Transcript Current Protocols of the Radiation Therapy Oncology Group Montreal, Quebec

Current Protocols of the
Radiation Therapy Oncology
Group
Montreal, Quebec
Nov. 12, 2004
Phase II Trial (RTOG S-0132):
Study Design
SD/PR
Resectable
GIST
(candidate for
neoadjuvant
therapy)
Neoadjuvant
imatinib mesylate
(600 mg/d,
8 wk)
PD
R
E
S
E
C
T
I
O
N
Adjuvant
imatinib
mesylate
(600 mg/d,
PO 2 y)
Follow
for
PFS
R
E
S
E
C
T
I
O
N
Off study
Phase II Trial (RTOG S-0132):
Eligibility
Potentially resectable primary tumors
> 5cm
Potentially resectable metastatic
tumors > 2 cm
C-Kitt expression must be
documented
Phase II Trial (RTOG S-0132):
Study Design* (Cont’d)
Objectives:
Treatment:
Inclusion:
*Trial ongoing.
Primary:
PFS with imatinib mesylate in adjuvant
setting
Secondary:
Response rate in neoadjuvant
setting
Compare CT and PET responses
in neoadjuvant setting
Safety in adjuvant setting
Imatinib mesylate 600 mg/d
Present with KIT-positive malignant GIST
No extra-abdominal disease
Imatinib mesylate–naive
No prior therapy 28 days before entry
RTOG 0132
Biological Correlates Before and After Gleevec:
A. Fixed Tissue
– KIT mutational analysis
– Glut 4 expression correlation with PET SUV
B. Frozen Tissue
Global genomic array to evaluate
differential gene expression before
and after Gleevec
Evaluation of phosphorylation
of intermediate signaling molecules
within the KIT activation pathway
RTOG 0132: Status of Protocol
• Protocol opened February 28, 2002
• Accrual goal is 65 patients
• Accrual as of Oct. 26, 2004 is 35 patients
A Pilot Phase II Study Of Pre-operative Radiation
Therapy And Thalidomide For Low Grade Primary Soft
Tissue Sarcoma Or Pre-operative
Maid/thalidomide/radiation Therapy For
High/intermediate Grade Primary Soft Tissue Sarcoma
Of The Extremity Or Body Wall
RTOG 0330
Rationale for Thalidomide
• immunomodulatory agent
• antiangiogenic properties
– potential relationship to circulating levels of
bFGF and VEGF
– these appear to be elevated in patients with
STS
• frequently used in combination therapy
• well tolerated
• oral agent
RTOG 0330: Eligibility for
Cohort A
• Cohort A : tumor > 8.0 cm in maximal
diameter and intermediate to high grade
• Normal heart function (EF ≥ 50%)
• Accrual goal is 22 patients
RTOG 0330: Cohort A
• based upon experience with RTOG 9514
additional new questions/endpoints
– toxicity issues of 9514 & with Thalidomide
– benefit of addition of agent with alternative
mechanism of action
– biologic endpoints
– response (clinical response & necrosis on
central pathology review)
RTOG 0330: Cohort A
Biopsy & submission to central
pathology, Blood draws x 6
RT: 22 Gy/course, 44 Gy total
Thalidomide 200 mg/day for
1 year
Thalidomide
RT
Surgery
RT
MAID
MAID
Diagnosis & Registration
Accrual goal 22 patients
Day 80
MAID
MAID
RT: 16 Gy for + margins
RTOG 0330: Translational Studies
(an Abbreviated List)
Paraffin Blocks from Biopsy and Resections
• Microvessel Density
• Biological /Prognostic Markers
– uPA/ tPA/ PAI-1
• EGFR, p53, Ki-67,Tunel
Studies on Circulating Factors Using WB
• VEGF and bFGF
• Circulating endothelial cells (CEC)
RTOG 0330: Eligibility Cohort B
• Low grade STS (Grade 1 or 2) and > 5 cm
in diameter in greatest dimension.
• Accrual goal is 22 patients.
RTOG 0330: Cohort B
RT 50 Gy in 5
weeks
Thalidomide
200mg/day
22 patients
Surgery
Thalidomide 200mg/day for
6 months
RTOG 0330: Translational Studies
(an Abbreviated List)
Paraffin Blocks from Biopsy and Resections
• Microvessel Density
• Biological /Prognostic Markers
– uPA/ tPA/ PAI-1
• EGFR, p53, Ki-67,Tunel
Studies on Circulating Factors Using WB
• VEGF and bFGF
• Circulating endothelial cells (CEC)
RTOG 0330: Status
• CTEP Approved and open for 3 months
• Open at 5 centers
• No patients accrued