ 10mm in the longest diameter (except lymph nodes which must have short axis ≥ 15mm) with computed tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements, or
2. lytic or mixed (lytic + sclerotic) bone lesions in the absence of measurable disease as defined above; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible
6. Radiological or clinical evidence of recurrence or progression
7. ER-positive disease
8. HER2-negative disease with 0, 1+ or 2+ intensity on IHC and no evidence of amplification on ISH.
9. Formalin fixed, paraffin embedded tumour sample from the primary and/or recurrent cancer must be available for central testing
10. Postmenopausal women.
11. Disease refractory to aromatase inhibitors (AI)
12. Haematologic and biochemical indices within acceptable limits
13. ECOG performance status 0-2
14. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had a hysterectomy, bilateral oophorectomy, bilateral tubular ligation or is post-menopausal (total cessation of menses for ≥ 1 year
Exclusion Criteria
2. More than one line of prior chemotherapy for metastatic breast cancer
3. Prior chemotherapy, biological therapy, androgens, thalidomide, immunotherapy, other anticancer agents or any investigational agents within 14 days of starting study treatment (not including palliative radiotherapy at focal sites), radiotherapy with a wide field of radiation (greater than or equal to 30% marrow or whole pelvis or spine) within 4 weeks of starting study treatment, or strontium-90 (or other radiopharmaceuticals) within the past 3 months or major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access); with the exception of alopecia, all unresolved toxicities from prior treatment should be no greater than CTCAE grade 1 at the time of starting study treatment
4. Prior treatment with fulvestrant or everolimus
5. Prior treatment with PI3K inhibitors, Akt inhibitors or other mTOR inhibitors.
6. Patients receiving concomitant immunosuppressive agents or chronic systemic corticosteroids (≥10 mg prednisolone or an equivalent dose of other anti-inflammatory corticosteroids) use for ≥28 days at the time of study entry except in cases outlined below: Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed. Patients on stable low dose of corticosteroids for at least two weeks before randomisation are allowed
7. Current refractory nausea and vomiting, chronic gastrointestinal disease or inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of the study medication
8. Clinically significant pulmonary dysfunction
9. Significant cardiovascular disease
10. QTc prolongation defined as a QTc interval \>470 msecs or other significant ECG abnormalities including 2nd degree (type II) or 3rd degree AV block or bradycardia (ventricular rate \<50 beats/min)
11. Concomitant medications known to prolong QT interval, or with factors that increase the risk of QTc prolongation or risk of arrhythmic events (such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age)
12. Clinically significant abnormalities of glucose metabolism
13. Exposure to potent or moderate inhibitors or inducers of CYP3A4/5 within 2 weeks before the first dose of study treatment
14. Exposure to potent or moderate inhibitors or inducers of CYP2C8 within 1 week before the first dose of study treatment.
15. Application of haemopoietic growth factors (e.g. G-CSF, GM-CSF) within 2 weeks before receiving study drug
16. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.
17. History of hypersensitivity to active or inactive excipients of AZD2014 or everolimus or drugs with a similar chemical structure or class to AZD2014 or everolimus
18. History of hypersensitivity to active or inactive excipients of fulvestrant and/or castor oil.
19. Patients presenting with anaemia symptoms (haemoglobin ≤ 90 g/L).
20. Currently receiving (and are unwilling to discontinue) oestrogen replacement therapy (last dose ≤ 7 days prior to randomisation)
21. Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol.
22. Detained persons or prisoners
23. Pregnant or nursing women (including no breast feeding from two weeks before the first dose of study medication, till 8 weeks after the last dose of study medication).
18 Years
FEMALE
No
Sponsors
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AstraZeneca
INDUSTRY
Queen Mary University of London
OTHER
Responsible Party
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Principal Investigators
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Peter Schmid, Prof
Role: PRINCIPAL_INVESTIGATOR
Queen Mary's University of London
Locations
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ICO Paul Papin
Angers, , France
Institut Sainte Catherine
Avignon, , France
Antoine Lacassagne Centre De Lutte Contre Le Cancer De Nice
Nice, , France
Hospital Center Private Saint-Grégoire
Saint-Grégoire, , France
Centre Paul Strauss
Strasbourg, , France
Clinic Health House
Tbilisi, , Georgia
Institute of Clinical Oncology
Tbilisi, , Georgia
S. Khechinashvili University Clinic
Tbilisi, , Georgia
Tbilisi Cancer Center
Tbilisi, , Georgia
Frauenärztliche Gemeinschaftspraxis - Onkologie
Braunschweig, , Germany
Kliniken Essen-Mitte Senologie
Essen, , Germany
Klinik für Gynäkologie & Geburtshilfe/Brustzentrum
Frankfurt, , Germany
Praxis für interdisziplinäre Onkologie & Hämatologie
Freiburg im Breisgau, , Germany
MediProjekt GbR Hannover
Hannover, , Germany
SLK-Kliniken Heilbronn GmbH
Heilbronn, , Germany
Dokusan GmbH
Herne, , Germany
St. Vincentius Kliniken
Karlsruhe, , Germany
Schwerpunktpraxis Hämatologie / Onkologie MVZ Lahr
Lahr, , Germany
Klinikum Neumarkt
Neumarkt, , Germany
Onkologische Praxis
Oldenburg, , Germany
Praxis für Innere Medizin
Singen, , Germany
MVZ Klinik Dr. Hancken GmbH
Stade, , Germany
Mutterhaus der Borromäerinnen
Trier, , Germany
Schwarzwald Baar Klinikum, Villingen-Schwenningen
Villingen-Schwenningen, , Germany
Uzsoki Street Hospital
Budapest, , Hungary
Bacs-Kiskun County Hospital
Kalocsa, , Hungary
University of Pecs, Institute of Oncology
Pécs, , Hungary
Zala County Szent Rafael Hospital
Zalaegerszeg, , Hungary
Hospital da Luz
Lisbon, , Portugal
Ipo Porto
Porto, , Portugal
Center of Oncology Euroclinic
Bucharest, , Romania
Oncology Center Sf Nectarie
Caracal, , Romania
Cluj County Clinical Emergency Hospital, Clinical Department of Medical Oncology
Cluj-Napoca, , Romania
Oncology Institute "Prof. Dr. Ion Chiricuta"
Cluj-Napoca, , Romania
Oncology Center Oncolab Craiova
Craiova, , Romania
National Cancer Center South Korea
Goyang, , South Korea
Korea University Medical Center Guro Hospital
Seoul, , South Korea
Yonsei University Health System
Seoul, , South Korea
Hospital Universitari Vall D'Hebron
Barcelona, , Spain
Instituto Oncologico Dr. Rosell
Barcelona, , Spain
Consorcio Hospitalario Provincial de Castellon
Castelló, , Spain
Cafeteria Hospital San Pedro de Alcantara
Cáceres, , Spain
Hospital Ico Josep Trueta
Girona, , Spain
University Hospital Arnau de Vilanova
Lleida, , Spain
Hospital Clinico Universitario San Carlos
Madrid, , Spain
Hospital Son Llàtzer
Palma, , Spain
Hospital Son Espases
Palma de Mallorca, , Spain
Hospital Universitario de Canarias
San Cristóbal de La Laguna, , Spain
Hospital Universitari Sant Joan de Reus
Tarragona, , Spain
Wansbeck General Hospital
Ashington, , United Kingdom
Princess of Wales Hospital
Bridgend, , United Kingdom
Royal Sussex County Hospital
Brighton, , United Kingdom
Kent and Canterbury Hospital
Canterbury, , United Kingdom
Cumberland Infirmary
Carlisle, , United Kingdom
Broomfield Hospital
Chelmsford, , United Kingdom
University Hospital of North Durham
Durham, , United Kingdom
Calderdale Royal Hospital
Halifax, , United Kingdom
Huddersfield Royal Infirmary
Huddersfield, , United Kingdom
Kidderminster Hospital
Kidderminster, , United Kingdom
Royal Glamorgan Hospital
Llantrisant, , United Kingdom
Queen Mary University of London
London, , United Kingdom
Charring Cross Hospital
London, , United Kingdom
King's College Hospital
London, , United Kingdom
Mount Vernon Hospital
London, , United Kingdom
Queen Elizabeth Hospital, Woolwich
London, , United Kingdom
Saint Bartholomew's Hospital
London, , United Kingdom
The Royal Free Hospital
London, , United Kingdom
The Kent Oncology Centre
Maidstone, , United Kingdom
North Tyneside General Hospital
North Shields, , United Kingdom
Nottingham City Hospital
Nottingham, , United Kingdom
Derriford Hospital
Plymouth, , United Kingdom
Weston Park Hospital
Sheffield, , United Kingdom
Solihull Hospital
Solihull, , United Kingdom
Southend University Hospital
Southend-on-Sea, , United Kingdom
Royal Stoke University Hospital
Stoke-on-Trent, , United Kingdom
King's Mill Hospital
Sutton in Ashfield, , United Kingdom
Great Western Hospital
Swindon, , United Kingdom
Wrexham Maelor
Wrexham, , United Kingdom
Yeovil District Hospital
Yeovil, , United Kingdom
Countries
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References
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Schmid P, Zaiss M, Harper-Wynne C, Ferreira M, Dubey S, Chan S, Makris A, Nemsadze G, Brunt AM, Kuemmel S, Ruiz I, Perello A, Kendall A, Brown J, Kristeleit H, Conibear J, Saura C, Grenier J, Mahr K, Schenker M, Sohn J, Lee KS, Shepherd CJ, Oelmann E, Sarker SJ, Prendergast A, Marosics P, Moosa A, Lawrence C, Coetzee C, Mousa K, Cortes J. Fulvestrant Plus Vistusertib vs Fulvestrant Plus Everolimus vs Fulvestrant Alone for Women With Hormone Receptor-Positive Metastatic Breast Cancer: The MANTA Phase 2 Randomized Clinical Trial. JAMA Oncol. 2019 Nov 1;5(11):1556-1564. doi: 10.1001/jamaoncol.2019.2526.
Other Identifiers
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009175QM
Identifier Type: -
Identifier Source: org_study_id