Transcript Document

Gynecologic Oncology Group
Uterine Corpus Trials: GCIG
David Scott Miller, M.D., F.A.C.O.G., F.A.C.S.
Director and Dallas Foundation Chair in Gynecologic Oncology
Professor of Obstetrics & Gynecology
University of Texas Southwestern Medical Center
Dallas, Texas, U.S.A.
Gynecologic
Oncology
Group
PHASE III TRIAL OF PELVIC RADIATION THERAPY
VERSUS VAGINAL CUFF BRACHYTHERAPY
FOLLOWED BY PACLITAXEL/CARBOPLATIN
CHEMOTHERAPY IN PATIENTS WITH HIGH RISK,
EARLY STAGE ENDOMETRIAL CANCER
GOG 0249
Eligible:
•Stage I-IIA endometrial
carcinoma, with highintermediate risk factors
•Stage IIB (occult)
endometrial carcinoma
(any histology), with or
without risk factors
•Stage I-IIB (occult)
serous or clear cell
endometrial carcinoma,
with or without other risk
features
R
A
N
D
O
M
I
Z
E
Regimen I:
•Pelvic Radiation Therapy (4500/25 fractions-5040 cGy/28 fractions)
over 5-6 weeks
•Optional Vaginal Cuff Boost ONLY for Stage II patients and Stage I
patients with papillary serous and clear cell carcinomas
Regimen II:
•Vaginal Cuff Brachytherapy + 3 cycles of chemotherapy* consisting of:
•Paclitaxel 175 mg/m2 (3hr) + Carboplatin AUC 6 q 21 days
*To start within 3 weeks of initiating brachytherapy
Gynecologic
Oncology
Group
GOG0249
• Objectives
–
–
–
–
Recurrence free survival
Survival
Patterns of failure
QOL
• Stats
– 49% decrease in recurrence/death
– 85% > 92% 3 yr RFS
– N = 562
• Activated 23 Mar 2009
Gynecologic
Oncology
Group
Uterine Corpus Committee
0184R
• GOG0258 (UC0704): A Randomized
Phase III Trial of Cisplatin and Tumor
Volume Directed Irradiation Followed by
Carboplatin and Paclitaxel vs. Carboplatin
and Paclitaxel for Optimally Debulked,
Advanced Endometrial Carcinoma
Gynecologic
Oncology
Group
GOG258
Surgical debulking; optimal
Stage III and IVA
Register and randomize
ARM 1
XRT 45Gy
Cisplatin 50mg/m2 D1 and D28
Vaginal brachytherapy
ARM 2
Carboplatin AUC 6
Paclitaxel 175mg/m2 q3weeks X6
Carboplatin AUC 6
Paclitaxel 175mg/m2 q3weeks X4
Gynecologic
Oncology
Group
GOG0258
• Objectives
– Recurrence free survival
– Survival
– Adverse effects
• Stats
– 28% decrease recurrence/death
– 61% > 70% 3 yr RFS
– N = 804
Gynecologic
Oncology
Group
Uterine Corpus Committee
Pelvic Recurrence
• 33 + 99 has resulted in:
– TAH-BSO lymphadenectomy alone
– fewer using adjuvant WPRT
• GOG0238: A Randomized Trial of Pelvic
Irradiation With or Without Concurrent
Weekly Cisplatin in Patients With PelvicOnly Recurrence of Carcinoma of the
Uterine Corpus
Gynecologic
Oncology
Group
GOG
0238
Gynecologic
Oncology
Group
GOG0238
• Objectives
– PFS
– Sites of recurrence
– OS
• Stats
–
–
–
–
Phase II-III
Interim analysis > 60 failures
Opened Feb ‘08
N = 164
Gynecologic
Oncology
Group
Uterine Corpus Committee
150R & 161R
• GOG0261 (UC0701): Randomized Phase
III Trial of Carboplatin plus Paclitaxel
versus Ifosfamide plus Taxol in Patients
with Advanced, Persistent or Recurrent
Carcinosarcoma
Gynecologic
Oncology
Group
GOG0261
• Stage I-IV,
Persistent or
Recurrent
Carcinosarcoma
(chemotherapynaïve)
• Patients may have
prior pelvic and/or
vaginal radiation
therapy
Translational Research
requirements include an
archival formalin-fixed and
paraffin-embedded tumor
specimen and a pretreatment whole blood
specimen as described in
Section 7.2
Stratification:
• History of Pelvic
Radiation
• Disease Status/
Stage at time of
Study registration
• Measurable
Disease
R
A
N
D
O
M
I
Z
E
Quality of Life assessments
required at: Baseline;
approximately week 6 (prior
to cycle 3); week 15 (prior to
cycle 6); week 26 post
initiation of therapy. See
section 7.3 for details.
REGIMEN I:
Paclitaxel 175 mg/m²* IV over 3
hours day 1
Carboplatin (AUC=6*) IV day 1
Repeat q 3 weeks x6 cycles
G-CSF
Support:
REGIMEN II:
Ifosfamide 1.6 g/m²** IV days 1, 2, 3
Mesna***
Paclitaxel 135 mg/m² by 3 hour
infusion on day 1
Repeat q 3 weeks x6 cycles
Filgrastim or
Pegfilgrastim
beginning day 4-6
(see Section 5.22.)
*Initial dose reduced to
Paclitaxel 135 mg/m² and
Carboplatin (AUC=5) if prior
whole pelvic radiotherapy
** Initial dose reduced to
Ifosfamide 1.2 g/m²/day x day
days if prior whole pelvic
radiotherapy
*** See Sec. 5.22 for Mesna
administration information.
Gynecologic
Oncology
Group
GOG261
• Objectives
–
–
–
–
OS
PFS
Toxicity
QOL
• Stats
– Noninferiority
– Death rate < 11%
– N = 415, (264 deaths)
Gynecologic
Oncology
Group
Concept
Biweekly dactinomycin now needs to be
tested against 8-day MTX/FAR, arguably
the most commonly used regimen
worldwide. The 8-day regimen has a
similar primary response but a vastly
different cost, resource and utility profile,
and it has never been subjected to the
scrutiny of a multi-centred RCT.
Gynecologic
Oncology
Group