Nab-Paclitaxel Sviluppi Futuri nel Carcinoma Mammario.
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nab-Paclitaxel
Sviluppi Futuri nel Carcinoma Mammario
Trial Description Country Phase
A multicenter phase II trial of nab-paclitaxel and Capecitabine as first line treatment in HER2 negative metastatic breast cancer
ITALY II
A phase II, open-label, non-randomized study of nab-paclitaxel for patients with stage II and III luminal breast cancer as neo-adjuvant treatment
SPAIN II
A Randomized Phase III Trial Comparing Nanoparticle-based Paclitaxel With Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Patients With Early Breast Cancer (Gepar Septo)
GERMANY III
Adjuvant phase III trial to compare intense dose-dense treatment with EnPC to dose-dense, tailored therapy with dtEC-dtD for patients with high-risk primary breast cancer
GERMANY III
nab-Paclitaxel Studi Europei Ongoing
Trial Description Country Phase
Neoadjuvant chemotherapy with nab-paclitaxel in women with HER2-negative high-risk breast cancerETNA
ITALY III
A randomized phase II study evaluating three different schedules of nab-paclitaxel as first line chemoterapy in metastatic breast cancerSNAP
ITALY II
A randomized phase II study to evaluate the efficacy and impact on function of two different doses of nab-paclitaxel in elderly patients with advanced breast cancerEFFECT
ITALY II
nab-Paclitaxel Studi “Ready to start”
A multicenter phase II trial of nab-paclitaxel and Capecitabine as first line treatment in HER2 negative Metastatic Breast Cancer
Primary endpoint: The efficacy of combination in terms of response rate (RR) according to RECIST criteria The progression free survival (PFS)Secondary endpoints: Overall survival (OS)Tolerability and safety of the combination regimen according to CTC criteria
Studio GOIM
bid, twice daily; IV, intravenous; MBC, metastatic breast cancer; q3w, every 3 weeks.
Nab-paclitaxel 150 mg/m2 IV in 30 min
GG 1-8 q3w
N = fino a 94Pazienti con ECOG PS 0-1, HER2-, inclusi TN, adeguata funzionalità d’organo6 cicli (+ 2 a discrezione del clinico)
N = fino a 94Pazienti con ECOG PS 0-1, HER2-, inclusi TN, adeguata funzionalità d’organo6 cicli (+ 2 a discrezione del clinico)
Studio GOIM Disegno dello Studio
+Capecitabina
825 mg/m2 Orale bidGG 1-14 q3w
Study GEICAM is a multicenter, open label, non-randomized phase 2 trial to evaluate the efficacy and safety of nab-Paclitaxel in the neoadjuvant treatment of ER positive HER2 negative patients amenable to receive neoadjuvant chemotherapy
Primary endpoint: Determine percentage of patients with poor response in contrast to good response (residual cancer burden)Secondary endpoints: pCRR after surgery, Clinical response (RECIST), Invasive disease-free survival, Correlation of Ki67, gp-60, caveolin-1, SPARC and PAM50 gene expression assay with efficacy, Tolerability
Studio GEICAM A phase II, open-label, non-randomized study of nab-paclitaxel for patients with
stage II and III luminal breast cancer as neo-adjuvant treatment
Studio GEICAM Disegno dello studio
A randomized phase III trial comparing nanoparticle-based paclitaxel with solvent-based paclitaxel as part of neoadjuvant chemotherapy for patients with early breast cancer
Studio GeparSepto
Primary endpoint: To compare pCR rates of neo-adjuvant treatment with nab-paclitaxel with solvent-based paclitaxelSecondary endpoints: Assess the pCR rates for stratified subgroups, Assess various pCR rates, Determine response rates of breast tumor and axillary nodes, Clinical remission rate by taxane use, Rate of breast conservative surgery, Toxicity and compliance, Determine pCR and LRFS in patients with a cCR and a negative core biopsy before surgery
GeparSepto Disegno dello Studio
12 weeks 12 weeksN = 1.200 R
Stratification:
- Subgroup HER2/HR - Ki67 - SPARC
Paclitaxel80 mg/m2 weekly
nab-Paclitaxel150 mg/m2 weekly
Epirubicin 90 mg/m2
Cyclophosphamide 600 mg/m2
If HER2-positive:
Trastuzumab 8 mg/kg (loading dose) followed by 6 mg/kg
Pertuzumab 840 mg (loading dose) followed by 420 mg
if HER2-positive:Trastuzumab
if HR-positive:Tamoxifen, Aromatase-Inhibitor
According to AGO recommendation
Core biopsy Core biopsyCore biopsy
Studio GeparSepto Disegno dello studio
Studio GAIN II
Adjuvant phase III trial to compare intense dose-dense treatment with EnPC to dose-dense, tailored therapy with dtEC-dtD for patients with high-risk primary breast cancer
Primary endpoint: Invasive disease free survival (IDFS)Secondary endpoints: DDFS and OS, Brain metastasis free survival (in the subgroups of TNBC and HER2+ breast cancer patients), Compliance and safety, Quality of life
GAIN II Disegno dello Studio
Epirubicin 150mg/m2 q2w nab-Paclitaxel q2w Cyclophosphamide 2g /m2 q2w(Definition of dose by run-in Phase)
E
C C C C
E E E®
EC 90/600 mg/m², q2w x 4 Docetaxel 75 mg/m², q2w x 4 tailored tailored
D D D D
E E CE nP nPnP C C
R
+1week break
Pegfilgrastim q2w, Epoetin (Darbepoetin-α, Epoetin-β)
Pegfilgrastim q2w, Epoetin (Darbepoetin-α, Epoetin-β)
N=2.886
Adapted from STRATEGIES for SELECTING THERAPY in HERNEGATIVE BREAST CANCER, ESMO Vienna 2012, prIME Oncology activity Satellite Symposium
Studio ETNANeoadjuvant chemotherapy with nab-paclitaxel in women with HER2-negative high-risk breast cancer
Adapted from STRATEGIES for SELECTING THERAPY in HERNEGATIVE BREAST CANCER, ESMO Vienna 2012, prIME Oncology activity Satellite Symposium
Studio ETNA
Adapted from STRATEGIES for SELECTING THERAPY in HERNEGATIVE BREAST CANCER, ESMO Vienna 2012, prIME Oncology activity Satellite Symposium
ETNADisegno dello Studio
A randomized phase II study evaluating three different schedules of nab-paclitaxel in metastatic breast cancer
Primary endpoint: Progression Free Survival (PFS)Secondary endpoints: Adverse events according to CTCAE v4Feasibility: completing treatment according to the protocol for at least 24 weeksDisease control: stable disease for ≥24 weeks or confirmed overall partial response or complete responseOverall survival: time from randomization to death from any cause
Studio SNAP
SNAP Disegno dello Studio
• Randomization allocation 1:1:1 (A:B:C)• Note that the schedules of 150 mg/m2 differ in induction (days 1,8,15) and
maintenance arm B (days 1,15)• nab-paclitaxel administered in 28 day cycles• Continue treatment until progressive disease (PD) or unacceptable toxicity
nab-pac- 75 mg/m2 days 1,8,15,22
N=240
C
Studio EFFECT
A randomized phase II study to evaluate the EFficacy and impact on Function of two different doses of nab-paclitaxEl in elderly patients with advanCed breasT cancer
Primary endpoint: Event-free survival (EFS) where an event is either disease progression or death or decline in functional statusSecondary endpoints: Objective response rate (ORR)Clinical benefit rate (CBR)Progression free survival (PFS)Overall survival (OS)Incidence of Adverse events (defined by CTCAE v4.0)
EFFECT Disegno dello Studio
nab-paclitaxel 125 mg/m2day 1, 8, 15 q 28
nab-paclitaxel 100mg/m2day 1, 8, 15 q 28
R
till disease progression or toxicityStratification factors: age 65-74 vs ≥ 75 yrs diabetes yes, no G3-4 CIRS yes, no IADL deficient yes, no
Age ≥ 65 Locally recurrent or metastatic HER2-neg breast cancer or HER2- positive but considered not eligible for anti-HER2 therapyNo prior CT for advanced breast cancerMeasurable or evaluable disease
N=156
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