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

NCT02299999 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: UC-0105/13042013-001652-36
• Study Type: interventional
• Target: 1,460
• Locations: 1 country
• Sites: 25

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

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (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

  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)

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

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

• overall survival in each substudy

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

• overall response rates and changes in tumor size in each substudy

  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)

• evaluate safety, in each substudy

  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

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

  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)

Study Arms (4)

Substudy 1: targeted agent

EXPERIMENTAL

Arm 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

Drug: AZD2014; Drug: AZD4547; Drug: AZD5363; Drug: AZD8931; Drug: Selumetinib; Drug: Vandetanib; Drug: Bicalutamide; Drug: Olaparib

Substudy 1: standard maintenance therapy

ACTIVE COMPARATOR

Arm 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

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: Immunotherapy

EXPERIMENTAL

Arm 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

Drug: MEDI4736

Substudy 2: standard maintenance therapy

ACTIVE COMPARATOR

Arm 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

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

Interventions

AZD2014 DRUG

Target: m-TOR

Substudy 1: targeted agent

AZD4547 DRUG

Target: EGFR

Substudy 1: targeted agent

AZD5363 DRUG

Target: AKT

Substudy 1: targeted agent

AZD8931 DRUG

Target: HER2, EGFR

Substudy 1: targeted agent

Selumetinib DRUG

Target: MEK

Also known as: ARRY-142866

Substudy 1: targeted agent

Vandetanib DRUG

Target: VEGF, EGFR

Also known as: CAPRELSA

Substudy 1: targeted agent

Bicalutamide DRUG

target: Androgen receptor

Also known as: Casodex

Substudy 1: targeted agent

Olaparib DRUG

Target: PARP

Also known as: Lynparza

Substudy 1: targeted agent

Anthracyclines DRUG

DNA intercalation

Also known as: Doxorubicin, Epirubicin, liposomal doxorubicin

Substudy 1: standard maintenance therapy; Substudy 2: standard maintenance therapy

Taxanes DRUG

Target: mitotic tubulin and microtubules

Also known as: paclitaxel, docetaxel

Substudy 1: standard maintenance therapy; Substudy 2: standard maintenance therapy

cyclophosphamide DRUG

Alkylating agents

Also known as: Novatrex, Imeth

Substudy 1: standard maintenance therapy; Substudy 2: standard maintenance therapy

DNA intercalators DRUG

DNA intercalators

Also known as: capecitabine, 5-FU, gemcitabine

Substudy 1: standard maintenance therapy; Substudy 2: standard maintenance therapy

Methotrexate DRUG

DNA intercalators

Substudy 1: standard maintenance therapy; Substudy 2: standard maintenance therapy

vinca alkaloids DRUG

Target: mitotic tubulin and microtubules

Also known as: vinorelbine, vinblastine, vincristine

Substudy 1: standard maintenance therapy; Substudy 2: standard maintenance therapy

Platinum based chemotherapies DRUG

Platinum based chemotherapies

Also known as: Platinum, carboplatin, cisplatin

Substudy 1: standard maintenance therapy; Substudy 2: standard maintenance therapy

Bevacizumab DRUG

Target: VEGF

Also known as: Avastin

Substudy 1: standard maintenance therapy; Substudy 2: standard maintenance therapy

Mitomycin C DRUG

Alkylating agents

Also known as: Ametycine

Substudy 1: standard maintenance therapy; Substudy 2: standard maintenance therapy

Eribulin DRUG

Microtubule modulator

Also known as: Halaven

Substudy 1: standard maintenance therapy; Substudy 2: standard maintenance therapy

MEDI4736 DRUG

Target: PD-L1

Substudy 2: Immunotherapy

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• UNICANCER: lead
• Fondation ARC: collaborator
• AstraZeneca: collaborator

Study Sites (25)

Institut de Cancérologie de l'Ouest/Paul Papin

Angers, France

Location

Institut Sainte-Catherine

Avignon, France

Location

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, 33077, France

Location

Institut Bergonié

Bordeaux, France

Location

Centre François Baclesse

Caen, France

Location

Centre Jean Perrin

Clermont-Ferrand, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

Chd Vendee

La Roche-sur-Yon, 85925, France

Location

Centre Oscar Lambret

Lille, France

Location

Chu Dupuytren

Limoges, 87000, France

Location

Centre Hospitalier Lyon Sud

Lyon, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Institut Régional du Cancer Montpellier Val d'Aurelle

Montpellier, France

Location

Centre Alexis Vautrin

Nancy, France

Location

Institut de Cancérologie de l'Ouest/ René Gauducheau

Nantes, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Institut Curie

Paris, France

Location

Centre Eugène Marquis

Rennes, France

Location

Centre Henri Becquerel

Rouen, France

Location

Institut Curie

Saint-Cloud, France

Location

Hopitaux Universitaire de Strasbourg - Hopital Civil

Strasbourg, France

Location

Hopitaux Du Leman

Thonon-les-Bains, 74200, France

Location

Institut Claudius Regaud

Toulouse, France

Location

Gustave Roussy

Villejuif, France

Location

Related Publications (1)

• 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.

  PMID: 32067679 DERIVED

Related Links

• Unicancer official website
• SAFIR01 study results

MeSH Terms

Conditions

Breast Neoplasms

Interventions

vistusertib; AZD4547; capivasertib; AZD 8931; AZD 6244; vandetanib; bicalutamide; olaparib; Anthracyclines; Doxorubicin; Epirubicin; liposomal doxorubicin; Taxoids; Paclitaxel; Docetaxel; Cyclophosphamide; Methotrexate; Capecitabine; Fluorouracil; Gemcitabine; Vinca Alkaloids; Vinorelbine; Vinblastine; Vincristine; Platinum; Carboplatin; Cisplatin; Bevacizumab; Mitomycin; eribulin; durvalumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Daunorubicin; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals; Coordination Complexes; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Mitomycins; Indolequinones; Quinones; Azirines

Study Officials

• Fabrice ANDRE, Pr

  Gustave Roussy, Villejuif

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2014
• First Posted: November 24, 2014
• Study Start: April 7, 2014
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2025
• Last Updated: January 15, 2025

Record last verified: 2025-01

Locations

FR (25)