Clinical trials in breast cancer in Clinical trials in breast cancer in Italy: the Gruppo Italiano Mammella Italy: the Gruppo Italiano Mammella

(GIM)(GIM)

Lucia Del MastroLucia Del MastroIstituto Nazionale per la Ricerca sul Istituto Nazionale per la Ricerca sul

Cancro Genoa – ItalyCancro Genoa – ItalyRoma, 16 Novembre 2006Roma, 16 Novembre 2006

GIM groupGIM group

• Intergroup:Intergroup: GONO-GOCSI-GOIRC-GOL• Participating centers: 100 italian 100 italian

centerscenters• Main focus: phase III study in early

breast cancer– ChemotherapyChemotherapy– Endocrine therapy– Supportive careSupportive care

Adjuvant chemotherapy Adjuvant chemotherapy trialstrials

• Role ofRole of taxanes taxanes inin node negative node negative patientspatients– GIM-1 studyGIM-1 study

• Role ofRole of dose-densedose-dense and role ofand role of three-three-drug regimen as compared to two-drug regimen as compared to two-drugdrug regimen in taxane-containing regimen in taxane-containing chemotherapy in chemotherapy in node positive patientsnode positive patients– GIM-2 studyGIM-2 study

GIM 1 studyGIM 1 study

A phase III randomized study of sequential A phase III randomized study of sequential Epidoxorubicin plus Cyclophospamide Epidoxorubicin plus Cyclophospamide

followed by Docetaxel followed by Docetaxel (EC(ECD)D) versus the versus the combination of combination of 5-Fluorouracil, 5-Fluorouracil,

Epidoxorubicin and Cyclophospamide Epidoxorubicin and Cyclophospamide (FEC)(FEC) as adjuvant treatment of as adjuvant treatment of node-negative node-negative

early breastearly breast cancercancer patients patients

GIM 1: phase III randomized studyGIM 1: phase III randomized study

FEC 600/FEC 600/7575/600 q21 x 6/600 q21 x 6EC EC 9090/600 q21 x 4/600 q21 x 4DOCETAXEL 100 q21 x 4 DOCETAXEL 100 q21 x 4

STUDY OBJECTIVESSTUDY OBJECTIVES

• Primary objective:

to compare Disease Free Survival (DFS) between treatment groups

• Secondary objective:

to compare Overall Survival (OS) to compare Safety

Study detailsStudy details

• Start date: 13/11/2003• Protocol status: ongoing• Participating centers: 84• Total randomized patients: 842

Protocol GIM 2Protocol GIM 2

A phase III randomized study of EC followed by Paclitaxel versus FEC

followed by Paclitaxel, all given either every 3 weeks or 2 weeks supported by Pegfilgrastim, for node positive

breast cancer patients

ARM DFEC x 4 T x 4 q. 2 w +

Pegfilgrastim

ARM BFEC x 4 T x 4 q. 3 w

ARM CEC x 4 T x 4 q. 2 w +

Pegfilgrastim

ARM AEC x 4 T x 4 q. 3 w

Factorial study aimed at assessing two separate hypothesis:

• Factor 1Factor 1: A+C vs B+D = the efficacy and safety of 5-FU in addition to ECT

GIM-2: study design and objectives

• Factor 2Factor 2: A+B vs C+D = the efficacy and safety of a 50% increase in dose-density

Study objectivesStudy objectives

• Primary objective: to compare Disease Free Survival

(DFS) from adding of 5-Fluorouracil to EC followed by Paclitaxel

to compare Disease Free Survival (DFS) of schedule every 2 weeks versus 3 weeks

• Secondary objective:

to compare Safety

Study detailsStudy details

• Start date: Start date: 20/03/200320/03/2003• Protocol status: Protocol status: closedclosed 03/07/200603/07/2006

• Participating centers:Participating centers: 91 91• Total randomized patients: Total randomized patients: 20912091

PROTOCOL GIM4PROTOCOL GIM4

LETROZOLE ADJUVANT THERAPY LETROZOLE ADJUVANT THERAPY DURATION STUDY (LEAD): DURATION STUDY (LEAD): STANDARD VERSUS LONG STANDARD VERSUS LONG

TREATMENT with AROMATASE TREATMENT with AROMATASE INHIBITORSINHIBITORS

A PHASE III STUDY IN A PHASE III STUDY IN POSTMENOPAUSAL WOMENPOSTMENOPAUSAL WOMEN WITH WITH

EARLY BREAST CANCEREARLY BREAST CANCER

Study designStudy design

Phase III randomized study• Postmenopausal• TAM 2-3 yrs

LETROZOLE 5 YRSLETROZOLE 5 YRS LETROZOLE 3-2 YRSLETROZOLE 3-2 YRS

Study objectives

• Primary objective: to compare Disease Free Survival

(DFS) between treatment groups

• Secondary objectives: to compare Overall Survival (OS) to compare Safety

Study detailsStudy details

• Start date: 27/07/05• Protocol status: ongoing• Participating centers: 64• Total randomized patients: 500

PROTOCOL GIM-5PROTOCOL GIM-5CYPLECCYPLEC STUDY: STUDY: CYPCYP19 19 LELETROZOLETROZOLE

CCORRELATION STUDYORRELATION STUDY

Letrozole Extended-Adjuvant Letrozole Extended-Adjuvant Therapy After TamoxifenTherapy After Tamoxifen

Study of Gene CYP19 Correlation Study of Gene CYP19 Correlation withwith Letrozole Efficacy in Postmenopausal Letrozole Efficacy in Postmenopausal

Early Breast Cancer PatientsEarly Breast Cancer Patients

CYPLEC – GIM 5CYPLEC – GIM 5 Multicenter, not comparative, Multicenter, not comparative,

prospective, phase IIIb study of GIM prospective, phase IIIb study of GIM groupgroup

PostmenopausPostmenopausal ptsal pts

ER and/or PgR ER and/or PgR ++

RegistratioRegistrationn

Letrozole Letrozole 5 years5 years

Tamoxifen Tamoxifen 4,5-6 yrs.4,5-6 yrs.

Total PatientsTotal Patients:: 2400 during a 3-year period2400 during a 3-year period

Primary objectivePrimary objective: correlation between a Single Nucleotide correlation between a Single Nucleotide Polymorphism (SNP) of CYP19 and Disease Free Survival (DFS)Polymorphism (SNP) of CYP19 and Disease Free Survival (DFS)

HypothesisHypothesis: 86% of power to detect a relative reduction of relapse 86% of power to detect a relative reduction of relapse of 46%of 46%: : 4-yrs DFS for TC genotype = 91%4-yrs DFS for TC genotype = 91%

4-yrs DFS for CC 4-yrs DFS for CC oror TT genotype = 95% TT genotype = 95%

Study objectivesStudy objectives

• PRIMARY OBJECTIVEPRIMARY OBJECTIVE Correlation Correlation DFS - SNP of CYP19DFS - SNP of CYP19 gene gene

• SECONDARY OBJECTIVESSECONDARY OBJECTIVES Correlation SNP of CYP19 gene and:Correlation SNP of CYP19 gene and: 1) 1) letrozoleletrozole plasma concentration plasma concentration 2) aromatase inhibition by plasma 2) aromatase inhibition by plasma

estrone-Sestrone-S 3) 3) OSOS 4) SafetySafety

Study detailsStudy details

• Start date: Start date: 27/07/0527/07/05

• Protocol status: Protocol status: ongoing ongoing

• Participating centers: Participating centers: 6464

• Total enrolled patients: Total enrolled patients: 162162

Protocol Promise

Prevention of chemotherapy – induced menopause by temporary ovarian

suppression with Triptorelin vs control in young breast cancer

patients.A randomized phase III multicenter

study

Study design

Randomized phase III study Age <45 yrs Stage I-II-III Candidate for chemotherapy

Only CTOnly CT CT + Triptorelin

Study ObjectivesStudy Objectives

• Primary objective:

to evaluate efficacy of Triptorelin to prevent chemotherapy-induced amennorreha

• Secondary objective: to compare safety of chemotherapy

associated to Triptorelin vs only chemotherapy

Study detailsStudy details

• Start date: Start date: 29/05/200329/05/2003

• Protocol status:Protocol status: ongoingongoing

• Participating Centers:Participating Centers: 2424• Total randomized patients: Total randomized patients: 188188