1. Istituto Nazionale per la Ricerca sul Cancro Genoa – Italy
Clinical trials in breast cancer in Italy: the Gruppo Italiano Mammella (GIM)
Lucia Del Mastro
Istituto Nazionale per la Ricerca sul Cancro Genoa – Italy
Roma, 16 Novembre 2006

2. GIM group Intergroup: GONO-GOCSI-GOIRC-GOL
Participating centers: 100 italian centers
Main focus: phase III study in early breast cancer
Chemotherapy
Endocrine therapy
Supportive care

3. Adjuvant chemotherapy trials
Role of taxanes in node negative patients
GIM-1 study
Role of dose-dense and role of three-drug regimen as compared to two-drug regimen in taxane-containing chemotherapy in node positive patients
GIM-2 study

4. GIM 1 study
A phase III randomized study of sequential Epidoxorubicin plus Cyclophospamide followed by Docetaxel (ECD) versus the combination of 5-Fluorouracil, Epidoxorubicin and Cyclophospamide (FEC) as adjuvant treatment of node-negative early breast cancer patients

5. GIM 1: phase III randomized study
EC 90/600 q21 x 4
DOCETAXEL 100 q21 x 4
FEC 600/75/600 q21 x 6

6. STUDY OBJECTIVES Primary objective: Secondary objective:
to compare Disease Free Survival (DFS) between treatment groups
Secondary objective:
to compare Overall Survival (OS)
to compare Safety

7. Study details Start date: 13/11/2003 Protocol status: ongoing
Participating centers:
Total randomized patients:

8. Protocol 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

9. GIM-2: study design and objectives
ARM A
EC x 4  T x 4 q. 3 w
ARM C
EC x 4  T x 4 q. 2 w + Pegfilgrastim
ARM B
FEC x 4  T x 4 q. 3 w
ARM D
FEC x 4  T x 4 q. 2 w + Pegfilgrastim
Factorial study aimed at assessing two separate hypothesis:
Factor 1: A+C vs B+D = the efficacy and safety of 5-FU in addition to ECT
Factor 2: A+B vs C+D = the efficacy and safety of a 50% increase in dose-density

10. Study objectives Primary objective: Secondary 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

11. Study details Start date: 20/03/2003
Protocol status: closed 03/07/2006
Participating centers:
Total randomized patients:

12. A PHASE III STUDY IN POSTMENOPAUSAL WOMEN WITH EARLY BREAST CANCER
PROTOCOL GIM4
LETROZOLE ADJUVANT THERAPY DURATION STUDY (LEAD): STANDARD VERSUS LONG TREATMENT with AROMATASE INHIBITORS
A PHASE III STUDY IN POSTMENOPAUSAL WOMEN WITH EARLY BREAST CANCER

13. Phase III randomized study
Study design
Phase III randomized study
Postmenopausal
TAM 2-3 yrs
LETROZOLE 5 YRS
LETROZOLE 3-2 YRS

14. Study objectives Primary objective: Secondary objectives:
to compare Disease Free Survival (DFS) between treatment groups
Secondary objectives:
to compare Overall Survival (OS)
to compare Safety

15. Study details Start date: 27/07/05 Protocol status: ongoing
Participating centers:
Total randomized patients:

16. PROTOCOL GIM-5 CYPLEC STUDY: CYP19 LETROZOLE CORRELATION STUDY
Letrozole Extended-Adjuvant Therapy After Tamoxifen
Study of Gene CYP19 Correlation with Letrozole Efficacy in Postmenopausal Early Breast Cancer Patients

17. CYPLEC – GIM 5 Multicenter, not comparative, prospective, phase IIIb study of GIM group
Postmenopausal pts
ER and/or PgR +
Tamoxifen
4,5-6 yrs.
Letrozole
5 years
Registration
Total Patients: 2400 during a 3-year period
Primary objective: correlation between a Single Nucleotide
Polymorphism (SNP) of CYP19 and Disease Free Survival (DFS)
Hypothesis: 86% of power to detect a relative reduction of relapse
of 46%: 4-yrs DFS for TC genotype = 91%
4-yrs DFS for CC or TT genotype = 95%

18. Study objectives PRIMARY OBJECTIVE SECONDARY OBJECTIVES
Correlation DFS - SNP of CYP19 gene
SECONDARY OBJECTIVES
Correlation SNP of CYP19 gene and:
1) letrozole plasma concentration
2) aromatase inhibition by plasma estrone-S
3) OS
4) Safety

19. Study details Start date: 27/07/05 Protocol status: ongoing
Participating centers:
Total enrolled patients:

20. A randomized phase III multicenter study
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

21. Randomized phase III study
Study design
Randomized phase III study
Age <45 yrs
Stage I-II-III
Candidate for chemotherapy
Only CT
CT + Triptorelin

22. Study Objectives Primary objective: Secondary objective:
to evaluate efficacy of Triptorelin to prevent chemotherapy-induced amennorreha
Secondary objective:
to compare safety of chemotherapy associated to Triptorelin vs only chemotherapy

23. Study details Start date: 29/05/2003 Protocol status: ongoing
Participating Centers:
Total randomized patients: