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Metastatic Breast CancerPhase 2SAFIR02_BreastNCT02299999

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer

A Phase 2 study testing AZD2014, AZD4547 and AZD5363 in people with Metastatic Breast Cancer, run by UNICANCER at 25 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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 (targeted substudy 1) as well as immunotherapy… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
AZD2014, AZD4547 and AZD5363
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,460 participants
Where
25 sitesFrance
Study dates
7 Apr 2014to Dec 2025
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 16Show fewer
  • Age ≥18 years
  • WHO Performance Status 0/1
  • Presence of measurable target lesion according to RECIST criteria v1.1
  • 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 SD or PR at randomization
  • presenting at least one genomic alteration from the predefined list
  • Age ≥25 years for patients planned to receive AZD4547
  • 28-day wash-out period from chemo prior to randomization and grade ≤1 residual toxicities
  • 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 SD or a RP at randomization
  • Patients not eligible to substudy 1
  • wash-out period of at least 15 days for weekly (except monoclonal antibodies) or daily chemotherapies or 28 days for other chemotherapies from last chemotherapy administration prior to randomization and grade ≤1 residual toxicities

Who cannot join

  • Spinal cord compression and/or symptomatic or progressive brain metastases
  • 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
  • Patients who already had a genomic profile (both CGH and NGS analysis) in which no SAFIR02 targetable alterations have been identified
Show all 39Show fewer
  • Abnormal coagulation contraindicating biopsy
  • Inability to swallow
  • Major problem with intestinal absorption Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG Any factors increasing the risk of QTc prolongation or arrhythmic events Experience of any of the following in the preceding 12 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, past or current uncontrolled angina pectoris, congestive heart failure NYHA Grade ≥2, torsades de pointes, current uncontrolled hypertension, cardiomyopathy Past medical history of interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis which requires steroid treatment or any evidence of clinically interstitial lung disease Previous or current malignancies of other histologies within the last 5 years, Evidence of severe or uncontrolled systemic disease (active bleeding diatheses, or active Hepatitis B, C and HIV)
  • 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
  • Previous treatment with the same agent or in the same class as one of those used in the SAFIR02 trial (patients who received this previous targeted agent without the target prescreening are eligible but may not be eligible for randomisation in substudy 1 if the treatment allocated by the MTB is in the same class) 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.
  • History of hemorrhagic or thrombotic stroke, TIA or other CNS bleeds
  • Renal disease including glomerulonephritis, nephritic syndrome, Fanconi syndrome, renal tubular acidosis
  • Patients using drugs that are known potent inhibitors or potent inducers or substrates of cytochrome P450
  • Randomized phase:
  • Substudy 1:
  • 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
  • Less than 28 days from radiotherapy, less than 2 weeks from palliative radiation
  • Patients previously treated with a targeted agent in the same class as the agent to be given to the patient in substudy 1
  • Toxicities of grade ≥2 from any previous anti-cancer therapy
  • Altered haematopoietic or organ function
  • Mean resting corrected QT interval (QTc) >480 msec (or QTcF >450 msec) obtained from 3 consecutive ECGs
  • Left ventricular ejection fraction (LVEF) <55% (MUGA scan or Echocardiogram)
  • Altered ophthalmic conditions confirmed by an ophthalmology specialist for patients likely to be treated with AZD4547 orAZD8931 or Selumetinib
  • Patients using non-substitutable drugs, that are known to prolong QT interval or induce Torsades de Pointes, when they are supposed to be treated with vandetanib, AZD5363 or AZD8931
  • Substudy 2:
  • 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
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including MEDI4736
  • Toxicities of grade ≥2 from any previous anti-cancer therapy
  • Altered haematopoietic or organ function
  • Mean resting QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 consecutive ECGs using Bazett's Correction
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of MEDI4736, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
  • Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
  • History of primary immunodeficiency

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

France25 sites

  • Institut de Cancérologie de l'Ouest/Paul Papin

    Angers

  • Institut Sainte-Catherine

    Avignon

  • Polyclinique Bordeaux Nord Aquitaine

    Bordeaux, 33077

  • Institut Bergonié

    Bordeaux

  • Centre François Baclesse

    Caen

  • Centre Jean Perrin

    Clermont-Ferrand

  • Centre Georges François Leclerc

    Dijon, 21079

  • Chd Vendee

    La Roche-sur-Yon, 85925

  • Centre Oscar Lambret

    Lille

  • Chu Dupuytren

    Limoges, 87000

  • Centre Hospitalier Lyon Sud

    Lyon

  • Centre Léon Bérard

    Lyon

  • Institut Paoli Calmettes

    Marseille

  • Institut Régional du Cancer Montpellier Val d'Aurelle

    Montpellier

  • Centre Alexis Vautrin

    Nancy

  • Institut de Cancérologie de l'Ouest/ René Gauducheau

    Nantes

  • Centre Antoine Lacassagne

    Nice

  • Institut Curie

    Paris

  • Centre Eugène Marquis

    Rennes

  • Centre Henri Becquerel

    Rouen

  • Institut Curie

    Saint-Cloud

  • Hopitaux Universitaire de Strasbourg - Hopital Civil

    Strasbourg

  • Hopitaux Du Leman

    Thonon-les-Bains, 74200

  • Institut Claudius Regaud

    Toulouse

  • Gustave Roussy

    Villejuif

Other trials in France

About this study

Official title: PERSONALIZED MEDICINE GROUP / UCBG UC-0105/1304: SAFIR02_Breast - Evaluation of the Efficacy of High Throughput Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer

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 (targeted substudy 1) as well as immunotherapy with maintenance chemotherapy in patients without actionable genomic alterations or non eligible to substudy 1 (immune substudy 2).

Read the detailed description

Screening phase:

New frozen biopsy or an archived frozen sample or ctDNA sample will be sent to the genomic platforms for DNA extraction and genomic analysis (DNA microarrays and Next generation sequencing).

Patients can be considered as pre-eligible for the targeted substudy 1 randomisation phase when both following mandatory conditions have been met: stable or responding disease has been observed (investigator judgment) after 6 to 8 cycles of chemotherapy (or at least after 4 cycles of chemotherapy if stopped for toxicity) and targetable alteration has been identified by the Molecular Tumor Board (MTB).

If not eligible for the substudy 1 randomisation phase, patients can be considered as pre-eligible for the immune substudy 2 randomization phase when both following mandatory conditions are met: stable or responding disease (investigator judgment) is observed after 6 to 8 cycles of chemotherapy (or at least after 4 cycles if treatment was stopped due to toxicity) AND not eligible to randomization in the substudy 1 (because patient had no targetable alteration identified by the Molecular Tumor Board, or failed to have a genomic profile for the tumor [low tumor cells percentage, technical issue during genomic analysis, etc.], or a non inclusion criteria that precluded entry into the substudy 1)

Randomization phase:

The mandatory post-chemotherapy wash-out period, of 28 days for 21 or 28 day-cycle chemotherapies or of 15 days for weekly (except monoclonal antibodies) or daily chemotherapies,will provide time to achieve all the required tests and examinations.

The randomization program will allocate the following treatments with a 2:1 ratio in favor of Arm A of the considered substudy:

Substudy 1 : targeted therapies versus standard maintenance chemotherapy

  • Arm A1 / targeted arm: targeted maintenance from a list of 8 targeted drugs guided by the genomic analysis, or
  • Arm B1 / chemotherapy arm : maintenance chemotherapy (or no antineoplastic treatment in case of toxicity at the time of randomization)

Substudy 2 : immunotherapy versus standard maintenance chemotherapy

  • Arm A2 / immunotherapy maintenance arm: MEDI4736 or
  • Arm B2 / chemotherapy arm: chemotherapy continued as a maintenance chemotherapy (or no antineoplastic treatment in case of toxicity)
Being tested
AZD2014, AZD4547, AZD5363, AZD8931, Selumetinib
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD2014Drug

    Target: m-TOR

  • AZD4547Drug

    Target: EGFR

  • AZD5363Drug

    Target: AKT

  • AZD8931Drug

    Target: HER2, EGFR

  • SelumetinibDrug

    Also called ARRY-142866

    Target: MEK

  • VandetanibDrug

    Also called CAPRELSA

    Target: VEGF, EGFR

  • BicalutamideDrug

    Also called Casodex

    target: Androgen receptor

  • OlaparibDrug

    Also called Lynparza

    Target: PARP

  • AnthracyclinesDrug

    Also called Doxorubicin, Epirubicin, liposomal doxorubicin

    DNA intercalation

  • TaxanesDrug

    Also called paclitaxel, docetaxel

    Target: mitotic tubulin and microtubules

  • cyclophosphamideDrug

    Also called Novatrex, Imeth

    Alkylating agents

  • DNA intercalatorsDrug

    Also called capecitabine, 5-FU, gemcitabine

    DNA intercalators

  • MethotrexateDrug

    DNA intercalators

  • vinca alkaloidsDrug

    Also called vinorelbine, vinblastine, vincristine

    Target: mitotic tubulin and microtubules

  • Platinum based chemotherapiesDrug

    Also called Platinum, carboplatin, cisplatin

    Platinum based chemotherapies

  • BevacizumabDrug

    Also called Avastin

    Target: VEGF

  • Mitomycin CDrug

    Also called Ametycine

    Alkylating agents

  • EribulinDrug

    Also called Halaven

    Microtubule modulator

  • MEDI4736Drug

    Target: PD-L1

Study groups in NCT02299999
Study groupRoleWhat they receive
Substudy 1: targeted agentExperimentalArm A1 / 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
Receives: Drug: AZD2014; Drug: AZD4547; Drug: AZD5363; Drug: AZD8931; Drug: Selumetinib; Drug: Vandetanib; Drug: Bicalutamide; Drug: Olaparib
Substudy 1: standard maintenance therapyActive comparatorArm B1/ maintenance Standard Chemotherapy Arm : such as Anthracyclines (Doxorubicin or Epirubicin 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, Mitomycin C, Eribulin
Receives: Drug: Anthracyclines; Drug: Taxanes; Drug: cyclophosphamide; Drug: DNA intercalators; Drug: Methotrexate; Drug: vinca alkaloids; Drug: Platinum based chemotherapies; Drug: Bevacizumab; Drug: Mitomycin C; Drug: Eribulin
Substudy 2: ImmunotherapyExperimentalArm A2/ Immunotherapy arm: maintenance with MEDI4736 for patient without actionable genomic alterations or non eligible to Targeted substudy 1, MEDI4736 Intra-venous 10 mg/kg, Q2W
Receives: Drug: MEDI4736
Substudy 2: standard maintenance therapyActive comparatorArm B2/ maintenance Standard Chemotherapy Arm : such as Anthracyclines (Doxorubicin or Epirubicin 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, Mitomycin C, Eribulin
Receives: Drug: Anthracyclines; Drug: Taxanes; Drug: cyclophosphamide; Drug: DNA intercalators; Drug: Methotrexate; Drug: vinca alkaloids; Drug: Platinum based chemotherapies; Drug: Bevacizumab; Drug: Mitomycin C; Drug: Eribulin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival in the targeted drug arm compared to standard maintenance therapy arm

    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

    Measured: from randomization to disease progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months)

Secondary outcomes (6)

  1. progression-free survival in patients treated with anti-PDL1 antibody (MEDI4736) compared to standard maintenance therapy arm

    To evaluate whether treatment with MEDI4736 improves progression-free survival as compared to standard maintenance therapy in patients with metastatic Breast Cancer

    Measured: from randomization to disease progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months)

  2. overall survival in each substudy

    To evaluate whether treatment with targeted agents guided by high throughput molecular analysis (CGH array, next generation sequencing) or MEDI4736 improves overall survival as compared to standard maintenance therapy in patients with metastatic Breast Cancer

    Measured: from randomization to death (any cause), up to 16 months

  3. overall response rates and changes in tumor size in each substudy

    tumor response is defined as a complete or partial response, upon RECIST v1.1 criteria

    Measured: 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)

  4. evaluate safety, in each substudy

    Toxicities are graded according to the CTCAE V4

    Measured: 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

  5. efficacy (response rate, change in tumor size, progression-free survival, overall survival) and safety of each individual targeted agent (substudy 1)

    tumor response is defined as a complete or partial response, upon RECIST v1.1 criteria

    Measured: 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)

  6. correlate molecular characteristics in patients with the efficacy endpoints (response rate, progression-free and overall survival) in each substudy

    tumor response is defined as a complete or partial response, upon RECIST v1.1 criteria

    Measured: from randomization or treatment initiation to disease progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Nov 2014 (estimated)
  2. Study start7 Apr 2014
  3. Primary completionDec 2022
  4. Study completionDec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,460 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02299999
Sponsor's protocol ID
UC-0105/1304
Other IDs
2013-001652-36
Acronym
SAFIR02_Breast
Status last verified
Jan 2025
First submitted
1 Oct 2014
Last updated
15 Jan 2025
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Mosele F, Stefanovska B, Lusque A, Tran Dien A, Garberis I, Droin N, Le Tourneau C, Sablin MP, Lacroix L, Enrico D, Miran I, Jovelet C, Bieche I, Soria JC, Bertucci F, Bonnefoi H, Campone M, Dalenc F, Bachelot T, Jacquet A, Jimenez M, Andre F. Outcome and molecular landscape of patients with PIK3CA-mutated metastatic breast cancer. Ann Oncol. 2020 Mar;31(3):377-386. doi: 10.1016/j.annonc.2019.11.006. Epub 2020 Jan 24.

    PubMed 32067679

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AZD2014, AZD4547 and AZD5363 in people with Metastatic Breast Cancer, run by UNICANCER at 25 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 15 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02299999, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2025.

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