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History of Changes for Study: NCT02299999
Evaluation of the Efficacy of High Throughput Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (SAFIR02_Breast)
Latest version (submitted March 8, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 November 20, 2014 None (earliest Version on record)
2 November 16, 2015 Study Status and Sponsor/Collaborators
3 February 19, 2016 Contacts/Locations, Arms and Interventions, Outcome Measures, Study Description, Study Status, Study Identification, IPDSharing, References and Eligibility
4 May 2, 2017 Study Status, Contacts/Locations, Study Design and Study Description
5 September 28, 2018 Contacts/Locations and Study Status
6 October 18, 2018 Contacts/Locations and Study Status
7 February 25, 2019 Arms and Interventions, Study Status, Eligibility and Study Description
8 October 3, 2019 Recruitment Status, Study Status, Contacts/Locations and Study Design
9 April 16, 2020 Study Status
10 August 24, 2020 Study Status, Contacts/Locations and Study Description
11 September 8, 2021 Study Status
12 March 8, 2022 Study Status
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Study NCT02299999
Submitted Date:  November 20, 2014 (v1)

Open or close this module Study Identification
Unique Protocol ID: UC-0105/1304
Brief Title: Evaluation of the Efficacy of High Throughput Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (SAFIR02_Breast)
Official Title: Evaluation of the Efficacy of High Throughput Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer
Secondary IDs: 2013-001652-36 [EudraCT Number]
Open or close this module Study Status
Record Verification: November 2014
Overall Status: Recruiting
Study Start: April 2014
Primary Completion: October 2016 [Anticipated]
Study Completion: October 2018 [Anticipated]
First Submitted: October 1, 2014
First Submitted that
Met QC Criteria:
November 20, 2014
First Posted: November 24, 2014 [Estimate]
Last Update Submitted that
Met QC Criteria:
November 20, 2014
Last Update Posted: November 24, 2014 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: UNICANCER
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: This is an open label multicentric phase II randomized trial, using high throughput genome analysis as a therapeutic decision tool, which aims at comparing a targeted treatment administered according to the identified molecular anomalies of the tumor with maintenance chemotherapy
Detailed Description:
Open or close this module Conditions
Conditions: Metastatic Breast Cancer
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 460 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Targeted Agent
Arm A / Targeted Arm : targeted maintenance from a list of 8 targeted drugs guided by the genomic analysis, AZD2014 tablet per os 50 mg bd, continuous dosing, AZD4547 tablet per os 80 mg bd, 2 weeks on/1 week off, AZD5363 capsule per os 480 mg bd, 4 days on/3 days off, AZD8931 tablet per os 40 mg bd, continuous dosing, selumetinib capsule per os 75 mg bd, continuous dosing, vandetanib tablet per os 300 mg od, continuous dosing, bicalutamide tablet per os 150 od, continuous dosing, olaparib tablet per os 300 mg bd, continuous dosing
Drug: AZD2014
Target : m-TOR
Drug: AZD4547
Target : EGFR
Drug: AZD5363
Target : AKT
Drug: AZD8931
Target : HER2, EGFR
Drug: Selumetinib
target : MEK
Other Names:
  • ARRY-142866
Drug: Vandetanib
target : VEGF, EGFR
Other Names:
  • CAPRELSA
Drug: Bicalutamide
target : Androgen receptor
Other Names:
  • Casodex
Drug: Olaparib
Target : PARP
Other Names:
  • Lynparza
Active Comparator: Maintenance Standard Chemotherapy
Arm B/ maintenance Standard Chemotherapy Arm : such as Anthracyclines (Doxorubicine or Epirubicine or Liposomal Doxorubicine), Taxanes (Paclitaxel, Docetaxel), Cyclophosphamide, DNA Intercalators (Capecitabine, 5-FU, gemcitabine), Methotrexate, Vinca alkaloids (Vinorelbine, Vinblastine, Vincristine), Platinum based chemotherapies (Carboplatin, Cisplatin), Bevacizumab, Mitomycine C, Eribuline
Drug: Anthracyclines
Other Names:
  • Doxorubicin, Epirubicin, liposomal doxorubicin
Drug: Taxanes
Other Names:
  • paclitaxel
  • docetaxel
Drug: cyclophosphamide
Other Names:
  • Novatrex
  • Imeth
Drug: DNA intercalators
Other Names:
  • capecitabine
  • 5-FU
  • gemcitabine
Drug: MethotrexateDrug: vinca alkaloids
Other Names:
  • vinorelbine
  • vinblastine
  • vincristine
Drug: Platinum based chemotherapies
Other Names:
  • Platinum
  • carboplatin
  • cisplatin
Drug: Bevacizumab
Other Names:
  • Avastin
Drug: Mitomycine C
Other Names:
  • Ametycine
Drug: Eribuline
Other Names:
  • Halaven
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Progression-free survival in the targeted drug arm compared to standard maintenance therapy arm
[ Time Frame: from randomization to disease progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months) ]

To evaluate whether treatment with targeted agents guided by high throughput molecular analysis (CGH array, next generation sequencing) improves progression-free survival as compared to standard maintenance therapy in patients with metastatic Breast Cancer
Secondary Outcome Measures:
1. Overall survival in both arms
[ Time Frame: from randomization to death (any cause), up to 16 months ]

2. Overall disease response rates and changes in tumor size in both arms
[ Time Frame: tumor response is assessed every 21 days from treatment initiation until first progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months) ]

tumor response is defined as a complete or partial response, upon RECIST v1.1 criteria
3. Disease response rate for each evaluated drug
[ Time Frame: tumor response is assessed every 21 days from treatment initiation until first progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months) ]

tumor response is defined as a complete or partial response, upon RECIST v1.1 criteria
4. Number of patients presenting with acute or delayed toxicities to each drug
[ Time Frame: toxicities will be assessed during the whole treatment period (4 months expected in average) followed by a 1-year post-treatment follow-up period, and reported during the visits scheduled by the study flow chart ]

Toxicities are graded according to the CTCAE V4
5. Progression free and overall survival measured for each evaluated drug
[ Time Frame: from randomization to disease progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months) ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Women (or men) with histologically proven breast cancer.
  • Metastatic relapse or progression or stage IV at diagnosis.
  • No Her2 over-expression.
  • Patients with metastases that can be biopsied, except bone metastases
  • Patients who are eligible for a first or a second line of chemotherapy in metastatic setting (left to the discretion of investigators), or who are currently treated with a first or second line of chemotherapy with a maximum of 2 cycles at the time of biopsy. Screening of patients currently treated with a second line chemotherapy should have a stable disease.
  • For patients with ER+ disease, relapse or progression occurred during endocrine therapy, whatever the line, or less than 12 months after the end of endocrine therapy in adjuvant context
  • Age ≥ 18 years
  • WHO Performance Status 0/1
  • Presence of measurable target lesion according to RECIST criteria v1.1
  • Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
  • Patient with social insurance coverage. Inclusion Criteria Randomization
  • Patients who received 6 to 8 cycles of chemotherapy, or having received at least 4 cycles of chemotherapy definitively stopped for toxicity reasons, and who are presenting a stable or a responding disease at the time of randomization.
  • Patients who still meet the screening phase inclusion criteria and exclusion criteria.
  • Patients whose tumor sample is presenting at least one genomic alteration from the list of predefined targetable genomic alterations and for whom the multidisciplinary tumor board has provided a personalized guidance.
  • Age ≥ 25 years for patients planned to receive AZD4547.
  • Patients will have had at least a 28-day wash-out period from last chemotherapy administration prior to randomization and should have recover (grade ≤1) from all residual toxicities, excluding alopecia.
  • Potentially reproductive patients must agree to use an effective contraceptive method or practice adequate methods of birth control or practice complete abstinence while on treatment, beginning 2 weeks before the first dose of investigational product and for at least 4 months after the last dose of study drug.
  • Women of childbearing potential must have a negative serum pregnancy test done within 14 days of enrollment and/or urine pregnancy test 72 hours prior to the administration of the study drug.
  • Women who are breastfeeding should discontinue nursing prior to the first dose of study drug and until 3 months after the last dose.
  • Provision of signed and dated, written informed consent prior to randomization and to any study specific procedures, sampling and analysis.

Exclusion Criteria:

  • Spinal cord compression and/or symptomatic or progressive brain metastases (unless asymptomatic or treated and stable off steroids for at least 30 days prior to start of study drug).
  • Bone metastases when this is the only site of biopsiable disease
  • Patients with all target lesions in a previously irradiated region, except if clear progression has been observed prior to study in at least one of them
  • Patient who received more than 2 lines of chemotherapy at the time of the biopsy
  • Tumor progression observed with the current line of treatment when under 2nd line.
  • Abnormal coagulation contraindicating biopsy
  • Inability to swallow
  • Major problem with intestinal absorption
  • Any of the following cardiac criteria:

Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG Any factors increasing the risk of QTc prolongation or arrhythmic events such as heart failure, hypokalaemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years old or any concomitant medication known to prolong the QT interval Experience of any of the following procedures or conditions in the preceding 12 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, past or current uncontrolled angina pectoris (Canadian Cardiovascular Society grade II-IV despite medical therapy), congestive heart failure NYHA Grade ≥2, torsades de pointes, current uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy), cardiomyopathy

  • Past medical history of interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis which requires steroïd treatment or any evidence of clinically interstitial lung disease
  • Previous or current malignancies of other histologies within the last 5 years, with the exception of in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin.
  • Evidence of severe or uncontrolled systemic disease (active bleeding diatheses, or active Hepatitis B, C and HIV)
  • Diagnosis of diabetes mellitus type I or II (irrespective of management)
  • Medical diagnosis of acne rosacea, severe psoriasis and severe atopic eczema
  • Prior exposure to anthracyclines or mitoxantrone with cumulative exposure in excess of 360 mg/m² for doxorubicin, 720 mg/m² for epirubicin, or 72 mg/m² for mitoxantrone.
  • History of retinal degenerative disease, eye injury or corneal surgery in the previous 3 months, past history of central serous retinopathy or retinal vein occlusion, intraocular pressure >21 mmHg, or uncontrolled glaucoma.
  • Women who are pregnant.
  • History of hemorrhagic or thrombotic stroke, TIA or other CNS bleeds
  • Renal disease including glomerulonephritis, nephritic syndrome, Fanconi syndrome, renal tubular acidosis.
  • Previous history of myelodysplastic syndrome
  • Patients using drugs that are known potent inhibitors or potent inducers or substrates of cytochrome P450 are not eligible if those treatments cannot be substituted during the randomized phase of the study.
  • Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol.
  • Individuals deprived of liberty or placed under the authority of a tutor Exclusion criteria for randomization
  • No "targetable" genomic alteration identified during the screening phase (either due to the lack of alteration or due to ineligible samples for genomic analysis) or unfavorable decision from the multidisciplinary tumor board to drive the patient to the randomization.
  • More than 2 previous lines of chemotherapy for metastatic disease before randomization.
  • Life expectancy < 3 months.
  • Disease progression occuring at any time during chemotherapy and before randomization or toxicity that led to the discontinuation of the last chemotherapy before 4 full cycles have been delivered.
  • Major surgery within 30 days (excluding placement of vascular access) or minor surgery within 14 days prior to randomisation.
  • Less than 28 days from radiotherapy (wide field of radiation), less than 2 weeks from palliative radiation (limited fields). Fields should not have involved all target lesions.
  • Patients treated in the last 30 days with a targeted agent in the same class as agents tested in this study.
  • Participation to another clinical study with an investigational product (IP) during the last 30 days.
  • History of hypersensitivity to active or inactive excipients of the study drug.
  • Toxicities of grade ≥2 from any previous anti-cancer therapy, with the exception of alopecia.
  • Altered haematopoietic or organ function, as indicated by the following criteria:
  • Polynuclear neutrophils < 1.5 x 109/L
  • Platelets < 100 x 109/L
  • Haemoglobin < 90 g/L
  • ALAT/ASAT > 2.5x ULN in the absence of or > 5x ULN in the presence of liver metastases
  • Bilirubin > 1.5xULN
  • Creatinine clearance ≤50 mL/min (measured or calculated by Cockroft and Gault formula)
  • Proteinuria > 3+ on dipstick analysis or > 3.5g/24 hours or a urine protein/creatinine ratio > 3.5 (only for patients drived to receive AZD5363)
  • Sodium, magnesium, calcium and phosphate > ULN
  • Potassium < 4 mmol/L
  • Glycosylated haemoglobin (HbA1C) ≥ 8.0% (64 mmol/mol), (only for patients supposed to receive AZD5363)
  • Fasting Plasma Glucose ≥ 7.0 mmol/L(126 mg/dL) (fasting is defined as no calorie intake for at least 8 hours)
  • Any of the following additional cardiac criteria:
  • Mean resting corrected QT interval (QTc)>480msec (or QTcF >450 msec) obtained from 3 consecutive ECGs
  • LVEF <55% (MUGA scan or Echocardiogram).
  • Altered ophthalmic conditions confirmed by an ophthalmology specialist for patients likely to be treated with :
  • AZD4547 : current evidence or previous history of retinal pigmented epithelium detachment (RPED), previous laser treatment or intra-ocular injection for treatment of macular degeneration, current evidence or previous history of dry or wet age-related macular degeneration, current evidence or previous history of retinal vein occlusion (RVO), current evidence or previous history of retinal degenerative diseases (eg, hereditary), current evidence or previous history of any other clinically relevant chorioretinal defect
  • AZD8931 : any eye injury in the previous 3 months or a prior eye injury still associated with persistent or recurrent symptoms or impairment of vision, corneal surgery (laser refractive surgery performed more than 3 months prior to the start of the trial is allowed and should be recorded in surgical history), orbital irradiation, collagen vascular, chronic inflammatory or degenerative disease with eye involvement (eg, rheumatoid, Sjögren's syndrome, systemic lupus erythematosus [SLE]), clinically significant ocular surface disease i.e. diseases of the conjunctiva and cornea (including atopic keratoconjunctivitis, Stevens Johnson syndrome, ocular cicatricial pemphigoid or chemical burns, Herpes simplex or Herpes zoster virus eye disease), evidence of maculopathy in patients with impaired visual acuity (impaired visual acuity is defined as best corrected near visual acuity <0.4 or best corrected distance visual acuity (including with pinhole) <0.7).
  • Selumetinib : intraoccular pressure >21 mmHg, or uncontrolled glaucoma (irrespective of intraocular pressure), current or past history of central serous retinopathy or retinal vein occlusion.
  • Patients using drugs that are known potent inhibitors or potent inducers or substrates of cytochrome P450 are not eligible if those treatments cannot be substituted from 14 days prior to the first dose (except those for which the minimum wash-out period is longer, e.g. Fluoxetine and Phenobarbital: 5 weeks, Rifabutin : 3 weeks and amiodarone: 27 weeks) and during the study.
  • Patients using non-substitutable drugs, that are known to prolong QT interval or induce Torsades de Pointes, from 14 days prior to the first dose (except those for which the minimum wash-out period is longer) and during the study, are not eligible when they are supposed to be treated with vandetanib, AZD5363 or AZD8931
Open or close this module Contacts/Locations
Central Contact Person: Sophie VERRIER, PhD
Telephone: 01 71 93 63 64
Email: s-verrier@unicancer.fr
Study Officials: Fabrice ANDRE, Pr
Principal Investigator
Gustave Roussy, Villejuif
Locations: France
Institut Sainte-Catherine
[Active, not recruiting]
Avignon, France
Institut Bergonié
[Recruiting]
Bordeaux, France
Contact:Contact: Hervé Bonnefoi h.bonnefoi@bordeaux.unicancer.fr
Contact:Principal Investigator: Hervé Bonnefoi, MD
Centre François Baclesse
[Recruiting]
Caen, France
Contact:Contact: Christelle Lévy c.levy@baclesse.unicancer.fr
Contact:Principal Investigator: Christelle Lévy, MD
Centre Jean Perrin
[Recruiting]
Clermont-Ferrand, France
Contact:Contact: Marie-Ange Mouret Reynier marie-ange.mouret-reynier@cjp.fr
Contact:Principal Investigator: Marie-Ange Mouret Reynier, MD
Centre Georges François Leclerc
[Recruiting]
Dijon, France, 21079
Contact:Contact: Nicolas Isambert nisambert@cgfl.fr
Contact:Principal Investigator: Nicolas Isambert, MD
Centre Oscar Lambret
[Recruiting]
Lille, France
Contact:Contact: Géraldine Lauridant g-lauridant@o-lambret.fr
Contact:Principal Investigator: Géraldine Lauridant, MD
Centre Hospitalier Lyon Sud
[Active, not recruiting]
Lyon, France
Centre Léon Bérard
[Recruiting]
Lyon, France
Contact:Contact: Thomas Bachelot thomas.bachelot@lyon.unicancer.fr
Contact:Principal Investigator: Thomas Bachelot, MD
Institut Paoli Calmettes
[Recruiting]
Marseille, France
Contact:Contact: Anthony Gonçalves goncalvesa@ipc.unicancer.fr
Contact:Principal Investigator: Anthony Gonçalves, MD
Institut Régional du Cancer Montpellier Val d'Aurelle
[Recruiting]
Montpellier, France
Contact:Contact: William Jacot william.jacot@icm.unicancer.fr
Contact:Principal Investigator: William Jacot, MD
Centre Alexis Vautrin
[Recruiting]
Nancy, France
Contact:Contact: Elisabeth Luporsi e.luporsi@nancy.unicancer.fr
Contact:Principal Investigator: Elisabeth Luporsi, MD
Institut de Cancérologie de l'Ouest/ René Gauducheau
[Recruiting]
Nantes, France
Contact:Contact: Mario Campone mario.campone@ico.unicancer.fr
Contact:Principal Investigator: Mario Campone, MD
Centre Antoine Lacassagne
[Recruiting]
Nice, France
Contact:Contact: Jean-Marc Ferrero jean-marc.ferrero@nice.unicancer.fr
Contact:Principal Investigator: Jean-Marc Ferrero, MD
Institut Curie
[Recruiting]
Paris, France
Contact:Contact: Marie-Paule Sablin mariepaule.sablin@curie.fr
Contact:Principal Investigator: Marie-Paule Sablin, MD
Centre Eugène Marquis
[Recruiting]
Rennes, France
Contact:Contact: Claudia Lefeuvre-Plesse c.lefeuvre@rennes.unicancer.fr
Contact:Principal Investigator: Claudia Lefeuvre-Plesse, MD
Centre Henri Becquerel
[Recruiting]
Rouen, France
Contact:Contact: Jean-Christophe Théry jean-christophe.thery@chb.unicancer.fr
Contact:Principal Investigator: Jean-Christophe Théry, MD
Institut Curie
[Active, not recruiting]
Saint-Cloud, France
Institut Claudius Regaud
[Recruiting]
Toulouse, France
Contact:Contact: Florence Dalenc, MD dalenc.florence@iuct-oncopole.fr
Contact:Principal Investigator: Florence Dalenc, MD
Gustave Roussy
[Recruiting]
Villejuif, France
Contact:Contact: Monica Arnedos Monica.ARNEDOS@gustaveroussy.fr
Contact:Principal Investigator: Monica Arnedos, MD
Contact:Sub-Investigator: Fabrice André, MD
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links: Description: Related Info
Description: SAFIR01 study results
Available IPD/Information:

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