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