Transcript SARC 005: Adjuvant treatment of high risk uterine LMS with gemcitabine/docetaxel followed

SARC 005:
Adjuvant treatment of high risk
uterine LMS with
gemcitabine/docetaxel followed
by doxorubicin: a phase II multicenter trial
PI: Martee L. Hensley, MD
Objectives:
• Determine 2-year PFS among women with
uterine LMS treated with gem-doce, followed
by doxorubicin
• Determine tolerability/toxicity
• Explore predictors of PFS: age, tumor size,
grade, serosal involvement, STS stage v.
FIGO stage, mitotic rate, ER, PR,
menopausal status at dx
Schema
Gemcitabine 900 mg/m2 over 90 minutes days 1, 8
Docetaxel 75 mg/m2 day 8
q 3 wk x 4 cycles
Repeat CT scan
Doxorubicin 60 mg/m2 q 3 w x 4
Repeat CT scan within 6 weeks after
CT c/a/p every 3 mo for 2 y, then every 6 mo
Eligibility
• > 18 years
• FIGO stage I or II, high grade
LMS s/p hysterectomy (uterinelimited disease with pathology
showing serosal involvement IS
eligible even though this is FIGO
IIIA)
• <12 weeks from surgery
• NED by CT within 3 weeks of
enrollment
• Good marrow, kidneys, liver
• No other cancer within 5
years
• No prior gem, doce, or dox
• No prior pelvic RT
• No current HRT or antihormone therapy
• EF > 50%
Correlative studies
• Provide tumor details: size, serosal disease,
mitotic rate
• Provide patient details: age, menopausal
status at dx and at start of adjuvant therapy
• Send unstained slides to MSKCC
- ER and PR
- Site paid $75 when slides are received
Statistical issues
• Target accrual 45 patients
• Bayesian model for continuous assessment
of PFS and safety
• Accrue at least 15 patients per year
• Stop early if data suggest 2 year PFS will be
no better than 30%
Calculating futility
• Event: death or evidence of progression
• Stop if number of events is too many for the
total patient-disease-free-days-on study:
Number of events
Minimum total patient-days
1
0
2
0
3
408
4
920
5
1435
6
1955
7
2477
8
3003
Data capture and management
• On line SARC registration
• On line data entry
• On line CRFs—easy to use
- All grade 3 and 4
- Selected grade 2 (neurological,
hypersensitivity, pulmonary)
• Data monitored by SARC
• Some detail for management plan after recurrence
• Vital status after recurrence every 6 months
Milestones
• Full protocol written, reviewed, approved by
SARC, industry sponsors
• Contracts between SARC and Lilly, SARC
and Sanofi-Aventis are completed
• Gemcitabine and docetaxel both supplied
• Drug distribution from SARC via Biologics to
institutions
Milestones
• Protocol IRB-approved, contracts, etc:
MSKCC, WCI, DFCI
• Several recent IRB approvals, contracts
pending: U Mich, Penn, Moffitt
Results
First accrual: 13 February 2006
• Accrual to date: 7
- MSKCC
5
- Univ Wash
2
• Events = 0
• 3 patients have completed all planned therapy
• Progression-free days = 1063
Results: toxicity
Grade 3 heme tox: 1 patient
Grade 4 heme tox: 1 patient
No pulmonary toxicity
No patients off study for toxicity
For discussion:
• Any barriers to opening study?
• Any accrual difficulties?
• Any unexpected treatment difficulties?
Next steps:
• Treatment likely to be safe, deliverable as adjuvant,
sequential therapy
• Assuming the 2-year PFS is as targeted, SARC
should start to design the phase III trial
• Major issue: “Control” arm that is reasonable and
accruable
–
–
–
–
Pelvic RT? (would likely appeal to Gyn Onc/GOG)
Observation? (would be hard to accrue)
Short-term biologic? (no good rationale)
Short-term single agent chemo? (not a real control, and
might wash out any difference)